Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : November 1, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 15, 2019
First Posted Date  ICMJE February 26, 2019
Last Update Posted Date November 1, 2019
Actual Study Start Date  ICMJE March 14, 2019
Estimated Primary Completion Date July 27, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • 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)
  • 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
  • Number of participants with laboratory abnormalities [ Time Frame: Baseline through approximately 2 years ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03854227 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • 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).
  • 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).
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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).
  • 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).
  • 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)
  • 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)
  • 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)
  • 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)
  • Objective Response Rate [ Time Frame: Baseline through up to 24 months ]
    Tumor response as assessed using RECIST 1.1
  • Duration of response (DoR) [ Time Frame: Baseline through up to 24 months ]
    Duration of response as assessed using RECIST 1.1
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 A Dose Escalation Study of PF‑06939999 in Participants With Advanced or Metastatic Solid Tumors.
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Metastatic Solid Tumors
Intervention  ICMJE
  • Drug: PF-06939999
    0.5 mg QD orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    0.5 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    1 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    2 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    4 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    8 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    16 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    30 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
  • Drug: PF-06939999
    60 mg BID orally on a continuous basis
    Other Name: PRMT5 inhibitor
Study Arms  ICMJE
  • 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
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 2
    Participants will receive PF-06939999 at 0.5 mg BID in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 3
    Participants will receive PF-06939999 at 1 mg twice a day (BID) in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 4
    Participants will receive PF-06939999 at 2 mg BID in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 5
    Participants will receive PF-06939999 at 4 mg BID in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 6
    Participants will receive PF-06939999 at 8 mg BID in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 7
    Participants will receive PF-06939999 at 16 mg BID in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 8
    Participants will receive PF-06939999 at 30 mg BID in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
  • Experimental: Dose Level 9
    Participants will receive PF-06939999 at 60 mg BID in 28 day cycles on a continuous basis
    Intervention: Drug: PF-06939999
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: February 22, 2019)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 27, 2022
Estimated Primary Completion Date July 27, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03854227
Other Study ID Numbers  ICMJE C3851001
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 October 2019

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