A Study of PF-06873600 in People With Cancer

Phase 2TerminatedNCT03519178

Pfizer155 enrolled

Overview

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 for the first 2 cycles and every cycle thereafter.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (54)

University of Alabama at Birmingham

Birmingham, Alabama, United States

University Of Alabama at Birmingham

Birmingham, Alabama, United States

HonorHealth

Scottsdale, Arizona, United States

Virginia G. Piper Cancer Center Pharmacy

Scottsdale, Arizona, United States

Highlands Oncology Group

Fayetteville, Arkansas, United States

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs) - Part 1

DLT was defined as any of the following adverse events (AEs) occurring in the first cycle of treatment (28 days) which were attributable to one, the other, or both agents in the combination: Hematologic - grade(G) 4 neutropenia lasting \>7 days; Febrile neutropenia defined as an absolute neutrophil count (ANC) \<1.0 \* 10\^9/L with a single temperature of \>38.3°C, or a sustained temperature of ≥38°C, for more than 1 hour; G≥3 neutropenia with associated infection; G3 thrombocytopenia with clinically significant bleeding as indicated by ≥ G2 bleeding; G4 thrombocytopenia. Nonhematologic: Confirmed case of Drug Induced Liver Injury (DILI) (Hy's Law); G≥3 AEs that were clinically significant.

Time frame: Cycle 1 (within 28 days after the first dose of study intervention)

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) - Part 1 + Part 2

An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Treatment Related AEs were treatment emergent AEs with cause categorized by the investigator as related to study treatment.