A Study of PF-06873600 in People With Cancer
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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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03519178 |
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Recruitment Status :
Active, not recruiting
First Posted : May 8, 2018
Last Update Posted : December 26, 2023
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
- Study Details
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer | Drug: PF-06873600 Drug: Endocrine Therapy 1 Drug: Endocrine Therapy 2 | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 155 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 7, 2018 |
| Actual Primary Completion Date : | April 5, 2023 |
| Estimated Study Completion Date : | November 28, 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation
Single Agent Dose Escalation
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Drug: PF-06873600
PF-06873600 tablet for oral dosing |
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Experimental: Dose Finding Endocrine Therapy 1 Combination
Part 1B PF-06873600 plus Endocrine Therapy 1
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Drug: PF-06873600
PF-06873600 tablet for oral dosing Drug: Endocrine Therapy 1 Endocrine Therapy 1 |
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Experimental: Dose Finding Endocrine Therapy 2 Combination
Part 1B PF-06873600 plus Endocrine Therapy 2
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Drug: PF-06873600
PF-06873600 tablet for oral dosing Drug: Endocrine Therapy 2 Endocrine Therapy 2 |
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Experimental: Dose Expansion Arm A
PF-06873600 as a Single Agent
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Drug: PF-06873600
PF-06873600 tablet for oral dosing |
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Experimental: Dose Expansion Arm B
PF-06873600 as a Single Agent in Various Tumor Types
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Drug: PF-06873600
PF-06873600 tablet for oral dosing |
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Experimental: Dose Expansion Arm C
PF-06873600 in Combination with Endocrine Therapy 1
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Drug: PF-06873600
PF-06873600 tablet for oral dosing Drug: Endocrine Therapy 1 Endocrine Therapy 1 |
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Experimental: Dose Expansion Arm D
PF-06873600 in Combination with Endocrine Therapy 1
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Drug: PF-06873600
PF-06873600 tablet for oral dosing Drug: Endocrine Therapy 1 Endocrine Therapy 1 |
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Experimental: Dose Expansion Arm E
PF-06873600 in Combination with Endocrine Therapy 2
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Drug: PF-06873600
PF-06873600 tablet for oral dosing Drug: Endocrine Therapy 2 Endocrine Therapy 2 |
Primary Outcome Measures :
- 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
Secondary Outcome Measures :
- 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 ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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
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Have a diagnosis of metastatic triple negative breast cancer (TNBC)
• Up to 1-2 prior lines of chemotherapy
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03519178
Locations
Show 56 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT03519178 |
| Other Study ID Numbers: |
C3661001 |
| First Posted: | May 8, 2018 Key Record Dates |
| Last Update Posted: | December 26, 2023 |
| Last Verified: | December 2023 |
| Individual Participant Data (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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Pfizer:
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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 |
Additional relevant MeSH terms:
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Breast Neoplasms Ovarian Neoplasms Triple Negative Breast Neoplasms Fallopian Tube Neoplasms Breast Neoplasms, Male Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Endocrine Gland Neoplasms Ovarian Diseases |
Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female Urogenital Neoplasms Genital Diseases Endocrine System Diseases Gonadal Disorders Fallopian Tube Diseases |