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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.
Verified December 2017 by Pfizer
Sponsor:
ClinicalTrials.gov Identifier:
NCT01920061
First Posted: August 9, 2013
Last Update Posted: December 14, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
  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 10, 2013
Estimated Study Completion Date: December 18, 2019
Estimated Primary Completion Date: December 18, 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

Information from the National Library of Medicine

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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
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): NCT01920061


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

  Show 32 Study Locations
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 )
First Submitted: August 7, 2013
First Posted: August 9, 2013
Last Update Posted: December 14, 2017
Last Verified: December 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