Description:
Open-label, multi-center, non-randomized, multiple dose, safety, tolerability,
pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06873600 administered
as a single agent and then in combination with endocrine therapy. The study contains two
parts, a Part 1 single agent dose escalation and combination endocrine therapy dose finding
component and a Part 2 dose expansion in combination with endocrine therapy.
Title
- Brief Title: A Safety, Pharmacokinetic, Pharmacodynamic and Anti-Tumor Study of PF-06873600 as a Single Agent and in Combination With Endocrine Therapy
- Official Title: PHASE 1/2A DOSE ESCALATION AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMICS AND ANTI-TUMOR ACTIVITY OF PF-06873600 AS A SINGLE AGENT AND IN COMBINATION WITH ENDOCRINE THERAPY
Clinical Trial IDs
- ORG STUDY ID:
C3661001
- NCT ID:
NCT03519178
Conditions
- HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
PF-06873600 | | Dose Escalation |
Endocrine Therapy 1 | | Dose Expansion Arm C |
Endocrine Therapy 2 | | Dose Expansion Arm E |
Purpose
Open-label, multi-center, non-randomized, multiple dose, safety, tolerability,
pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06873600 administered
as a single agent and then in combination with endocrine therapy. The study contains two
parts, a Part 1 single agent dose escalation and combination endocrine therapy dose finding
component and a Part 2 dose expansion in combination with endocrine therapy.
Detailed Description
This is a Phase 1/2a, open-label, multi-center, non-randomized, multiple dose, safety,
tolerability, pharmacokinetic, and pharmacodynamic study of PF-06873600 administered as a
single agent in sequential dose levels and then in combination with endocrine therapy. In
Part 1A and Part 1C, successive cohorts of patients will receive escalating doses of
PF-06873600 and then in dose finding (Part 1B) with PF-06873600 in combination with endocrine
therapy (ET). This study contains 2 parts, dose escalation with single agent (Part 1A and 1C)
and then dose finding with PF-06873600 in combination with endocrine therapy (Part 1B)
followed by dose expansion arms of PF-06873600 in combination with endocrine therapy (Part
2).
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation | Experimental | Single Agent Dose Escalation | |
Dose Finding Endocrine Therapy 1 Combination | Experimental | Part 1B PF-06873600 plus Endocrine Therapy 1 | - PF-06873600
- Endocrine Therapy 1
|
Dose Finding Endocrine Therapy 2 Combination | Experimental | Part 1B PF-06873600 plus Endocrine Therapy 2 | - PF-06873600
- Endocrine Therapy 2
|
Dose Expansion Arm A | Experimental | PF-06873600 as a Single Agent | |
Dose Expansion Arm B | Experimental | PF-06873600 as a Single Agent in Various Tumor Types | |
Dose Expansion Arm C | Experimental | PF-06873600 in Combination with Endocrine Therapy 1 | - PF-06873600
- Endocrine Therapy 1
|
Dose Expansion Arm D | Experimental | PF-06873600 in Combination with Endocrine Therapy 1 | - PF-06873600
- Endocrine Therapy 1
|
Dose Expansion Arm E | Experimental | PF-06873600 in Combination with Endocrine Therapy 2 | - PF-06873600
- Endocrine Therapy 2
|
Eligibility Criteria
Inclusion Criteria:
- Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor
Receptor 2 Negative (HER2-) breast cancer
• Prior combined CDK 4/6 inhibitor and endocrine therapy and 1 or 2 prior lines of
chemotherapy
- Have a diagnosis of metastatic triple negative breast cancer (TNBC)
• Up to 1-2 prior lines of chemotherapy
- Have a diagnosis of advanced platinum resistant epithelial ovarian cancer
(EOC)/fallopian tube cancer/primary peritoneal cancer (PPC)
• Up to 2-3 prior lines of therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- Measurable disease or non-measurable disease and refractory to or intolerant of
existing therapies (Part 1)
- Measurable disease as defined by RECIST 1.1 is required (Part 1B and Part 2 only)
Exclusion Criteria:
- Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases
- Other active malignancy within 3 years prior to randomization, except for adequately
treated basal cell or squamous cell skin cancer, or carcinoma in situ
- Major surgery or radiation within 4 weeks prior to study entry
- Last anti-cancer treatment within 2 weeks prior to study entry
- Participation in other studies involving investigational drug(s) within 4 weeks prior
to study entry
- Pregnant or breastfeeding female patients
- Active inflammatory gastrointestinal (GI) disease, known diverticular disease or
previous gastric resection or lap band surgery including impairment of gastro
intestinal function or GI disease
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of patients with dose limiting toxicities in the Dose Escalation portion |
Time Frame: | up to 28 days |
Safety Issue: | |
Description: | Adverse events |
Secondary Outcome Measures
Measure: | Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Single Dose: Plasma concentrations with and without food observed in patients enrolled in one of the single agent Dose Expansion Arms |
Time Frame: | 7 days prior to Cycle 1 (each cycle is 28 days) and in Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Single Dose: Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Single Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | Pharmacokinetic (PK) assessments for PF-06873600 |
Measure: | Tumor Response observed in patients in Dose Escalation and Dose Finding portion |
Time Frame: | baseline up to approximately 24 months |
Safety Issue: | |
Description: | |
Measure: | Duration of Response (DOR) in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | baseline up to approximately 24 months |
Safety Issue: | |
Description: | |
Measure: | Progression Free Survival (PFS) observed in patients in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | baseline up to approximately 24 months |
Safety Issue: | |
Description: | |
Measure: | Time to Progression (TTP) observed in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | baseline up to approximately 24 months |
Safety Issue: | |
Description: | |
Measure: | Overall Survival observed in patients enrolled in the Dose Expansion Arms |
Time Frame: | baseline up to approximately 24 months |
Safety Issue: | |
Description: | |
Measure: | Pharmacodynamic (PD) biomarkers (pRb and Ki67) in tumor tissue in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |
Time Frame: | Screening, Cycle 1 (each cycle is 28 days), Cycle 2 and 3 and at the study completion visit, up to approximately 24 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Pfizer |
Trial Keywords
- Hormone Receptor (HR) Positive Breast Cancer
- Estrogen receptor (ER) positive
- Progesterone receptor (PR) positive
- Cyclin-dependent kinase (CDK)
- Human epidermal growth factor receptor 2 (HER2) negative
- Advanced breast cancer
- Metastatic breast cancer (MBC)
- Triple negative breast cancer (TNBC)
- Epithelial ovarian cancer (EOC)
- Fallopian tube cancer
- Primary peritoneal cancer (PPC)
- CDK4/6 inhibitor
- Endocrine Therapy (ET)
- Measurable disease
- Luteinizing Hormone Releasing Hormone (LHRH) Agonist
- Goserelin
- Leuprolide acetate
Last Updated
August 19, 2021