A Study of PF-06873600 in People With Cancer

• ClinicalTrials.gov Identifier: NCT03519178
• Recruitment Status: Active, not recruiting
• First Posted: May 8, 2018
• Last Update Posted: December 26, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 22, 2018
• First Posted Date: May 8, 2018
• Last Update Posted Date: December 26, 2023
• Actual Study Start Date: March 7, 2018
• Actual Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2018)

• Number of patients with dose limiting toxicities in the Dose Escalation portion [ Time Frame: up to 28 days ]
• Safety and Tolerability as assessed by adverse event monitoring for patients enrolled in the Dose Escalation, Dose Finding and Dose Expansion Arms [ Time Frame: Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months ]
  Adverse events
• Safety and Tolerability as assessed through monitoring of hematology and blood chemistry laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms [ Time Frame: Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months ]
  safety laboratory abnormalities
• Safety and Tolerability as assessed through vital sign monitoring for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms [ Time Frame: Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months ]
  vital signs
• Safety and Tolerability as assessed by heart rate corrected QT interval for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms [ Time Frame: Day 1, 8 and 15 of Cycle 1 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months ]
  heart rate corrected QT interval
• Objective Response Rate (ORR) observed in patients in the Dose Expansion Arms [ Time Frame: baseline up to approximately 24 months ]
  Number of patients in each Arm. ORR (number of patients with a Partial Response (PR) + Complete Response (CR) relative to the number of evaluable patients
• Safety and Tolerability as assessed through monitoring of coagulation laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms [ Time Frame: Day 1 of Cycle 1 (each cycle is 28 days) and 2 and at completion, approximately 24 months ]
  safety laboratory abnormalities
• Safety and Tolerability as assessed through monitoring of urinalysis laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms [ Time Frame: Screening and at completion, approximately 24 months ]
  safety laboratory abnormalities

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 25, 2018)

• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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) ]
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• 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 ]
  Pharmacokinetic (PK) assessments for PF-06873600
• Tumor Response observed in patients in Dose Escalation and Dose Finding portion [ Time Frame: baseline up to approximately 24 months ]
• 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 ]
• 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 ]
• 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 ]
• Overall Survival observed in patients enrolled in the Dose Expansion Arms [ Time Frame: baseline up to approximately 24 months ]
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of PF-06873600 in People With Cancer
• 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

Brief Summary

The purpose of this clinical trial is to learn about the safety and effects of study medicine (PF-06873600) when taken alone or with hormone therapy by people with cancer.

People may be able to participate in this study if they have the following types of cancer: Hormone Receptor positive (HR+) breast cancer; Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer that is advanced or metastatic (spread to other parts of the body); triple negative breast cancer; epithelial ovarian cancer; fallopian tube cancer; or primary peritoneal cancer.

All participants in this study will receive the study medicine by mouth, 1 to 2 times a day at home. The dose of the study medicine may be changed during the study.

Some participants will also receive hormone therapy. The hormone therapy will be either letrozole by mouth once a day at home, or fulvestrant as a shot into the muscle. Fulvestrant will be given every two weeks at the study clinic for the first month, and then once a month after that.

Participants will take part in this study for at least 7 to 8 months, depending on how they respond to the therapy. During this time participants will visit the study clinic once a week.

• 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).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer

Intervention

• Drug: PF-06873600
  PF-06873600 tablet for oral dosing
• Drug: Endocrine Therapy 1
  Endocrine Therapy 1
• Drug: Endocrine Therapy 2
  Endocrine Therapy 2

Study Arms

• Experimental: Dose Escalation
  Single Agent Dose Escalation
  Intervention: Drug: PF-06873600
• Experimental: Dose Finding Endocrine Therapy 1 Combination
  Part 1B PF-06873600 plus Endocrine Therapy 1
  Interventions:

  • Drug: PF-06873600
  • Drug: Endocrine Therapy 1
• Experimental: Dose Finding Endocrine Therapy 2 Combination
  Part 1B PF-06873600 plus Endocrine Therapy 2
  Interventions:

  • Drug: PF-06873600
  • Drug: Endocrine Therapy 2
• Experimental: Dose Expansion Arm A
  PF-06873600 as a Single Agent
  Intervention: Drug: PF-06873600
• Experimental: Dose Expansion Arm B
  PF-06873600 as a Single Agent in Various Tumor Types
  Intervention: Drug: PF-06873600
• Experimental: Dose Expansion Arm C
  PF-06873600 in Combination with Endocrine Therapy 1
  Interventions:

  • Drug: PF-06873600
  • Drug: Endocrine Therapy 1
• Experimental: Dose Expansion Arm D
  PF-06873600 in Combination with Endocrine Therapy 1
  Interventions:

  • Drug: PF-06873600
  • Drug: Endocrine Therapy 1
• Experimental: Dose Expansion Arm E
  PF-06873600 in Combination with Endocrine Therapy 2
  Interventions:

  • Drug: PF-06873600
  • Drug: Endocrine Therapy 2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 9, 2022): 155
• Original Estimated Enrollment (submitted: April 25, 2018): 220
• Estimated Study Completion Date: November 28, 2024
• Actual Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Japan, Russian Federation, Ukraine, United States

Administrative Information

• NCT Number: NCT03519178
• Other Study ID Numbers: C3661001
• 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

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: December 2023