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A Study Of PF-05212384 In Combination With Other Anti-Tumor Agents and in Combination With Cisplatin in Patients With Triple Negative Breast Cancer in an Expansion Arm (TNBC)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01920061
First received: August 7, 2013
Last updated: July 24, 2017
Last verified: July 2017
  Purpose
This study will evaluate PF-05212384 (gedatolisib) PI3K/mTOR inhibitor)) in combination with either docetaxel, cisplatin or dacomitinib in select advanced solid tumors. The study will assess the safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer in order to determine the maximum tolerated dose in each combination. The cisplatin combination expansion portion will evaluate the anti tumor activity of PF 05212384 plus cisplatin in patients with TNBC in 2 separate Arms (Arm 1 and Arm 2).

Condition Intervention Phase
Neoplasm Drug: PF-05212384 (gedatolisib) Drug: Docetaxel Drug: Cisplatin Drug: Dacomitinib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 1b Open-label Three-arm Multi-center Study To Assess The Safety And Tolerability Of Pf-05212384 (pi3k/Mtor Inhibitor) In Combination With Other Anti-tumor Agents

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: up to 21 days ]
  • Expansion: Objective Tumor Response in mTNBC patients [ Time Frame: Baseline up to 18 months ]

Secondary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: pre-dose, 0.5 hrs, 1, 1.5 2, 4, 6, 24, 72, 96 and 168 hours post-dose on the first two dose of study treatment ]
    Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: pre-dose, 0.5 hrs, 1, 1.5 2, 4, 6, 24, 72, 96 and 168 hours post-dose around the first two dose of study treatment ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: pre-dose, 0.5 hrs, 1, 1.5 2, 4, 6, 24, 72, 96 and 168 hours post-dose around the first two dose of study treatment ]
  • Gene sequence data [ Time Frame: Paired biopsies collected at screening and on Cycle 2 Day 8 ]
    Expression of biomarkers eg. PIK3CA, KRAS

  • QTc interval [ Time Frame: Screening, Cycle 1 Day 2, Subsequent cycles on Day 1, 1 hour post infusion of PF-05212384, and end of treatment (Arm C only) ]
    QT interval corrected for heart rate using standard correction factors

  • Objective tumor response [ Time Frame: Baseline up to 18 months ]
    Time in weeks from the first documentation of objective tumor response to objective tumor progression or death according to RECIST

  • Levels of PI3K pathway protein biomarkers [ Time Frame: Paired biopsies collected at screening and on Cycle 2 Day 8 ]
    Expression of biomarkers eg. pAkt, PTEN, circulating insulin


Estimated Enrollment: 124
Actual Study Start Date: September 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A Drug: PF-05212384 (gedatolisib)
PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
Drug: Docetaxel
Docetaxel intravenous infusions once every 3 weeks starting at 75 mg/m^2
Experimental: Arm B Drug: PF-05212384 (gedatolisib)
PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
Drug: Cisplatin
Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2
Experimental: Arm C Drug: PF-05212384 (gedatolisib)
PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
Drug: Dacomitinib
Dacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg
Experimental: Expansion Arm 1 Drug: PF-05212384 (gedatolisib)
PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
Drug: Cisplatin
Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2
Experimental: Expansion Arm 2 Drug: PF-05212384 (gedatolisib)
PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
Drug: Cisplatin
Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2

  Eligibility

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

Inclusion Criteria:

Cisplatin Combination Expansion:

Arm 1:Patients with TNBC with no prior cytotoxic chemotherapy therapy in the metastatic setting; Arm 2: Patients with TNBC and one or two prior cytotoxic therapies in the metastatic setting.

  • Arm A: castrate resistant prostate cancer, advanced breast cancer, or non-small cell lunch cancer that are candidates for treatment with a docetaxel-based combination.
  • Arm B: Urothelial transitional cell cancer, triple negative breast cancer, ovarian cancer or non small cell lunch cancer that are candidates for a cisplatin-based combination.
  • Arm C: Her2+ breast cancer refractory to prior herceptin or lapatinib, her2+ esophagal-gastric cancer, head and neck squamous cell cancer, or non small cell lunch cancer that are candidates for treatment with a dacomitinib-based combination.
  • Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
  • Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1.
  • Adequate bone marrow, renal and liver function.

Exclusion Criteria:

  • Prior therapy for Cisplatin Combination Expansion:

    • Prior platinum (carboplatin or cisplatin) in either the adjuvant or metastatic setting;
    • Prior radiation to >25% bone marrow as estimated by the Investigator.
  • Patients with known symptomatic brain metastases.
  • Chemotherapy, radiotherapy, biologics or investigational agent within 4 weeks of the lead-in dose.
  • Major surgery within 4 weeks of the baseline disease assessments.
  • >2 prior regimens containing cytotoxic chemotherapy in the metastatic setting.
  • Active bacterial, fungal or viral infection.
  • Uncontrolled or significant cardiovascular disease.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01920061

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
United States, California
(IRB#13-000987) Ronald Reagan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Ronald Reagan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
UCLA Hematology Oncology Recruiting
Los Angeles, California, United States, 90095
UCLA Hematology/Oncology Recruiting
Los Angeles, California, United States, 90095
Westwood Bowyer Clinic Recruiting
Los Angeles, California, United States, 90095
Santa Monica UCLA Medical Center & Orthopaedic Hospital Recruiting
Santa Monica, California, United States, 90404
UCLA Hematology Oncology Recruiting
Santa Monica, California, United States, 90404
United States, Colorado
Anschutz Cancer Pavilion Active, not recruiting
Aurora, Colorado, United States, 80045
University of Colorado Denver CTO (CTRC) Active, not recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital Active, not recruiting
Aurora, Colorado, United States, 80045
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Harper Professional Building Recruiting
Detroit, Michigan, United States, 48201
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Fox Chase Cancer Center Active, not recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Medical University of South Carolina/ Univeristy Hospital Recruiting
Charleston, South Carolina, United States, 29425
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
MUSC Health East Cooper Recruiting
Mount Pleasant, South Carolina, United States, 29464
MUSC Specialty Care-North Recruiting
North Charleston, South Carolina, United States, 29406
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Centre Active, not recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Princess Margaret Cancer Centre Active, not recruiting
Toronto, Ontario, Canada, M5G 2M9
Italy
Istituto Europeo di Oncologia - Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative Recruiting
Milan, Italy, 20141
Istituto Regina Elena Struttura Complessa Oncologia Medica A Recruiting
Roma, Italy, 00144
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital Universitario 12 De Octubre Recruiting
Madrid, Spain, 28041
United Kingdom
University College London Hospital, NIHR UCLH Clinical Research Facility Recruiting
London, United Kingdom, W1T 7HA
Oxford Cancer Centre Active, not recruiting
Oxford, United Kingdom, OX3 7LE
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01920061     History of Changes
Other Study ID Numbers: B2151002
2013-001390-24 ( EudraCT Number )
Study First Received: August 7, 2013
Last Updated: July 24, 2017

Keywords provided by Pfizer:
Advanced cancer
solid tumors
PI3K
mTOR
PI3K/mTOR
metastatic
Triple Negative Breast Cancer (TNBC)

Additional relevant MeSH terms:
Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Cisplatin
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2017