Clinical trial NCT01937715: A Study Of PF-05212384 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI In Metastatic Colorectal Cancer
Official title: An Open-Label, Multi-Center, Randomized Phase 1b/2 Study Of PF-05212384 Plus 5-Fluorouracil-Leucovorin-Irinotecan (FOLFIRI) Versus Bevacizumab Plus FOLFIRI In Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Carcinoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-09-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open label Phase 1b/2 study in patients with metastatic colorectal carcinoma. The Phase 1b will identify the dose of the combination of PF-05212384 plus FOLFIRI. The randomized, two-arm Phase 2 portion will compare the efficacy and safety of PF-05212384 plus FOLFIRI to that of bevacizumab plus FOLFIRI.

The study population will consist of patients with mCRC previously treated with an oxaliplatin-based regimen in the first line setting or who have progressed within 6 months of the end of an adjuvant oxaliplatin-based regimen.


Eligibility criteria: Inclusion Criteria:

* Advanced colorectal carcinoma.
* Progression on prior oxaliplatin-containing regimen used in 1st line setting for mCRC or progression within 6 months of end of oxaliplatin-containing regimen in the adjuvant setting.
* Tumor tissue available at time of screening for molecular profiling.
* Adequate performance status.
* Adequate glucose control, bone marrow, kidney, liver, and heart function.

Exclusion Criteria:

* Participation in other studies involving investigational drug(s) (Phases 1-4) before the current study begins and/or during study participation.
* Prior irinotecan treatment.
* Prior radiation to the pelvis or abdomen in the metastatic or locally advanced setting.
* History of Gilbert's syndrome.
* Active brain metastases.
* Deep vein thrombosis in the preceding 2 months.
* History of interstitial lung disease.
* RAS (KRAS/NRAS) wild type mCRC not previously treated with an anti-EGFR containing regimen (unless contraindicated or not considered standard practice per clinical site or country guidelines).

Primary outcomes:
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy
timeFrame: Day 1 up to Day 28
measure: Progression-Free Survival (PFS)
timeFrame: Baseline (Day 1) up to disease progression or death whichever occurred first (up to 18 months)
Secondary outcomes:
measure: Number of Participants With Best Overall Response (Phase 1B)
timeFrame: Every 8 weeks from Cycle 1 Day 1 until 28 days of last dose
measure: Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
timeFrame: Baseline up to final study evaluation (within 28 days of last dose)
measure: Number of Participants With All Causality AEs by System Organ Class (SOC)
timeFrame: Baseline up to final study evaluation (within 28 days of last dose)
measure: Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
timeFrame: Baseline up to final study evaluation (within 28 days of last dose)
measure: Number of Participants With Hematological Test Abnormalities
timeFrame: Day 1 and Day 15 of each cycle
measure: Number of Participants With Coagulation Test Abnormalities
timeFrame: Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles
measure: Number of Participants With Chemistry Test Abnormalities
timeFrame: Day 1 and Day 15 of each cycle
measure: Number of Participants With Urinalysis Test Abnormalities
timeFrame: Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles
measure: Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil
timeFrame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil
timeFrame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan
timeFrame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
measure: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan
timeFrame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
measure: Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan
timeFrame: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
measure: Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
timeFrame: Baseline, Cycle 1 Day 1, and Cycle 2 Day 2
measure: Number of Participants With Expression of Gene Sequences or Gene Amplications in Biopsied Tumor Tissue
timeFrame: Baseline and Cycle 2 Day 17
measure: Number of Participants With Gene and/or Protein Expression Biomarkers Relating to the PI3K and/or mTOR Pathway Activation in Biopsied Tumor Tissue
timeFrame: Baseline and Cycle 2 Day 17
measure: Number of Participants With Best Overall Response (Phase 2)
timeFrame: Day 1 up to Day 28
measure: Duration of Response (Phase 2)
timeFrame: Day 1 to Day 28
measure: Overall Survival (Phase 2)
timeFrame: Day 1 up to Day 28
measure: Number of Participants With Evidence of Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue (Phase 2)
timeFrame: Baseline and Cycle 2 Day 17
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C) (Phase 2)
timeFrame: Day 1 of each cycle
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
state: California
city: Irvine
country: United States
facility: UCLA Hematology Oncology
state: California
city: Los Angeles
country: United States
facility: Drug Management Only: UCLA West Medical Pharmacy, Attn Steven L. Wong, Pharm .D.
state: California
city: Los Angeles
country: United States
facility: Drug Management Only: UCLA West Medical Pharmacy
state: California
city: Los Angeles
country: United States
facility: UCLA West Medical Pharmacy, Att: Steven L. Wong, Pharm D.
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Regan UCLA Medical Center, Drug Information Center
state: California
city: Los Angeles
country: United States
facility: TRIO-US Central Administration, Regulatory Management Only
state: California
city: Los Angeles
country: United States
facility: TRIO-US Central Administration
state: California
city: Los Angeles
country: United States
facility: TRIO_US
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology Oncology Administrative Address
state: California
city: Los Angeles
country: United States
facility: Westwood Bowyer Clinic, Peter Morton Medical Building
state: California
city: Northridge
country: United States
facility: West Valley Hematology/Oncology Med Group
state: California
city: Pasadena
country: United States
facility: UCLA/Pasadena Healthcare
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Santa Monica Medical Center & Orthopaedic Hospital
state: California
city: Valencia
country: United States
facility: UCLA/Santa Clarita Valley Cancer Center
state: California
city: Westlake Village
country: United States
facility: UCLA Cancer Center
state: California
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada Research Department
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of NV
state: Nevada
city: Las Vegas
country: United States
facility: COmprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers for Nevada
state: Nevada
city: Cleveland
country: United States
facility: Metrohealth Medical Center
state: Ohio
city: Spartanburg
country: United States
facility: Medical Group of the Carolinas - Hematology Spartanburg
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Richland
country: United States
facility: Kadlec Medical Center
state: Washington
city: Richland
country: United States
facility: Outpatient Imaging Center
state: Washington
city: Seattle
country: United States
facility: Investigational Drug Services
state: Washington
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Spokane Valley
country: United States
facility: Spokane Valley Cancer Center
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates, PS
state: Washington
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: