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Trial record 39 of 173 for:    pertuzumab

Phase II Study of Eribulin Mesylate, Trastuzumab, and Pertuzumab in Women With Metastatic, Unresectable Locally Advanced, or Locally Recurrent HER2-Positive Breast Cancer

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ClinicalTrials.gov Identifier: NCT01912963
Recruitment Status : Terminated (The study terminated early due to weak accrual.)
First Posted : July 31, 2013
Results First Posted : December 5, 2018
Last Update Posted : December 5, 2018
Sponsor:
Collaborators:
Eisai Inc.
Genentech, Inc.
Information provided by (Responsible Party):
Rachel Freedman, MD, MPH, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HER2-positive Breast Cancer
Metastatic Breast Cancer
Interventions Drug: Pertuzumab
Drug: Trastuzumab
Drug: eribulin
Enrollment 32
Recruitment Details Participants enrolled from September 2013 through May 2016.
Pre-assignment Details  
Arm/Group Title Phase I: Dose Level 1 (D1) Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1)

Cycle duration=21 days

The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab

Trastuzumab

eribulin

Period Title: Overall Study
Started 6 19 7
Completed [1] 0 0 0
Not Completed 6 19 7
Reason Not Completed
Disease Progression (RECIST1.1)             6             9             5
Disease Progression (not RECIST1.1)             0             7             1
Adverse Event             0             1             1
Withdrawal by Subject             0             1             0
Sought treatment locally             0             1             0
[1]
Since treatment was not of fixed duration, all participants were considered 'Not Completed'.
Arm/Group Title Phase I: Dose Level 1 (D1) Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure Total
Hide Arm/Group Description

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1)

Cycle duration=21 days

The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab

Trastuzumab

eribulin

Total of all reporting groups
Overall Number of Baseline Participants 6 19 7 32
Hide Baseline Analysis Population Description
The analysis dataset is comprised all enrolled patients.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 19 participants 7 participants 32 participants
55
(38 to 66)
53
(33 to 73)
47
(40 to 70)
53
(33 to 73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 19 participants 7 participants 32 participants
Female
5
  83.3%
19
 100.0%
7
 100.0%
31
  96.9%
Male
1
  16.7%
0
   0.0%
0
   0.0%
1
   3.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 19 participants 7 participants 32 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
  10.5%
0
   0.0%
2
   6.3%
White
6
 100.0%
14
  73.7%
7
 100.0%
27
  84.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
3
  15.8%
0
   0.0%
3
   9.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Count of participants
United States Number Analyzed 6 participants 19 participants 7 participants 32 participants
6 19 7 32
Time from Primary Diagnosis to metastatic diagnosis  
Measure Type: Number
Unit of measure:  Count of participants
Number Analyzed 6 participants 19 participants 7 participants 32 participants
< 2 years 1 5 4 10
> 2 years 2 8 2 12
Metastatic diagnosis at primary diagnosis 3 6 1 10
ECOG PS   [1] 
Measure Type: Number
Unit of measure:  Count of participants
Number Analyzed 6 participants 19 participants 7 participants 32 participants
ECOG PS 0 5 14 4 23
ECOG PS 1 1 4 3 8
Unknown 0 1 0 1
[1]
Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0: Fully active, able to carry on all pre-disease performance without restriction ECOG PS 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature ECOG PS 2: Ambulatory and capable of all self-care but unable to carry out any work activities; Up and about more than 50% of waking hours
1.Primary Outcome
Title Eribulin the Recommended Phase II Dose (RP2D) [Phase I]
Hide Description The RP2D of eribulin in combination with pertuzumab and trastuzumab is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The RP2D is defined as the highest dose at which fewer than one-third of six patients experience a DLT. In this Phase I run-in, only 2 dose levels were under evaluation: a starting dose (D1) and a de-escalation dose (D-1) if 2 or more DLTs are observed in Dose Level 1 (DL1).
Time Frame The observation period for the RP2D was the 1st cycle of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised all enrolled Phase I participants.
Arm/Group Title Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1)

