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)
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
2 other identifiers
interventional
110
5 countries
29
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2013
Longer than P75 for phase_1
29 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 7, 2013
CompletedFirst Posted
Study publicly available on registry
August 9, 2013
CompletedStudy Start
First participant enrolled
September 10, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 8, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 8, 2020
CompletedResults Posted
Study results publicly available
October 7, 2021
CompletedSeptember 13, 2022
August 1, 2022
6.3 years
August 7, 2013
January 6, 2021
August 20, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C
DLT was defined as any of the following adverse events (AEs) attributable to the combination: (1) hematologic: grade 4 neutropenia lasting \>7 days; febrile neutropenia; grade \>=3 neutropenia with infection; grade 3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade \>=2 pneumonitis; grade\>=3 toxicities, except pneumonitis, and excluding those that had not been maximally treated; persistent, intolerable toxicities which resulted in the failure to deliver at least 3 of the 4 doses of PF-05212384 for Arms A and B or at least 3 of the 4 doses of PF-05212384 and 75% of dacomitinib for Arm C during the first cycle; the persistent, intolerable toxicities which result in delay of the start of the second cycle by more than 2 weeks relative to the scheduled start; in an asymptomatic participant, the grade 3 QTc prolongation persists after correction of any reversible causes.
Up to 21 days
Percentage of Participants With Objective Response - Arm B Expansion
Percentage of participants with objective response based on the assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm) and no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
Cycle 1 Day 1 up to 18 months
Secondary Outcomes (67)
Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion
From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) - Arms A, B, C and B Expansion
From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology
From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation
From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry
From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
- +62 more secondary outcomes
Study Arms (5)
Arm A
EXPERIMENTALArm B
EXPERIMENTALArm C
EXPERIMENTALExpansion Arm 1
EXPERIMENTALExpansion Arm 2
EXPERIMENTALInterventions
PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m\^2
Dacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (29)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095, United States
UCLA Hematology Oncology
Los Angeles, California, 90095, United States
Westwood Bowyer Clinic
Los Angeles, California, 90095, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115, United States
Santa Monica UCLA Medical Center & Orthopaedic Hospital
Santa Monica, California, 90404, United States
UCLA Hematology Oncology
Santa Monica, California, 90404, United States
University of Colorado Denver CTO (CTRC)
Aurora, Colorado, 80045, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Harper Professional Building
Detroit, Michigan, 48201, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Medical University of South Carolina/ University Hospital
Charleston, South Carolina, 29425, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
MUSC SCTR Research
Charleston, South Carolina, 29425, United States
MUSC Health East Cooper
Mt. Pleasant, South Carolina, 29464, United States
MUSC Specialty Care-North
North Charleston, South Carolina, 29406, United States
British Columbia Cancer Agency - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6, Canada
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9, Canada
Istituto Europeo di Oncologia - Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative
Milan, MI, 20141, Italy
Istituto Regina Elena Struttura Complessa Oncologia Medica A
Roma, RM, 00144, Italy
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
University College London Hospital, NIHR UCLH Clinical Research Facility
London, W1T 7HA, United Kingdom
Oxford Cancer Centre
Oxford, OX3 7LE, United Kingdom
Related Publications (1)
Curigliano G, Shapiro GI, Kristeleit RS, Abdul Razak AR, Leong S, Alsina M, Giordano A, Gelmon KA, Stringer-Reasor E, Vaishampayan UN, Middleton M, Olszanski AJ, Rugo HS, Kern KA, Pathan N, Perea R, Pierce KJ, Mutka SC, Wainberg ZA. A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer. Br J Cancer. 2023 Jan;128(1):30-41. doi: 10.1038/s41416-022-02025-9. Epub 2022 Nov 5.
PMID: 36335217DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer, Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 7, 2013
First Posted
August 9, 2013
Study Start
September 10, 2013
Primary Completion
January 8, 2020
Study Completion
January 8, 2020
Last Updated
September 13, 2022
Results First Posted
October 7, 2021
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will not share
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.