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Vinorelbine With Trastuzumab Emtansine in Pre-Treated HER2-Positive Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT02658084
Recruitment Status : Terminated (Terminated due to low accrual and toxicity concerns.)
First Posted : January 18, 2016
Results First Posted : April 17, 2019
Last Update Posted : April 17, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Reshma Mahtani, University of Miami

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Cancer
Metastatic Breast Cancer
Interventions Drug: Vinorelbine
Drug: Trastuzumab Emtansine
Enrollment 2
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1: T-DM1 + Vinorelbine Phase 2: T-DM1 + RP2D Vinorelbine
Hide Arm/Group Description

One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Period Title: Overall Study
Started 2 0
Completed 0 0
Not Completed 2 0
Reason Not Completed
Withdrawal by Subject             1             0
Study Termination             1             0
Arm/Group Title Phase 1: T-DM1 + Vinorelbine Phase 2: T-DM1 + RP2D Vinorelbine Total
Hide Arm/Group Description

One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Total of all reporting groups
Overall Number of Baseline Participants 2 0 2
Hide Baseline Analysis Population Description
Only Phase 1 enrolled participants, however, the study was terminated early. The Phase 2 arm did not open to accrual.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 0 participants 2 participants
<=18 years
0
   0.0%
0
0
   0.0%
Between 18 and 65 years
2
 100.0%
0
2
 100.0%
>=65 years
0
   0.0%
0
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 0 participants 2 participants
Female
2
 100.0%
0
2
 100.0%
Male
0
   0.0%
0
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 0 participants 2 participants
American Indian or Alaska Native
0
   0.0%
0
0
   0.0%
Asian
0
   0.0%
0
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
0
   0.0%
Black or African American
1
  50.0%
0
1
  50.0%
White
1
  50.0%
0
1
  50.0%
More than one race
0
   0.0%
0
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants 0 participants 2 participants
2 2
1.Primary Outcome
Title Phase 1 - Maximum Tolerated Dose (MTD) of Vinorelbine in Combination With a Fixed Dose of Trastuzumab Emtansine.
Hide Description Identifying the Maximum Tolerated Dose (MTD) of Vinorelbine combined with a fixed dose of Trastuzumab Emtansine to be recommended for the phase II portion of the study (RP2D).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Approximately 15 to 21 participants would be needed to establish the recommended phase II dose (RP2D). Only 2 participants were enrolled therefore the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) were not determined.
Arm/Group Title Phase 1: T-DM1 + Vinorelbine
Hide Arm/Group Description:

One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Phase 2 - Rate of Progression-Free Survival (PFS)
Hide Description Rate of Progression-Free Survival (PFS) in participants receiving the RP2D of vinorelbine in combination with Trastuzumab Emtansine therapy. PFS is defined as the time from date from first treatment received on study until documented disease progression or death (by any cause, in the absence of progression). In progression-free patients, PFS will be censored at the last evaluable tumor assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Arm/Group Title Phase 2: T-DM1 + RP2D Vinorelbine
Hide Arm/Group Description:

One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Primary Outcome
Title Phase 1 - Rate of Participants Experiencing Adverse Events
Hide Description Rate of participants experiencing adverse events including dose-limiting toxicities (DLTs) and serious adverse events (SAEs).
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
For adverse events, participants who received at least one dose of study therapy. For dose-limiting toxicities, participants who experienced a dose-limiting toxicity during the first two cycles of study therapy.
Arm/Group Title Phase 1: T-DM1 + Vinorelbine
Hide Arm/Group Description:

One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: participants
Dose-limiting toxicities (DLTs) 2
Adverse events (AEs) 2
4.Secondary Outcome
Title Phase 2 - Clinical Benefit Rate (CBR)
Hide Description Rate of participants achieving best overall response of complete response (CR), partial response (PR) or stable disease (SD) for >/= 6 months on protocol therapy, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Arm/Group Title Phase 2: T-DM1 + RP2D Vinorelbine
Hide Arm/Group Description:

One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Phase 2 - Overall Survival (OS) Rate
Hide Description Overall Survival (OS) is defined as the elapsed time from date from first treatment received on study to death or date of censoring. Patients alive or those lost to follow-up will be censored at the last date of contact (or last date known to be alive).
Time Frame Up to 5 Years
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Arm/Group Title Phase 2: T-DM1 + RP2D Vinorelbine
Hide Arm/Group Description:

One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Phase 2 - Objective Response Rate (ORR)
Hide Description Rate of participants achieving a best overall response of complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 criteria.
Time Frame Up to 5 Years
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Arm/Group Title Phase 2: T-DM1 + RP2D Vinorelbine
Hide Arm/Group Description:

One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 18 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1: T-DM1 + Vinorelbine
Hide Arm/Group Description

One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).

Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.

Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.

All-Cause Mortality
Phase 1: T-DM1 + Vinorelbine
Affected / at Risk (%)
Total   0/2 (0.00%)    
Hide Serious Adverse Events
Phase 1: T-DM1 + Vinorelbine
Affected / at Risk (%) # Events
Total   2/2 (100.00%)    
Cardiac disorders   
Chest pain - cardiac  1  1/2 (50.00%)  1
Gastrointestinal disorders   
Abdominal pain  1  2/2 (100.00%)  2
Constipation  1  1/2 (50.00%)  1
Dyspepsia  1  1/2 (50.00%)  1
Gastroparesis  1  1/2 (50.00%)  1
Nausea  1  1/2 (50.00%)  1
Vomiting  1  1/2 (50.00%)  1
General disorders   
Fatigue  1  2/2 (100.00%)  2
Pain  1  1/2 (50.00%)  1
Metabolism and nutrition disorders   
Anorexia  1  1/2 (50.00%)  1
Hypokalemia  1  1/2 (50.00%)  1
Hypomagnesemia  1  1/2 (50.00%)  1
Hypophosphatemia  1  1/2 (50.00%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/2 (50.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1: T-DM1 + Vinorelbine
Affected / at Risk (%) # Events
Total   2/2 (100.00%)    
Blood and lymphatic system disorders   
Hypercapnia  1  1/2 (50.00%)  1
Hypochloremia  1  1/2 (50.00%)  1
Gastrointestinal disorders   
Abdominal pain  1  1/2 (50.00%)  1
Constipation  1  1/2 (50.00%)  1
Diarrhea  1  1/2 (50.00%)  1
Dyspepsia  1  1/2 (50.00%)  1
Nausea  1  2/2 (100.00%)  2
Stomach pain  1  1/2 (50.00%)  1
Vomiting  1  1/2 (50.00%)  1
General disorders   
Chills  1  1/2 (50.00%)  1
Fatigue  1  2/2 (100.00%)  6
Fever  1  1/2 (50.00%)  1
Flu like symptoms  1  1/2 (50.00%)  1
Investigations   
Alanine aminotransferase increased  1  2/2 (100.00%)  2
Platelet count decreased  1  2/2 (100.00%)  3
Metabolism and nutrition disorders   
Anorexia  1  2/2 (100.00%)  2
Aspartate aminotransferase increased  1  2/2 (100.00%)  3
Dehydration  1  1/2 (50.00%)  1
Hypokalemia  1  1/2 (50.00%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/2 (50.00%)  1
Nervous system disorders   
Dizziness  1  1/2 (50.00%)  1
Lethargy  1  1/2 (50.00%)  1
Somnolence  1  1/2 (50.00%)  1
Psychiatric disorders   
Anxiety  1  1/2 (50.00%)  1
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  1/2 (50.00%)  1
Epistaxis  1  1/2 (50.00%)  1
Nasal congestion  1  1/2 (50.00%)  1
Vascular disorders   
Hypertension  1  1/2 (50.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Early study termination by mutual decision of the Sponsor and the Investigator due to lower than expected accrual and toxicities concerns. Only the Phase 1 arm opened to accrual; Phase 2 did not open to accrual.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Reshma Mahtani
Organization: University of Miami
Phone: 954-698-3639
EMail: rmahtani@miami.edu
Layout table for additonal information
Responsible Party: Reshma Mahtani, University of Miami
ClinicalTrials.gov Identifier: NCT02658084    
Other Study ID Numbers: 20151055
First Submitted: January 14, 2016
First Posted: January 18, 2016
Results First Submitted: March 18, 2019
Results First Posted: April 17, 2019
Last Update Posted: April 17, 2019