PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
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| ClinicalTrials.gov Identifier: NCT03460977 |
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Recruitment Status :
Recruiting
First Posted : March 9, 2018
Last Update Posted : August 5, 2022
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Small Cell Lung Cancer (SCLC) Follicular Lymphoma (FL) Castration Resistant Prostate Cancer (CRPC) | Drug: PF-06821497 | Phase 1 |
This is an open label, multi center, Phase 1 dose escalation and dose expansion study of PF-06821497 administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. Part 1A will evaluate safety and target modulation of PF-06821497 monotherapy in patients with SCLC, FL and CRPC. PF-06821497 will be administered as monotherapy in patients with FL in Part 1B dose escalation and to patients with CRPC in Part 1C dose escalation. For Part 2A (dose escalation combination therapy), PF-06821497 will be administered in combination with SOC in patients with CRPC and SCLC. For Part 2B (dose expansion), patients with mCRPC will be randomized (1:1 ratio) to receive either SOC or PF-06821497 in combination with SOC. Once safety and adequate target modulation has been established in Part 1A, Parts 1B and 2A of the trial will be initiated. Part 1C (monotherapy dose escalation) will determine the MTD of single agent PF-06821497 in patients with mCRPC. Part 2A (escalation RP2D finding for combination) will determine the MTD of the combination with SOC in patients with CRPC. Part 2B (dose expansion) will assess the efficacy of PF-06821497 at the RP2D in combination with SOC in patients with mCRPC in comparison to SOC alone.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 185 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | April 17, 2018 |
| Estimated Primary Completion Date : | July 20, 2025 |
| Estimated Study Completion Date : | July 20, 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation (Part 1A)
Participants with SCLC, CRPC and FL will receive PF-06821497 at escalating dose levels
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Drug: PF-06821497
Oral continuous |
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Experimental: Dose Escalation (Part 1B)
Participants with FL will receive PF-06821497 at escalating dose levels
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Drug: PF-06821497
Oral continuous |
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Experimental: Dose Escalation (Part 1C)
Participants with CRPC will receive PF-06821497 at escalating dose levels.
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Drug: PF-06821497
Oral continuous |
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Experimental: Dose Escalation (Part 2A)
Participants with CRPC and SCLC will receive PF-06821497 at escalating dose levels in combination with SOC.
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Drug: PF-06821497
Oral continuous |
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Experimental: Dose Expansion (Part 2B)
Participants with CRPC will receive PF-06821497 in combination with SOC or SOC alone.
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Drug: PF-06821497
Oral continuous |
Primary Outcome Measures :
- 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
- Overall safety profile including adverse events [ Time Frame: Baseline up to approximately 2 years ]Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version [4.03])
- 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). Progression-free survival in Part 2B in patients with 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.
Secondary Outcome Measures :
- Evaluate time to event anti-tumor activity of PF-06821497 including progression-free survival (PFS), PSA50, Duration of Response (DoR), Time to first skeletal related event and Time to symptomatic skeletal related event, depending on tumor type. [ 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.
- Evaluate the impact of PF-06821497 on patient reported outcomes. [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 6 Day 1, Cycle 10 Day 1, Cycle 14 Day 1, Cycle 18 Day 1, Cycle 22 Day 1, Cycle 26 Day 1, Cycle 30 Day 1 and at End of Treatment visit. ]Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.
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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:
Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:
Part 1A (closed to enrollment):
Advanced/unresectable or metastatic SCLC, CRPC 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 (closed to enrollment):
FL; patients should have exhausted all curative therapies and have relapsed or refractory disease.
Part 1C:
Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PWG3)
Part 2A:
- Treatment naïve extensive disease SCLC patients;
- Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PWG3)
Part 2B:
Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, and have evidence of prostate cancer progression (per PWG3) Patients must have radiographic evidence of disease
Other inclusion criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
- Adequate organ function
Key Exclusion Criteria:
- Prior Chemotherapy: Part 1C (CRPC): no more than 2 previous regimens of chemotherapy
Part 2A:
CRPC: no more than 1 previous regimen of systemic chemotherapy SCLC: must be chemotherapy naive for SCLC (may have received one cycle of chemotherapy after discussion with the sponsor) Part 2B (CRPC): no more than 1 previous regimen of chemotherapy i
- Prior irradiation to >25% of the bone marrow.
- 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.
- 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 inducers or 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.
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): NCT03460977
Contacts
| Contact: Pfizer CT.gov Call Center | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Locations
Show 58 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT03460977 |
| Other Study ID Numbers: |
C2321001 |
| First Posted: | March 9, 2018 Key Record Dates |
| Last Update Posted: | August 5, 2022 |
| Last Verified: | August 2022 |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Pfizer:
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efficacy safety pharmacokinetics pharmacodynamics dose escalation dose expansion open-label EZH2 enhancer of zeste homolog 2 |
castrate resistant prostate cancer CRPC small cell lung cancer SCLC follicular lymphoma FL relapsed refractory |
Additional relevant MeSH terms:
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Lymphoma Lung Neoplasms Prostatic Neoplasms Lymphoma, Follicular Small Cell Lung Carcinoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Genital Neoplasms, Male Urogenital Neoplasms Prostatic Diseases Lymphoma, Non-Hodgkin Carcinoma, Bronchogenic Bronchial Neoplasms |