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A Dose Escalation Study of PF‑06939999 in Participants With Advanced or Metastatic Solid Tumors.

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ClinicalTrials.gov Identifier: NCT03854227
Recruitment Status : Recruiting
First Posted : February 26, 2019
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

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 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
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 : July 27, 2022
Estimated Study Completion Date : July 27, 2022


Arm Intervention/treatment
Experimental: Dose Level 1
Participants will receive PF-06939999 at 0.5 mg once a day (QD) in 28 day cycles on a continuous basis
Drug: PF-06939999
0.5 mg QD orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 2
Participants will receive PF-06939999 at 0.5 mg BID in 28 day cycles on a continuous basis
Drug: PF-06939999
0.5 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 3
Participants will receive PF-06939999 at 1 mg twice a day (BID) in 28 day cycles on a continuous basis
Drug: PF-06939999
1 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 4
Participants will receive PF-06939999 at 2 mg BID in 28 day cycles on a continuous basis
Drug: PF-06939999
2 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 5
Participants will receive PF-06939999 at 4 mg BID in 28 day cycles on a continuous basis
Drug: PF-06939999
4 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 6
Participants will receive PF-06939999 at 8 mg BID in 28 day cycles on a continuous basis
Drug: PF-06939999
8 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 7
Participants will receive PF-06939999 at 16 mg BID in 28 day cycles on a continuous basis
Drug: PF-06939999
16 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 8
Participants will receive PF-06939999 at 30 mg BID in 28 day cycles on a continuous basis
Drug: PF-06939999
30 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor

Experimental: Dose Level 9
Participants will receive PF-06939999 at 60 mg BID in 28 day cycles on a continuous basis
Drug: PF-06939999
60 mg BID orally on a continuous basis
Other Name: PRMT5 inhibitor




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 approximately 2 years ]
    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 approximately 2 years ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing.


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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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 hours post dose; predose on Cycle 1 Days 2, 8 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. Objective Response Rate [ Time Frame: Baseline through up to 24 months ]
    Tumor response as assessed using RECIST 1.1

  15. Duration of response (DoR) [ Time Frame: Baseline through up to 24 months ]
    Duration of response as assessed using RECIST 1.1



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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:

  • Participants who are intolerant or resistant to standard treatment for selected solid tumors
  • 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
  • Known or suspected hypersensitivity to PF-06939999
  • Inability to consume or absorb study drug

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, Tennessee
Henry-Joyce Cancer Clinic Not yet recruiting
Nashville, Tennessee, United States, 37232
Vanderbilt-Ingram Cancer Center Not yet 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 Not yet recruiting
Annandale, Virginia, United States, 22003
Inova Schar Cancer Institute Infusion Pharmacy Not yet recruiting
Fairfax, Virginia, United States, 22031
Inova Schar Cancer Institute Not yet recruiting
Fairfax, Virginia, United States, 22031
United States, Washington
Seattle Cancer Care Alliance Not yet recruiting
Seattle, Washington, United States, 98109
University of Washington Medical Center Not yet recruiting
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03854227     History of Changes
Other Study ID Numbers: C3851001
First Posted: February 26, 2019    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2019
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