Clinical trial NCT00192075: A Randomized Trial of Avastin + Gemcitabine + 5-Fluorouracil (5FU)/Folinic Acid Versus Avastin + Oxaliplatin + 5FU/Folinic Acid in Metastatic Colorectal Cancer
Official title: A Multicenter, Randomized Phase II Trial of Avastin Plus Gemcitabine Plus 5FU/Folinic Acid (A + FFG) vs. Avastin Plus Oxaliplatin Plus 5FU/Folinic Acid (A + FOLFOX 4) as Therapy for Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2005-09-19
Enrollment: 84
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: The purpose of the study is to describe the tumor response rates for the two regimens being studied, and to determine how long patients live after receiving the treatment, how long patients are without return of their disease after they receive treatment, and how long the response they get from the treatment lasts. The amount and type of side effects/toxicities of each regimen will also be evaluated. The regimen including Oxaliplatin + 5FU/Folinic Acid is a current standard of care.


Eligibility criteria: Inclusion Criteria:

* Patients must have a histological or cytological diagnosis of the colon or rectum with Stage III unresectable or Stage IV disease.
* Urinalysis or Urine dipstick for proteinuria of less than 1+ (i.e. either 0 or trace). If urine dipstick is greater than 1+, the 24 hour urine protein must demonstrate less than 500 mg of protein in 24 hours to allow participation.
* No prior chemotherapy, immunotherapy, or hormonal treatment for metastatic disease is acceptable. However, one prior neo-adjuvant or adjuvant treatment is acceptable, including Capecitabine, Camptothecin-11 (CPT-11), 5 Fluorouracil/Leucovorin (5FU/LV) or Radiation containing regimens, (but no Oxaliplatin), and only if progression \> 6 months since last adjuvant treatment.
* Prior radiation therapy, including radiation to the whole pelvis, is allowed (Cristy and Eckerman 1987) and patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Prior palliative radiation therapy given to a non-measurable diagnostic site is acceptable if given \> 4 weeks prior to treatment or if other non-irradiated measurable disease is present.
* No known central nervous system (CNS) metastasis.

Exclusion Criteria:

* Histology other than adenocarcinoma
* Tumors that demonstrate free perforation as manifested by free air or free fluid in the abdomen. Patients with walled-off perforation are eligible.
* Gastroduodenal ulcer determined as active by endoscopy.
* Invasive procedures defined as follows; major surgical procedures, open biopsy, or significant traumatic injury within 28 days prior to randomization, anticipation of need for major surgical procedure during the course of study, core biopsy or other minor procedure within 7 days prior to registration.
* Following cardiac condition; New York Heart Association (NYHA) Class III or IV, myocardial infarction (MI) within 6 months, unstable angina within 6 months and current symptomatic arrhythmia.

Primary outcomes:
measure: Tumor Response by Response Evaluation Criteria In Solid Tumors (RECIST)
timeFrame: baseline to measured progressive disease (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
Secondary outcomes:
measure: Time to Progressive Disease
timeFrame: randomization to the date of first documented disease progression or death due to disease under study, whichever comes first (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
measure: Progression-Free Survival
timeFrame: randomization to the first date of progression or death from any cause (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
measure: Overall Survival
timeFrame: randomization to the date of death from any cause (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
measure: Duration of Response
timeFrame: date of first response until the first date of documented progression or death from any cause (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
Other outcomes:
measure: Tumor Response - Avastin Subgroup
timeFrame: baseline to measured progressive disease (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
measure: Time to Progressive Disease - Avastin Subgroup
timeFrame: randomization to the date of first documented disease progression or death due to disease under study, whichever comes first (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
measure: Progression-Free Survival - Avastin Subgroup
timeFrame: randomization to the first date of progression or death from any cause (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
measure: Survival at 12 Months and 24 Months - Avastin Subgroup
timeFrame: randomization to the date of death from any cause (up to 24 months)
measure: Toxicity - Avastin Subgroup
timeFrame: every cycle (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
measure: Duration of Response - A+FOLFOX4 - Avastin Subgroup
timeFrame: date of first response until the first date of documented progression or death from any cause (every 7-8 weeks for 2 cycles, monthly for 3 months, every other month for 6 months, then every 3 months up to 4.4 years)
Locations:
city: Tucson
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Arizona
city: Beverly Hills
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: California
city: Palm Springs
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: California
city: Stockton
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: California
city: Kansas City
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Kansas
city: Springfield
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Massachusetts
city: Lansing
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Michigan
city: Tupelo
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Mississippi
city: Bronx
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: New York
city: Stonybrook
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: New York
city: Burlington
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: North Carolina
city: Cincinnati
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Ohio
city: Springfield
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Ohio
city: Marshfield
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Wisconsin
city: Milwaukee
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Wisconsin
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Madajewicz S, Waterhouse DM, Ritch PS, Khan MQ, Higby DJ, Leichman CG, Malik SK, Hentschel P, Gill JF, Zhao L, Nicol SJ. Multicenter, randomized phase II trial of bevacizumab plus folinic acid, fluorouracil, gemcitabine (FFG) versus bevacizumab plus folinic acid, fluorouracil, oxaliplatin (FOLFOX4) as first-line therapy for patients with advanced colorectal cancer. Invest New Drugs. 2012 Apr;30(2):772-8. doi: 10.1007/s10637-010-9598-9. Epub 2010 Dec 1.