Clinical trial NCT00460603: Study With AG-013736 Combined With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer
Official title: A Randomized Phase 2 Study Of The Anti-Angiogenesis Agent AG-013736 In Combinations With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer Preceded By A Phase 1 Portion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Neoplasms
Keywords: GI neoplasms (phase 1)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-04-16
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the safety and efficacy of AG-013736 in combination with other standard of care medication in patients with first line metastatic colorectal cancer.


Eligibility criteria: Inclusion Criteria:

* (Phase 1) Patients with any solid/GI tumor who have had no more than 1 previous chemotherapy for greater than 3 months prior to enrollment
* (Phase 2) Patients with locally advanced or metastatic colorectal cancer (CRC) previously untreated with any systemic therapy.
* Patients treated with adjuvant chemotherapy (with radiation) will be eligible if last treatment was \> 12 months prior to enrollment,
* Patients must have measurable disease by RECIST and if any history of hypertension, it must be controlled with medication.

Exclusion Criteria:

* Prior system therapy for advanced CRC (Ph 2 portion only)
* Prior treatment with anti-angiogenesis agent such as bevacizumab or VEGF inhibitors.
* Prior irradiation of greater than 25% of bone marrow (whole pelvis = 25%)
* Prior radiation, major surgery, or investigational agent within 4 weeks of study entry except palliative radiotherapy to non-target, metastatic lesions. Minor surgeries should be completed \> 2 weeks of enrollment and be fully recovered from any procedure.

Primary outcomes:
measure: Percentage of Participants With Objective Response: Phase 2
timeFrame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
Secondary outcomes:
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6 and 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
measure: Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
measure: Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
measure: Apparent Oral Clearance (CL/F) For Axitinib: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
measure: Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Minimum Observed Plasma Trough Concentration (Cmin) For Oxaliplatin: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Clearance (CL) For Oxaliplatin: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1
timeFrame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1
timeFrame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1
timeFrame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Minimum Observed Plasma Trough Concentration (Cmin) For 5-Fluorouracil: Phase 1
timeFrame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Clearance (CL) For 5-Fluorouracil: Phase 1
timeFrame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1
timeFrame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Minimum Observed Plasma Trough Concentration (Cmin) For Irinotecan: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Clearance (CL) For Irinotecan: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1
timeFrame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Minimum Observed Plasma Trough Concentration (Cmin) For Bevacizumab: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Clearance (CL) For Bevacizumab: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1
timeFrame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1
measure: Duration of Response (DR): Phase 2
timeFrame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
measure: Progression-Free Survival (PFS): Phase 2
timeFrame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
measure: Time to Treatment Failure (TTF): Phase 2
timeFrame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)
measure: Overall Survival (OS): Phase 2
timeFrame: Every 3 months after discontinuation of study treatment until death due to any cause or 1 year after randomization of the last participant
measure: Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2
timeFrame: Cycle 1 Day 1 (baseline), every 2 weeks for the first 2 months (Cycle 2 Day 1 [C2D1], Cycle 3 Day 1, and Cycle 4 Day 1) then monthly thereafter starting Cycle 6 Day 1, and 28 days after the last dose
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Mobile
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Antioch
country: United States
facility: Pfizer Investigational Site
state: California
city: Colton
country: United States
facility: Pfizer Investigational Site
state: California
city: Corona
country: United States
facility: Pfizer Investigational Site
state: California
city: Gilroy
country: United States
facility: Pfizer Investigational Site
state: California
city: Glendora
country: United States
facility: Pfizer Investigational Site
state: California
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: LaJolla
country: United States
facility: Pfizer Investigational Site
state: California
city: Pasadena
country: United States
facility: Pfizer Investigational Site
state: California
city: Pleasant Hill
country: United States
facility: Pfizer Investigational Site
state: California
city: Pomona
country: United States
facility: Pfizer Investigational Site
state: California
city: Rancho Cucamonga
country: United States
facility: Pfizer Investigational Site
state: California
city: Rancho Mirage
country: United States
facility: Pfizer Investigational Site
state: California
city: Redlands
country: United States
facility: Pfizer Investigational Site
state: California
city: San Diego
country: United States
facility: Pfizer Investigational Site
state: California
city: San Diego
country: United States
facility: Pfizer Investigational Site
state: California
city: San Leandro
country: United States
facility: Pfizer Investigational Site
state: California
city: West Covina
country: United States
facility: Pfizer Investigational Site
state: California
city: Auroa
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Boulder
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Colorado Springs
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Denver
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Denver
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Lakewood
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Littleton
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Lone Tree
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Longmont
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Parker
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Thornton
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Ocala
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Stuart
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Pfizer Investigational Site
state: Georgia
city: Beech Grove
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Jeffersonville
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Muncie
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Kansas City
country: United States
facility: Pfizer Investigational Site
state: Kansas
city: Overland Park
country: United States
facility: Pfizer Investigational Site
state: Kansas
city: Louisville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Shelbyville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Pfizer Investigational Site
state: Louisiana
city: Brownstone
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Dearborn
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: West Bloomfield
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Kansas City
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Kansas City
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Kansas City
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Lee's Summit
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Grand Island
country: United States
facility: Pfizer Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: Pfizer Investigational Site
state: Nevada
city: Summit
country: United States
facility: Pfizer Investigational Site
state: New Jersey
city: Albany
country: United States
facility: Pfizer Investigational Site
state: New York
city: Albany
country: United States
facility: Pfizer Investigational Site
state: New York
city: Amsterdam
country: United States
facility: Pfizer Investigational Site
state: New York
city: Hudson
country: United States
facility: Pfizer Investigational Site
state: New York
city: Latham
country: United States
facility: Pfizer Investigational Site
state: New York
city: Rexford
country: United States
facility: Pfizer Investigational Site
state: New York
city: Troy
country: United States
facility: Pfizer Investigational Site
state: New York
city: Kernersville
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Lexington
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Mount Airy
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: North Wilkesboro
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Pollocksville
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Winston Salem
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Oregon City
country: United States
facility: Pfizer Investigational Site
state: Oregon
city: Portland
country: United States
facility: Pfizer Investigational Site
state: Oregon
city: Portland
country: United States
facility: Pfizer Investigational Site
state: Oregon
city: Portland
country: United States
facility: Pfizer Investigational Site
state: Oregon
city: Tualatin
country: United States
facility: Pfizer Investigational Site
state: Oregon
city: West Reading
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Easley
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Seneca
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Franklin
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Gallatin
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Hermitage
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Lebanon
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Smyrna
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Houston
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Tyler
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Ogden
country: United States
facility: Pfizer Investigational Site
state: Utah
city: Everett
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Kennewick
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Vancouver
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Vancouver
country: United States
facility: Pfizer Investigational Site
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Hoh CK, Burris HA 3rd, Bendell JC, Tarazi J, Rosbrook B, Kim S, Infante JR, Reid TR. Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours. Br J Cancer. 2014 Feb 18;110(4):875-81. doi: 10.1038/bjc.2013.806. Epub 2014 Jan 14.
citation: Infante JR, Reid TR, Cohn AL, Edenfield WJ, Cescon TP, Hamm JT, Malik IA, Rado TA, McGee PJ, Richards DA, Tarazi J, Rosbrook B, Kim S, Cartwright TH. Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: a randomized phase 2 study. Cancer. 2013 Jul 15;119(14):2555-63. doi: 10.1002/cncr.28112. Epub 2013 Apr 19.