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A Safety, Pharmacokinetic, Pharmacodynamic and Anti-Tumor Study of PF-06873600 as a Single Agent and in Combination With Endocrine Therapy

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ClinicalTrials.gov Identifier: NCT03519178
Recruitment Status : Recruiting
First Posted : May 8, 2018
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
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 as both a single agent and in combination with endocrine therapy.

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

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, 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 then dose finding with PF-06873600 in combination with endocrine therapy (Part 1B) followed by dose expansion arms as a single agent and PF-06873600 in combination with endocrine therapy (Part 2).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Single Group 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
Estimated Primary Completion Date : December 12, 2021
Estimated Study Completion Date : December 12, 2021


Arm Intervention/treatment
Experimental: Dose Escalation
Single Agent Dose Escalation
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Experimental: Dose Finding Endocrine Therapy 1 Combination
Part 1B PF-06873600 plus Endocrine Therapy 1
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Drug: Endocrine Therapy 1
Endocrine Therapy 1

Experimental: Dose Finding Endocrine Therapy 2 Combination
Part 1B PF-06873600 plus Endocrine Therapy 2
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Drug: Endocrine Therapy 2
Endocrine Therapy 2

Experimental: Dose Expansion Arm A
PF-06873600 as a Single Agent
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Experimental: Dose Expansion Arm B
PF-06873600 as a Single Agent in Various Tumor Types
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Experimental: Dose Expansion Arm C
PF-06873600 in Combination with Endocrine Therapy 1
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Drug: Endocrine Therapy 1
Endocrine Therapy 1

Experimental: Dose Expansion Arm D
PF-06873600 in Combination with Endocrine Therapy 1
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Drug: Endocrine Therapy 1
Endocrine Therapy 1

Experimental: Dose Expansion Arm E
PF-06873600 in Combination with Endocrine Therapy 2
Drug: PF-06873600
PF-06873600 tablet for oral dosing

Drug: Endocrine Therapy 2
Endocrine Therapy 2




Primary Outcome Measures :
  1. Number of patients with dose limiting toxicities in the Dose Escalation portion [ Time Frame: up to 28 days ]
  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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 :
  1. 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

  2. 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) ]
  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Tumor Response observed in patients in Dose Escalation and Dose Finding portion [ Time Frame: baseline up to approximately 24 months ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. Overall Survival observed in patients enrolled in the Dose Expansion Arms [ Time Frame: baseline up to approximately 24 months ]
  22. 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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 2)

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


Contacts
Layout table for location contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, California
Ronald Reagan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
UCLA Hematology Oncology Recruiting
Los Angeles, California, United States, 90095
UCSF Medical Center Not yet recruiting
San Francisco, California, United States, 94115
University of California -San Francisco Not yet recruiting
San Francisco, California, United States, 94115
UCLA Hematology/Oncology - Santa Monica Recruiting
Santa Monica, California, United States, 90404
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
The Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Investigational Pharmacy Services Recruiting
Houston, Texas, United States, 77030
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03519178     History of Changes
Other Study ID Numbers: C3661001
First Posted: May 8, 2018    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
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
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Triple Negative Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases