Clinical Trials /

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

NCT03854227

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Cervical Carcinoma
  • Endometrial Carcinoma
  • Esophageal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: C3851001
  • NCT ID: NCT03854227

Conditions

  • Advanced Solid Tumors
  • Metastatic Solid Tumors

Interventions

DrugSynonymsArms
PF-06939999PRMT5 inhibitorDose Level 1
PF-06939999PRMT5 inhibitorDose Level 2
PF-06939999PRMT5 inhibitorDose Level 3
PF-06939999PRMT5 inhibitorDose Level 4
PF-06939999PRMT5 inhibitorDose Level 5
PF-06939999PRMT5 inhibitorDose Level 6
PF-06939999PRMT5 inhibitorDose Level 7
PF-06939999PRMT5 inhibitorDose Level 8
PF-06939999PRMT5 inhibitorDose Level 9

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose Level 1ExperimentalParticipants will receive PF-06939999 at 0.5 mg once a day (QD) in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 2ExperimentalParticipants will receive PF-06939999 at 0.5 mg BID in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 3ExperimentalParticipants will receive PF-06939999 at 1 mg twice a day (BID) in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 4ExperimentalParticipants will receive PF-06939999 at 2 mg BID in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 5ExperimentalParticipants will receive PF-06939999 at 4 mg BID in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 6ExperimentalParticipants will receive PF-06939999 at 8 mg BID in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 7ExperimentalParticipants will receive PF-06939999 at 16 mg BID in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 8ExperimentalParticipants will receive PF-06939999 at 30 mg BID in 28 day cycles on a continuous basis
  • PF-06939999
Dose Level 9ExperimentalParticipants will receive PF-06939999 at 60 mg BID in 28 day cycles on a continuous basis
  • PF-06939999

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose limiting toxicities (DLTs)
Time Frame:Baseline through day 28
Safety Issue:
Description:DLTs will be evaluated during the first cycle. The number of DLTs will be used to determine the maximum tolerated dose (MTD)

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Single dose PK will be calculated including Maximum Observed Plasma Concentration (Cmax).
Measure: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
Safety Issue:
Description:Single dose PK will be calculated including Time to reach Maximum Observed Plasma Concentration (Tmax).
Measure: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
Safety Issue:
Description: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)
Measure: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
Safety Issue:
Description:Single dose PK will be calculated including, as data permit, terminal elimination half life (t1/2)
Measure: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
Safety Issue:
Description:Single dose PK will be calculated including, as data permit, Area Under the Curve from time 0 extrapolated to infinity (AUCinf)
Measure: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
Safety Issue:
Description:Single dose PK will be calculated including, as data permit, apparent oral plasma clearance (CL/F)
Measure: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
Safety Issue:
Description:Single dose PK will be calculated including, as data permit, apparent volume of distribution (Vz/F)
Measure: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
Safety Issue:
Description:Multiple dose PK will be calculated including Maximum Observed Steady State Plasma Concentration (Css,max).
Measure: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
Safety Issue:
Description:Multiple dose PK will be calculated including Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max).
Measure: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
Safety Issue:
Description:Multiple dose PK will be calculated including Area Under the Curve within one dose interval (AUCss,t)
Measure: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
Safety Issue:
Description:Multiple dose PK will be calculated including, as data permit, steady state apparent oral plasma clearance (CL/F)
Measure: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
Safety Issue:
Description:Multiple dose PK will be calculated including, as data permit, steady state apparent volume of distribution (Vss/F)
Measure: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
Safety Issue:
Description:Multiple dose PK will be calculated including, as data permit, accumulation ratio (Rac)
Measure:Objective Response Rate
Time Frame:Baseline through up to 24 months
Safety Issue:
Description:Tumor response as assessed using RECIST 1.1
Measure:Duration of response (DoR)
Time Frame:Baseline through up to 24 months
Safety Issue:
Description:Duration of response as assessed using RECIST 1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Last Updated