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PF-06671008 Dose Escalation Study in Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02659631
Recruitment Status : Terminated
First Posted : January 20, 2016
Results First Posted : May 6, 2020
Last Update Posted : May 6, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06671008 in patients with advanced solid tumors with the potential to have P-cadherin expression. The study will then expand to look at the selected dose in patients with P-cadherin expressing TNBC, CRC or NSCLC.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: PF-06671008 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06671008 IN PATIENTS WITH ADVANCED SOLID TUMORS
Actual Study Start Date : April 28, 2016
Actual Primary Completion Date : March 29, 2019
Actual Study Completion Date : March 29, 2019

Arm Intervention/treatment
Experimental: PF-06671008 Drug: PF-06671008
Dose Escalation Phase - Part 1

Drug: PF-06671008
Dose Expansion Phase - Part 2




Primary Outcome Measures :
  1. Number of Participants With Dose-Limiting Toxicities (DLTs) - Part 1 [ Time Frame: Baseline through Day 21 (Cycle 1) ]
    DLT was defined as any of the following adverse events occurring in the first cycle of treatment (21 days after the first dose): a) Hematologic: Febrile neutropenia defined as an absolute neutrophil count (ANC) <1.0 x 10^9/L with a single temperature of >38.3°C, or 101°F, or a sustained temperature of >=38°C, or 100.4°F, for more than one hour; b) Non-hematologic: Delay by more than 2 weeks in receiving the next scheduled dose due to persisting treatment related toxicities; c) Any grade 3 or 4 clinically-relevant hematologic or non-hematologic toxicity.

  2. Number of Participants With Objective Response (OR) - Part 2 [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]

    Number of participants with OR based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1.

    CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions.

    PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.



Secondary Outcome Measures :
  1. Maximum Serum Concentration (Cmax) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]

    Maximum serum concentration (Cmax) of PF-06671008 was observed directly from data.

    Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.


  2. Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
    Time for Maximum serum concentration (Tmax) of PF-06671008 was observed directly from data as time of first occurrence.

  3. Terminal Elimination Half-life (t1/2) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]

    Terminal elimination half-life (t1/2) of PF-06671008 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

    Arithmetic mean was not calculated if fewer than 3 participants had reportable parameter values.


  4. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]

    Tau refers to the dosing interval, which was 1 week. Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method.

    Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.


  5. Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]

    AUCinf was calculated as AUClast +(Clast*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

    Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.


  6. Systemic Clearance (CL) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]

    Systemic Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms.

    Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.


  7. Apparent Clearance (CL/F) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]

    Apparent Clearance (CL/F) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arm.

    Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.


  8. Number of Participants With OR - Part 1 [ Time Frame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression, unacceptable toxicity, or up to 24 months ]

    Number of participants with OR based on assessment of CR or PR according to RECIST v1.1.

    CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions.

    PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.


  9. Number of Participants With Progression Free Survival (PFS) - Part 2 [ Time Frame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months ]
    The period from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

  10. Number of Participants With Overall Survival (OS) - Part 2 [ Time Frame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months ]
    The period from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death).

  11. Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008 [ Time Frame: C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months ]
    ADA against PF-06671008 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer >=1.18 was considered positive.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria

  • Diagnosis of tumor type with the potential to have P-cadherin expression that is resistant to standard therapy or for which no standard therapy is available
  • Performance status of 0 or 1
  • Adequate bone marrow, kidney and liver function

Key Exclusion Criteria

  • Known CNS disease including, but not limited to, metastases
  • Current or history of seizure disorder
  • History of or active autoimmune disorders
  • Active bacterial, fungal or viral infection
  • Major surgery, anti-cancer therapy, or radiation therapy within 4 weeks of study treatment
  • Requirement for systemic immune suppressive medication
  • Grade 2 or greater peripheral neuropathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659631


Locations
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United States, New York
Memorial Sloan Kettering Cancer Center - Westchester
Harrison, New York, United States, 10604
Memorial Sloan Kettering Cancer Center- Clinical Trials Office
New York, New York, United States, 10017
Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion
New York, New York, United States, 10022
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
United States, Texas
The University of Texas - M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Hospital
Salt Lake City, Utah, United States, 84112
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] January 12, 2018
Statistical Analysis Plan  [PDF] July 17, 2018

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02659631    
Other Study ID Numbers: B7831001
First Posted: January 20, 2016    Key Record Dates
Results First Posted: May 6, 2020
Last Update Posted: May 6, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Keywords provided by Pfizer:
P-cadherin
PF-06671008
solid tumors
lung cancer
breast cancer
colorectal cancer
NSCLC
TNBC
CRC
neoplasms
Triple negative breast cancer
Non-small cell lung cancer
Additional relevant MeSH terms:
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Neoplasms