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Trial record 1 of 1 for:    c2321001
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PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

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ClinicalTrials.gov Identifier: NCT03460977
Recruitment Status : Recruiting
First Posted : March 9, 2018
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 12, 2018
First Posted Date  ICMJE March 9, 2018
Last Update Posted Date June 30, 2020
Actual Study Start Date  ICMJE April 17, 2018
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2018)
  • Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) [ Time Frame: Baseline up to 90 days ]
    First cycle DLTs will be utilized to determine the MTD and future dose escalations or de-escalations. A DLT is any of the predefined set of unacceptable adverse events observed and at least possibly related to investigational agents.
  • Overall safety profile including adverse events [ Time Frame: Baseline up to approximately 2 years ]
    Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any lab abnormalities. Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version [4.03]), timing, seriousness, and relationship to study therapy.
  • Preliminary efficacy determination as evaluated by disease specific response criteria [ Time Frame: Through study completion, approximately 2 years past last patient first visit. ]
    Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Working Group 3 (PWG3) for Castration Resistant Prostate Cancer (CRPC)
  • Overall safety profile including laboratory abnormalities [ Time Frame: Baseline up to approximately 2 years ]
    Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version [4.03]), and timing.
  • Overall safety profile including vital signs [ Time Frame: Baseline up to approximately 2 years ]
    Vital sign changes from baseline including blood pressure, heart rate, ECG changes.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2018)
  • Evaluate time to event anti-tumor activity of PF-06821497 including progression-free survival (PFS), and metastatic free survival (MFS) [ Time Frame: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years. ]
    Time to event endpoints based on Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Working Group 3 (PWG3) for Castration Resistant Prostate Cancer (CRPC)
  • Evaluate overall survival [ Time Frame: Baseline up to approximately 2 years ]
    Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
  • Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
    Single dose and multiple dose PK will be calculated as data permits including Maximum Observed Plasma Concentration (Cmax).
  • Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
    Single dose and multiple dose PK will be calculated as data permits including Time to Reach Maximum Observed Plasma Concentration (Tmax).
  • Pharmacokinetic Parameters: Area Under the Curve (AUC) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
    Single dose and multiple dose PK will be calculated as data permits including Area Under the Cuvce (AUC).
  • Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
    Single dose and multiple dose PK will be calculated as data permits including Apparent Oral Clearance (CL/F). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
    Single dose and multiple dose PK will be calculated as data permits including Apparent Volume of Distribution (Vz/F). 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
    Singe dose and multiple dose PK will be calculated as data permits including Plasma Decay Half-Life (t1/2). Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
Official Title  ICMJE A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF-06821497 IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)
Brief Summary A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 In The Treatment Of Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).
Detailed Description

This is an open label, multi center, Phase 1 dose escalation study of PF 06821497 administered orally as a single agent BID to patients with SCLC, CRPC, DLBCL and FL (Part 1A). For Part 1B (dose escalation monotherapy), PF 06821497 will be administered as monotherapy in patients with FL. For Part 2A (dose escalation combination therapy), PF 06821497 will be administered in combination with SOC in patients with SCLC and CRPC. For Part 2B (dose expansion), PF 06821497 will be administered in combination with SOC in patients with SCLC and CRPC, and as monotherapy in patients with FL.

Part 1A (escalation monotherapy) will assess PF 06821497 administered as a single agent twice daily in a continuous regimen to patients with advanced tumors (SCLC CRPC, DLBCL and FL). A modified toxicity probability interval (mTPI) dose finding design will be applied in 2 4 patient cohorts. The starting dose of PF 06821497 will be 75 mg BID (DL1). Once the safety and adequate target modulation has been established Parts 1B and 2A of the trial will be initiated. Additional dose levels may be investigated, if adequate target inhibition has not been achieved at DL3.

Part 1B [escalation recommended Phase 2 dose (RP2D) finding - monotherapy] will determine the maximum tolerated dose (MTD) of monotherapy in FL (MTD1).

Part 2A (escalation RP2D finding -combination) will determine the MTD of the combination with SOC in patients with SCLC (cisplatin or carboplatin with etoposide, MTD2, MTD3) and CRPC (MTD4). Part 2B (dose expansion) will assess the efficacy of PF 06821497 at the RP2D identified from the Part 2A, in combination with SOC in patients with SCLC (n=16 to 30 for the 2 combination regimens), and CRPC (n=8 to 20) in addition to as a single agent twice daily in patients with FL (n=8 to 20).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Small Cell Lung Cancer (SCLC)
  • Follicular Lymphoma (FL)
  • Castration Resistant Prostate Cancer (CRPC)
  • Diffuse Large B-Cell Lymphoma (DLBCL)
Intervention  ICMJE Drug: PF-06821497
Oral continuous (Part 1)
Study Arms  ICMJE
  • Experimental: DL 1
    PF-06821497 75 mg BID
    Intervention: Drug: PF-06821497
  • Experimental: DL 2
    PF-06821497 150 mg BID
    Intervention: Drug: PF-06821497
  • Experimental: DL 3
    PF-06821497 250 mg BID
    Intervention: Drug: PF-06821497
  • Experimental: DL 4
    PF-06821497 375 mg BID
    Intervention: Drug: PF-06821497
  • Experimental: DL 5
    PF-06821497 500 mg BID
    Intervention: Drug: PF-06821497
  • Experimental: DL 6
    PF-06821497 625 mg BID
    Intervention: Drug: PF-06821497
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 2, 2018)
172
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2023
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:

Part 1A:

-Histologically / cytologically confirmed advanced/unresectable or metastatic SCLC, CRPC, DLBCL and FL that is refractory to or intolerable of standard treatment, or for which no curative treatment is available. Note for FL (Parts 1A and 1B) during the dose finding phase of study, follicular lymphoma patients must have exhausted all standard of care therapies.

Part 1B:

Histologically confirmed FL patients that have exhausted all curative therapies and have relapsed or refractory disease.

Part 2:

  • Histologically or cytologically confirmed treatment naïve extensive disease SCLC patients;
  • Histologically confirmed FL patients that are intolerant of or resistant to standard therapy or for which no curative therapy is available and have relapsed or refractory disease (Part 2B).
  • Histological / cytological diagnosis of castration resistant prostate cancer. Received either abiraterone and/or enzalutamide treatment and has evidence of prostate cancer progression (per PWG3):

    • SCLC patients entering the study in the expansion cohort with at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
    • FL patients entering the study in the expansion cohort with at least one measurable lesion as defined by Response Evaluation Criteria in Lymphoma (RECIL) criteria.
    • Females and/or male patients age 18 years.
    • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
    • Adequate Bone Marrow Function
    • Adequate Renal Function
    • Adequate Liver Function
    • Serum pregnancy test (for females of childbearing potential) negative at screening, and negative serum or urine pregnancy test at baseline prior to treatment administration.

Exclusion Criteria:

  • Known symptomatic brain metastases requiring steroids or CNS involvement in FL. Previously diagnosed brain metastases are eligible if they have been treated and recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Physiologic replacement doses of corticosteroids are permissible.
  • At least 3 weeks since last major surgery (a lesser period is acceptable if decided to be in the best interest of the SCLC patient).
  • Treatment with more than 2gm acetaminophen per day within 14 days of study entry and on study if required.
  • Chronic liver diseases.
  • History of alcohol abuse or binge drinking in the last 6 months prior to screening.
  • Radiation therapy within 4 weeks prior to study entry. Note, patients who have received radiotherapy must have recovered from any reversible side effects, such as nausea and vomiting.
  • Systemic anti cancer therapy - approved or investigational - within 4 weeks or 5 half-lives, whichever is shorter, prior to study entry, including antibody based agents. Prostate cancer cohorts 2A and 2B must have not received more than 1 previous regimen of systemic chemotherapy in mCPRC setting. SCLC cohorts must be chemotherapy naive for SCLC however may have received one cycle of chemotherapy after discussion with the sponsor.
  • Last anti hormonal therapy within 2 weeks prior to C1D1.
  • Prior stem cell transplant, autologous or allogenic, within 100 days prior to study enrollment or patients who experienced graft veses host disease or who require systemic immune suppressive therapy.
  • Prior irradiation to >25% of the bone marrow.
  • Active and clinically significant bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
  • Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; ongoing cardiac dysrhythmias of NCI CTCAE Grade 2, atrial fibrillation of any grade, or QTcF interval >480 msec at screening.
  • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
  • Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC) or platinum compound.
  • Other acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
  • Pregnant female patients; breastfeeding female patients; fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 28days after the last dose of investigational product.
  • Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
  • Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.
  • Current use or anticipated need for drugs that are known strong CYP3A4/5 inducers, including their administration within 10 days or 5 half lives of the CYP3A4/5 inducer, whichever is longer prior to the first dose of investigational product.
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: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Italy,   Russian Federation,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03460977
Other Study ID Numbers  ICMJE C2321001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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 June 2020

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