Cycle duration=21 days

The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: mg/m^2
1.4
2.Primary Outcome
Title Dose Limiting Toxicity (DLT) [Phase I]
Hide Description A DLT was defined as an adverse event that (a) is deemed by the investigator to be probably or likely related with protocol therapy and (b) occurs during and/or begins during the first cycle of the study treatment, and (c) meets any of the following criteria: grade 4 hematologic toxicity with > 1 week of duration, grade 3 or 4 febrile neutropenia of any duration; or grade 3 or 4 non hematologic toxicity (excluding nausea, vomiting, and alopecia).
Time Frame The observation period for DLTs was the 1st cycle of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I: Pertuzumab, Trastuzumab and Eribulin Dose Level 1 (D1
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1)

Cycle duration=21 days

The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Primary Outcome
Title Objective Response Rate (ORR) [Phase II]
Hide Description The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time Frame Disease was evaluated radiologically at baseline and every 2 or 3 cycles in the treatment and extension phase, respectively. Median (range) treatment duration was 7(2-25) cycles for Cohort A and 4(3-18) cycles for Cohort B.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised all enrolled Phase II patients.
Arm/Group Title Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 19 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.26
(0.09 to 0.51)
0.0
(0.0 to .41)
4.Secondary Outcome
Title Clinical Benefit Rate (CBR) [Phase II]
Hide Description The clinical benefit rate (CBR) was defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.
Time Frame Disease was evaluated radiologically at baseline and every 2 or 3 cycles in the treatment and extension phase, respectively. Median (range) treatment duration was 7(2-25) cycles for Cohort A and 4(3-18) cycles for Cohort B.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 19 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
.316
(.126 to .566)
.143
(.004 to .579)
5.Secondary Outcome
Title Progression-free Survival (PFS) [Phase II]
Hide Description Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.(whichever occurs first).
Time Frame Disease was evaluated radiologically at baseline, every 2 or 3 cycles in the treatment and extension phase, respectively, and every 9 weeks post-treatment until disease progression. Median follow-up in this study cohort was 15.6 months (up to 20).
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 19 6
Median (95% Confidence Interval)
Unit of Measure: months
6.9
(3.5 to 11)
3 [1] 
(2.1 to NA)
[1]
The upper confidence limit was not estimable based on the Kaplan-Meier method because of insufficient follow-up.
6.Secondary Outcome
Title Overall Survival (OS) [Phase II]
Hide Description Overall survival (OS) is defined as the time from the date of registration to the date of death, or censored at the date the participant was last known alive. OS is estimated based on the Kaplan-Meier method.
Time Frame In long-term follow-up, participants were followed for survival every 6 months up to 1 year after treatment discontinuation. Median follow-up in this study cohort was 15.6 months (up to 20).
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 19 6
Median (95% Confidence Interval)
Unit of Measure: months
13.9 [1] 
(11.2 to NA)
7.4 [1] 
(5.7 to NA)
[1]
The upper confidence limit was not estimable based on the Kaplan-Meier method because of insufficient follow-up.
7.Secondary Outcome
Title Grade 4 Treatment-Related Toxicity Rate
Hide Description Grade 4 treatment-related toxicity rate is the percentage of participants experiencing at least one treatment-related grade 4 adverse event (AE) of any type during the time of observation as reported on case report forms. 'Treatment-related' is a treatment attribution of possibly, probably or definite based on the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.
Time Frame AEs were assessed every cycle on treatment. Median (range) treatment duration was 7(2-25) cycles for Cohort A and 4(3-18) cycles for Cohort B.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 19 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.5
(1.29 to 33.1)
14.3
(0.4 to 57.9)
8.Post-Hoc Outcome
Title 1-year Overall Survival
Hide Description 1-year overall survival is the probability of patients remaining alive 1 year from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up.
Time Frame In long-term follow-up, participants were followed for survival every 6 months up to 1 year after treatment discontinuation. Median follow-up in this study cohort was 15.6 months (up to 20).
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description:

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Overall Number of Participants Analyzed 19 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability
61.1
(42.3 to 88.3)
50
(22.5 to 100)
Time Frame Adverse events (AEs) were assessed each cycle throughout treatment from time of first dose and until outstanding adverse events are stable or resolved, if any. Median treatment duration (and thus average period for AE assessment) was 11.5 cycles, 7 cycles, 4 cycles for D1, Cohort A, Cohort B, respectively. Maximum treatment duration was 26 cycles, 25 cycles, 18 cycles for D1, Cohort A, Cohort B, respectively. Cycle length is 21 days/3 weeks.
Adverse Event Reporting Description Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possible, probable or definite and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4. Other AEs included grade 3 or higher events unrelated to treatment and all grade 1-2 events.No further data is available to specify classification of other beyond the general term.
 
Arm/Group Title Phase I: Dose Level 1 (D1) Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Hide Arm/Group Description

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1)

Cycle duration=21 days

The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.

All-Cause Mortality
Phase I: Dose Level 1 (D1) Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/19 (0.00%)   0/7 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Phase I: Dose Level 1 (D1) Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/6 (66.67%)   7/19 (36.84%)   4/7 (57.14%) 
Blood and lymphatic system disorders       
Anemia  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
Febrile neutropenia  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
Gastrointestinal disorders       
Diarrhea  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
Dysphagia  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Esophagitis  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Mucositis oral  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
General disorders       
Fatigue  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Infections and infestations       
Sepsis  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Investigations       
Aspartate aminotransferase increased  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Electrocardiogram QT corrected interval prolonged  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Lymphocyte count decreased  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Neutrophil count decreased  1  3/6 (50.00%)  2/19 (10.53%)  4/7 (57.14%) 
Metabolism and nutrition disorders       
Dehydration  1  0/6 (0.00%)  0/19 (0.00%)  2/7 (28.57%) 
Hypophosphatemia  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Nervous system disorders       
Ataxia  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Peripheral motor neuropathy  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Peripheral sensory neuropathy  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I: Dose Level 1 (D1) Phase II Cohort A: Without Prior Pertuzumab Exposure Phase II Cohort B: With Prior Pertuzumab Exposure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   18/19 (94.74%)   5/7 (71.43%) 
Blood and lymphatic system disorders       
Anemia  1  0/6 (0.00%)  2/19 (10.53%)  2/7 (28.57%) 
Blood and lymphatic system disorders - Other  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Cardiac disorders       
Palpitations  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Ear and labyrinth disorders       
Tinnitus  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Eye disorders       
Cataract  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Watering eyes  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Gastrointestinal disorders       
Abdominal pain  1  0/6 (0.00%)  2/19 (10.53%)  1/7 (14.29%) 
Cheilitis  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Constipation  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
Diarrhea  1  2/6 (33.33%)  7/19 (36.84%)  3/7 (42.86%) 
Dyspepsia  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Dysphagia  1  1/6 (16.67%)  0/19 (0.00%)  1/7 (14.29%) 
Esophagitis  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Mucositis oral  1  2/6 (33.33%)  3/19 (15.79%)  0/7 (0.00%) 
Nausea  1  1/6 (16.67%)  8/19 (42.11%)  2/7 (28.57%) 
Toothache  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Vomiting  1  1/6 (16.67%)  4/19 (21.05%)  0/7 (0.00%) 
General disorders       
Chills  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Edema limbs  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Fatigue  1  0/6 (0.00%)  11/19 (57.89%)  0/7 (0.00%) 
Fatigue  1  6/6 (100.00%)  0/19 (0.00%)  4/7 (57.14%) 
Fever  1  0/6 (0.00%)  0/19 (0.00%)  2/7 (28.57%) 
Flu like symptoms  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Gait disturbance  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Infusion related reaction  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Pain  1  2/6 (33.33%)  2/19 (10.53%)  0/7 (0.00%) 
Infections and infestations       
