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A Dose Escalation Study of PF-06650808 in Patients With 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: NCT02129205
Recruitment Status : Terminated (The study was terminated due to a change in sponsor prioritization.)
First Posted : May 2, 2014
Results First Posted : March 29, 2019
Last Update Posted : March 29, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
To assess the safety and tolerability at increasing dose levels of PF-06650808 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Condition or disease Intervention/treatment Phase
Neoplasms Breast Cancer Drug: PF-06650808 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06650808 IN PATIENTS WITH ADVANCED SOLID TUMORS
Actual Study Start Date : June 2014
Actual Primary Completion Date : July 2017
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-06650808 Drug: PF-06650808
Dose Escalation Phase [Part 1] - PF-06650808 will be administered at doses starting at 0.2 mg/kg. Increases in dose will continue until MTD is determined.

Drug: PF-06650808
Dose Expansion Phase [Part 2] - Patients will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.




Primary Outcome Measures :
  1. Number of Participants With Dose-limiting Toxicities (DLT) (Part 1) [ Time Frame: Day 1 up to Day 21 ]
    Severity of AEs (adverse events ) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the purpose of dose escalation, any of the following AEs which were not considered related to disease progression occurring in the first cycle of treatment (21 days) were classified as DLTs: 1) Hematologic: Grade 4 neutropenia lasting >7 days; Febrile neutropenia; Grade>=3 neutropenia with infection; Any grade thrombocytopenia associated with clinically significant or life threatening bleeding; Grade 4 thrombocytopenia >=72 hours or platelets<=10,000/mm3 regardless of duration. 2) Non hematologic: Grade>=3 toxicities except those that had not been maximally treated; Delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression. 3) clinically important or persistent toxicities may have been considered a DLT following review by the Sponsor and the investigators.

  2. Percentage of Participants With Objective Response (Part 1 and Part 2) [ Time Frame: Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 3 years ]
    Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant achieved complete response (CR) if both target and non-target lesions achieved CR, no new lesions; achieved partial response (PR) if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits. The overall objective response was defined as confirmed CR and PR.


Secondary Outcome Measures :
  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 1 and Part 2) [ Time Frame: 3 years ]
    AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  2. Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Hematology) (Part 1 and Part 2) [ Time Frame: 3 years ]
    Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. The participants who experienced laboratory test abnormalities were determined by investigators.

  3. Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Chemistries) (Part 1 and Part 2) [ Time Frame: 3 years ]
    Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus, bicarbonate or carbon dioxide, total protein and lactate dehydrogenase. The participants who experienced laboratory test abnormalities were determined by investigators.

  4. Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Urinalysis) (Part 1 and Part 2) [ Time Frame: 3 years ]
    Urinalysis included urine protein. Microscopic analyses were performed if dipstick was abnormal. The participants who experienced laboratory test abnormalities were determined by investigators.

  5. Number of Participants With Vital Signs Meeting Categorical Summarization Criteria (Part 1 and Part 2) [ Time Frame: 3 years ]
    Vital Signs tests included systolic and diastolic blood pressure (BP) and pulse rate of seated supine and standing . Vital signs categorical summarization criteria were 1), supine and standing BP: systolic (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from baseline, diastolic <50 mm Hg; 2), supine and standing pulse rate <40 or greater than (>) 120 beats per minute (bpm).

  6. Maximum Observed Serum Concentration (Cmax) (Part 1 and Part 2) [ Time Frame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 ]
    Maximum observed serum concentration (Cmax) of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were observed directly from data. PF-06650808 is comprised of an antibody (PF-06460005) and a cytotoxic agent (PF-06380101).

  7. Time to Reach Maximum Observed Serum Concentration (Tmax) (Part 1 and Part 2) [ Time Frame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 ]
    Tmax of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were observed directly from data as time of first occurrence.

  8. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) (Part 1 and Part 2) [ Time Frame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 ]
    Tau refers to the dosing interval, and it equals to 504 hours (3 weeks) of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were determined using linear/log trapezoidal method.

  9. Clearance (CL) (Part 1 and Part 2) [ Time Frame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL was calculated as dose/AUCinf, where AUCinf was the area under the serum concentration-time profile from time 0 extrapolated to infinite time. CL was only for PF-06650808 (ADC) and Cycle 1.

  10. Volume of Distribution at Steady State (Vss) (Part 1 and Part 2) [ Time Frame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 ]
    Vss was calculated as dose/(AUCinf × kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Vss was only for PF-06650808 (ADC) and Cycle 1.

  11. Terminal Elimination Half-Life (t1/2) (Part 1 and Part 2) [ Time Frame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 ]
    Terminal elimination half-life was defined as the time measured for the serum concentration to decrease by one half, and calculated as loge(2)/kel.

  12. Number of Participants With the Presence of Anti-PF-06650808 Antibodies (Part 1 and Part 2) [ Time Frame: 3 years ]
    Assays to assess for anti drug (anti PF-06650808) antibodies (ADA) were performed. Positive ADA: titer>=1.88.

  13. Progression Free Survival and Overall Survival (Part 2) [ Time Frame: 3 years ]
    Progression Free Survival was defined as the time from Cycle 1 Day 1 (C1D1) to first documentation of disease progression or to death due to any cause, whichever occurs first. Overall survival was defined as the time from initial dose until death from any cause, and is measured in the intent to treat population.



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

Inclusion Criteria:

  • Diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available
  • Previously treated metastatic triple negative breast cancer that expresses Notch3 with at least one measurable lesion
  • Adequate bone marrow, renal and liver function

Exclusion Criteria:

  • Major surgery, radiation therapy or systemic anti-cancer therapy within 4 weeks of starting study treatment
  • Patients with known symptomatic brain metastases requiring steroids
  • Prior treatment with a compound of the same mechanism

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): NCT02129205


Locations
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United States, California
Ronald Reagan UCLA Medical Center, Drug Information Center
Los Angeles, California, United States, 90095
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States, 90095
UCLA Hematology/Oncology
Los Angeles, California, United States, 90095
Westwood Bowyer Clinic
Los Angeles, California, United States, 90095
Santa Monica - UCLA Medical Center & Orthopaedic Hospital
Santa Monica, California, United States, 90404
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, United States, 90404
United States, Ohio
The Ohio State University James Cancer Hospital
Columbus, Ohio, United States, 43210
The OSU Investigational Drug Services
Columbus, Ohio, United States, 43210
The OSU Stephanie Spielman Comprehensive Breast Center
Columbus, Ohio, United States, 43212
The Ohio State University Martha Morehouse Medical Plaza
Columbus, Ohio, United States, 43221
United States, Texas
South Texas Accelerated Research Therapeutics, LLC (START)
San Antonio, Texas, United States, 78229
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] May 7, 2014
Statistical Analysis Plan  [PDF] November 17, 2014


Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02129205     History of Changes
Other Study ID Numbers: B7501001
First Posted: May 2, 2014    Key Record Dates
Results First Posted: March 29, 2019
Last Update Posted: March 29, 2019
Last Verified: December 2018
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:
solid tumors
triple negative breast cancer
PF-06650808
Phase 1

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases