A Study Of PF-05212384 In Combination With Other Anti-Tumor Agents

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01920061
First received: August 7, 2013
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

This study will evaluate PF-05212384 (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.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Gene sequence data [ Time Frame: Paired biopsies collected at screening and on Cycle 2 Day 8 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    QT interval corrected for heart rate using standard correction factors

  • Objective tumor response [ Time Frame: Baseline up to 18 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Expression of biomarkers eg. pAkt, PTEN, circulating insulin


Estimated Enrollment: 85
Study Start Date: September 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A Drug: PF-05212384
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
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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, 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:

  • 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

Locations
United States, California
Pfizer Investigational Site Recruiting
Los Angeles, California, United States, 90095
Pfizer Investigational Site Recruiting
Santa Monica, California, United States, 90404
United States, Colorado
Pfizer Investigational Site Recruiting
Aurora, Colorado, United States, 80045
United States, Massachusetts
Pfizer Investigational Site Recruiting
Boston, Massachusetts, United States, 02215
Pfizer Investigational Site Recruiting
Boston, Massachusetts, United States, 02115
United States, Michigan
Pfizer Investigational Site Recruiting
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Pfizer Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Pfizer Investigational Site Recruiting
Charleston, South Carolina, United States, 29425
Canada, British Columbia
Pfizer Investigational Site Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Pfizer Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Italy
Pfizer Investigational Site Recruiting
Milano, Italy, 20141
Pfizer Investigational Site Recruiting
Roma, Italy, 00144
Spain
Pfizer Investigational Site Recruiting
Barcelona, Spain, 08035
Pfizer Investigational Site Recruiting
Barcelona, Spain, 8035
Pfizer Investigational Site Not yet recruiting
Madrid, Spain, 28041
United Kingdom
Pfizer Investigational Site Recruiting
London, United Kingdom, NW1 2BU
Pfizer Investigational Site Recruiting
London, United Kingdom, WC1E 6BT
Pfizer Investigational Site Recruiting
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01920061     History of Changes
Other Study ID Numbers: B2151002
Study First Received: August 7, 2013
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Advanced cancer
solid tumors
PI3K
mTOR
PI3K/mTOR
metastatic

Additional relevant MeSH terms:
Neoplasms
Docetaxel
Antineoplastic Agents
Cisplatin
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014