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Trial record 1 of 1 for:    NCT02129205
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A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors

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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

Tracking Information
First Submitted Date  ICMJE April 30, 2014
First Posted Date  ICMJE May 2, 2014
Results First Submitted Date  ICMJE June 12, 2018
Results First Posted Date  ICMJE March 29, 2019
Last Update Posted Date March 29, 2019
Actual Study Start Date  ICMJE June 2014
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 30, 2014)
  • Number of participants with Dose-Limiting Toxicities (DLT) [Part 1] [ Time Frame: Day 1 up to Day 21 ]
    First cycle DLTs in order to determine maximum tolerated dose
  • Number of participants with objective response [Part 2] [ Time Frame: Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months ]
    Response rate as determined by RECIST v 1.1
Change History Complete list of historical versions of study NCT02129205 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2014)
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Scheduled timepoints from Day 1 up to Day 84 and then every 21 days thereafter for up to 24 months ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Scheduled timepoints from Day 1 up to Day 84 and then every 21 days thereafter for up to 24 months ]
  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [ Time Frame: Scheduled timepoints from Day 1 up to Day 84 and then every 21 days thereafter for up to 24 months ]
  • Systemic Clearance (CL) [ Time Frame: Scheduled timepoints from Day 1 up to Day 84 and then every 21 days thereafter for up to 24 months ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.
  • Incidence of anti-drug antibodies [ Time Frame: Day 1, 15, 21, and every 21 days thereafter up to 24 months ]
    Number of participants with the presence of anti-PF-06650808 antibodies
  • Number of participants with objective response, PFS and OS [Part 2] [ Time Frame: Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months ]
  • Volume of Distribution at Steady State (Vss) [ Time Frame: Scheduled timepoints from Day 1 up to Day 84 and then every 21 days thereafter for up to 24 months ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
  • Plasma Decay Half-Life (t1/2) [ Time Frame: Scheduled timepoints from Day 1 up to Day 84 and then every 21 days thereafter for up to 24 months ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors
Official Title  ICMJE A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06650808 IN PATIENTS WITH ADVANCED SOLID TUMORS
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neoplasms
  • Breast Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: PF-06650808
Interventions:
  • Drug: PF-06650808
  • Drug: PF-06650808
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 24, 2017)
40
Original Estimated Enrollment  ICMJE
 (submitted: April 30, 2014)
55
Actual Study Completion Date  ICMJE July 2017
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02129205
Other Study ID Numbers  ICMJE B7501001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP