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A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03854227
Recruitment Status : Recruiting
First Posted : February 26, 2019
Last Update Posted : December 23, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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Brief Summary:
This is a Phase 1, open label, multi center, dose escalation and expansion, safety, tolerability, PK, and pharmacodynamics study of PF 06939999 in previously treated patients with advanced or metastatic cancer.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Metastatic Solid Tumors Drug: PF-06939999 dose escalation Drug: PF-06939999 monotherapy Drug: PF-06939999 in combination with docetaxel Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06939999 (PRMT5 INHIBITOR) IN PARTICIPANTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER, HEAD AND NECK SQUAMOUS CELL CARCINOMA, ESOPHAGEAL CANCER, ENDOMETRIAL CANCER, CERVICAL CANCER AND BLADDER CANCER
Actual Study Start Date : March 14, 2019
Estimated Primary Completion Date : May 27, 2022
Estimated Study Completion Date : November 26, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation
Participants will receive PF-06939999 orally at escalating doses in 28 day cycles on a continuous basis
 Drug: PF-06939999 dose escalation
PF-06939999 orally at escalating doses on a continuous basis
Other Name: PRMT5 inhibitor
Experimental: Non small cell lung cancer monotherapy
Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis
 Drug: PF-06939999 monotherapy
PF-06939999 at the recommended Phase 2 dose orally on a continuous basis
Other Name: PRMT5 inhibitor
Experimental: Urothelial carcinoma
Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis
 Drug: PF-06939999 monotherapy
PF-06939999 at the recommended Phase 2 dose orally on a continuous basis
Other Name: PRMT5 inhibitor
Experimental: Head and neck squamous cell carcinoma
Participants will receive PF-06939999 at the recommended Phase 2 dose in 28 day cycles on a continuous basis
 Drug: PF-06939999 monotherapy
PF-06939999 at the recommended Phase 2 dose orally on a continuous basis
Other Name: PRMT5 inhibitor
Experimental: Non small cell lung cancer PF-06939999 plus docetaxel
Participants will receive PF-06939999 on a continuous basis in combination with docetaxel
 Drug: PF-06939999 in combination with docetaxel
PF-06939999 orally on a continuous basis in combination with docetaxel
Other Name: PRMT5 inhibitor
Experimental: Non small cell lung cancer dose finding
Participants will receive PF-06939999 on a continuous basis at escalating doses in combination with docetaxel
 Drug: PF-06939999 in combination with docetaxel
PF-06939999 orally on a continuous basis in combination with docetaxel
Other Name: PRMT5 inhibitor


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Baseline through day 28 ]
    DLTs will be evaluated during the first cycle. The number of DLTs will be used to determine the maximum tolerated dose (MTD)

  2. Number of participants with treatment emergent adverse events (AEs) [ Time Frame: Baseline through up to 2 years or until disease progression ]
    Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy

  3. Number of participants with laboratory abnormalities [ Time Frame: Baseline through up to 2 years or until disease progression ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing.

  4. Objective Response Rate [ Time Frame: Baseline through up to 2 years or until disease progression ]
    Best Overall Response by RECIST 1.1


Secondary Outcome Measures :
  1. Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Single dose PK will be calculated including Maximum Observed Plasma Concentration (Cmax).

  2. Pharmacokinetic Parameters: Time to reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Single dose PK will be calculated including Time to reach Maximum Observed Plasma Concentration (Tmax).

  3. Pharmacokinetic Parameters: Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Single dose PK will be calculated including Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast)

  4. Pharmacokinetic Parameters: Terminal elimination half life (t1/2) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Single dose PK will be calculated including, as data permit, terminal elimination half life (t1/2)

  5. Pharmacokinetic Parameters: AUC from time 0 extrapolated to infinity (AUCinf) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Single dose PK will be calculated including, as data permit, Area Under the Curve from time 0 extrapolated to infinity (AUCinf)

  6. Pharmacokinetic Parameters: Apparent oral plasma clearance (CL/F) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Single dose PK will be calculated including, as data permit, apparent oral plasma clearance (CL/F)

  7. Pharmacokinetic Parameters: Apparent volume of distribution (Vz/F) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Single dose PK will be calculated including, as data permit, apparent volume of distribution (Vz/F)

  8. Pharmacokinetic Parameters: Maximum Observed Steady State Plasma Concentration (Css,max) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Multiple dose PK will be calculated including Maximum Observed Steady State Plasma Concentration (Css,max).

  9. Pharmacokinetic Parameters: Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Multiple dose PK will be calculated including Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max).

  10. Pharmacokinetic Parameters: Area Under the Curve within one dose interval (AUCss,t) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Multiple dose PK will be calculated including Area Under the Curve within one dose interval (AUCss,t)

  11. Pharmacokinetic Parameters: Steady state apparent oral plasma clearance (CL/F) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8. 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Multiple dose PK will be calculated including, as data permit, steady state apparent oral plasma clearance (CL/F)

  12. Pharmacokinetic Parameters: Steady state apparent volume of distribution (Vss/F) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Multiple dose PK will be calculated including, as data permit, steady state apparent volume of distribution (Vss/F)

  13. Pharmacokinetic Parameters: Accumulation ratio (Rac) [ Time Frame: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 ]
    Multiple dose PK will be calculated including, as data permit, accumulation ratio (Rac)

  14. Duration of response (DOR) [ Time Frame: Baseline through up to 2 years or until disease progression ]
    DOR as assessed using RECIST 1.1

  15. Progression free survival (PFS) [ Time Frame: Baseline through up to 2 years or until disease progression ]
    PFS as assessed using RECIST 1.1.

  16. Time to progression (TTP) [ Time Frame: Baseline through up to 2 years or until disease progression ]
    TTP as assessed using RECIST 1.1.

  17. Overall Survival (OS) [ Time Frame: Baseline through up to 2 years ]
    Proportion of participants alive at 6 months, 1 year and 2 years.


Eligibility Criteria
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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:

  • Histologically or cytologically confirmed locally advanced or metastatic NSCLC, urothelial carcinoma or HNSCC
  • Progressed after at least 1 line of treatment and no more than 3 lines of treatment
  • At least one measurable lesion as defined by RECIST version 1.1
  • ECOG Performance Status 0 or 1
  • Adequate Bone Marrow Function
  • Adequate Renal Function
  • Adequate Liver Function
  • Resolved acute effects of any prior therapy

Exclusion Criteria:

  • Known active uncontrolled or symptomatic CNS metastases.
  • Major surgery, radiation therapy, systemic anti-cancer therapy or investigational drug(s) within 4 weeks prior to study entry.
  • Active, uncontrolled infection, including COVID-19
  • Known or suspected hypersensitivity to PF-06939999
  • Inability to consume or absorb study drug
Contacts and Locations
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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): NCT03854227


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Arizona
Scottsdale Healthcare Hospitals d/b/a HonorHealth Recruiting
Scottsdale, Arizona, United States, 85258
Virginia G. Piper Cancer Pharmacy Recruiting
Scottsdale, Arizona, United States, 85258
United States, Florida
University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
United States, South Carolina
Prisma-Health Institute for Translational Oncology Research Not yet recruiting
Greenville, South Carolina, United States, 29605
United States, Tennessee
Henry-Joyce Cancer Clinic Recruiting
Nashville, Tennessee, United States, 37232
Oncology IDS Pharmacy Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
The University of Texas Recruiting
Houston, Texas, United States, 77030
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
United States, Virginia
Inova Schar Cancer Institute Active, not recruiting
Annandale, Virginia, United States, 22003
Inova Schar Cancer Institute Infusion Pharmacy Active, not recruiting
Fairfax, Virginia, United States, 22031
Inova Schar Cancer Institute Active, not recruiting
Fairfax, Virginia, United States, 22031
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03854227    
Other Study ID Numbers: C3851001
First Posted: February 26, 2019    Key Record Dates
Last Update Posted: December 23, 2020
Last Verified: December 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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
 Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action