Bladder infection  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Bronchial infection  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Paronychia  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Rash pustular  1  0/6 (0.00%)  2/19 (10.53%)  0/7 (0.00%) 
Sinusitis  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Skin infection  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Upper respiratory infection  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Urinary tract infection  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  0/6 (0.00%)  2/19 (10.53%)  1/7 (14.29%) 
Aspartate aminotransferase increased  1  0/6 (0.00%)  3/19 (15.79%)  1/7 (14.29%) 
Blood bilirubin increased  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Electrocardiogram QT corrected interval prolonged  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Investigations - Other  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Lymphocyte count decreased  1  0/6 (0.00%)  2/19 (10.53%)  0/7 (0.00%) 
Neutrophil count decreased  1  2/6 (33.33%)  3/19 (15.79%)  0/7 (0.00%) 
Platelet count decreased  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Weight loss  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
White blood cell decreased  1  0/6 (0.00%)  3/19 (15.79%)  0/7 (0.00%) 
Metabolism and nutrition disorders       
Anorexia  1  1/6 (16.67%)  3/19 (15.79%)  0/7 (0.00%) 
Dehydration  1  0/6 (0.00%)  2/19 (10.53%)  1/7 (14.29%) 
Hyperglycemia  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Hypermagnesemia  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Hypoalbuminemia  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Hypoglycemia  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Hypokalemia  1  0/6 (0.00%)  2/19 (10.53%)  1/7 (14.29%) 
Hypomagnesemia  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Hyponatremia  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Hypophosphatemia  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Back pain  1  0/6 (0.00%)  2/19 (10.53%)  0/7 (0.00%) 
Bone pain  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Chest wall pain  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Generalized muscle weakness  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Muscle weakness left-sided  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Muscle weakness lower limb  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Musculoskeletal and connective tissue disorder - Other  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Pain in extremity  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumor pain  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Nervous system disorders       
Ataxia  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Dizziness  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Facial nerve disorder  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Headache  1  0/6 (0.00%)  3/19 (15.79%)  0/7 (0.00%) 
Memory impairment  1  1/6 (16.67%)  0/19 (0.00%)  0/7 (0.00%) 
Peripheral motor neuropathy  1  1/6 (16.67%)  6/19 (31.58%)  1/7 (14.29%) 
Peripheral sensory neuropathy  1  2/6 (33.33%)  6/19 (31.58%)  2/7 (28.57%) 
Tremor  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Psychiatric disorders       
Anxiety  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Depression  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Renal and urinary disorders       
Urinary tract pain  1  0/6 (0.00%)  1/19 (5.26%)  1/7 (14.29%) 
Reproductive system and breast disorders       
Vaginal discharge  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/6 (16.67%)  0/19 (0.00%)  1/7 (14.29%) 
Dyspnea  1  2/6 (33.33%)  0/19 (0.00%)  0/7 (0.00%) 
Pneumonitis  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Respiratory, thoracic and mediastinal disorders - Other, specify  1  0/6 (0.00%)  0/19 (0.00%)  1/7 (14.29%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  1/6 (16.67%)  6/19 (31.58%)  2/7 (28.57%) 
Dry skin  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Nail discoloration  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
Rash acneiform  1  0/6 (0.00%)  2/19 (10.53%)  1/7 (14.29%) 
Rash maculo-papular  1  1/6 (16.67%)  2/19 (10.53%)  0/7 (0.00%) 
Skin and subcutaneous tissue disorders - Other  1  1/6 (16.67%)  1/19 (5.26%)  0/7 (0.00%) 
Vascular disorders       
Hypertension  1  0/6 (0.00%)  1/19 (5.26%)  0/7 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
The study is limited as it was terminated early due to slow accrual.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Rachel Freeman MD
Organization: Dana-Farber Cancer Institute
Phone: 617.632.3000
EMail: Rachel_Freedman@dfci.harvard.edu
Layout table for additonal information
Responsible Party: Rachel Freedman, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01912963     History of Changes
Other Study ID Numbers: 13-163
First Submitted: July 24, 2013
First Posted: July 31, 2013
Results First Submitted: October 8, 2018
Results First Posted: December 5, 2018
Last Update Posted: December 5, 2018