Clinical trial NCT01111604: A Study of Ramucirumab or Icrucumab in Colorectal Cancer
Official title: An Open-label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of 5 FU/FA and Oxaliplatin (Modified FOLFOX 6) in Combination With Ramucirumab or IMC-18F1 or Without Investigational Therapy as Second Line Therapy in Patients With Metastatic Colorectal Cancer Following Disease Progression on First Line Irinotecan-based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colon Cancer
Rectal Cancer
Keywords: Colonic Neoplasms
Rectal Neoplasms
Adenocarcinoma
Antibodies, Monoclonal
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-04-27
Enrollment: 158
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 this study is to determine if participants with metastatic colorectal cancer live longer without their cancer progressing when treated with standard chemotherapy, standard chemotherapy plus ramucirumab, or standard chemotherapy plus icrucumab.

Detailed description: The purpose of this study is to evaluate the progression-free survival (PFS) in participants with metastatic colorectal cancer when treated with 1 of 3 modified FOLFOX-6 (folinic acid \[FA\] + fluorouracil \[5-FU\] + oxaliplatin \[mFOLFOX-6\])-based regimens, as second-line therapy.

During 2010, there has been an identified shortage of injectable folinic acid (FA) in the United States. Levo-folinic acid (LFA) will be allowed as a substitute for FA in the mFOLFOX-6 chemotherapy regimen in circumstances in which FA is not available, to facilitate continuity of participant care.

Eligibility criteria: Inclusion Criteria:

* Disease progression on an irinotecan-based first-line chemotherapy regimen (ie FOLFIRI or CAPIRI \[capecitabine + irinotecan\], with or without bevacizumab)
* Age ≥ 18 years
* Life expectancy of ≥ 6 months
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry
* Agrees to adequate contraception during the study period and for 12 weeks after the last dose of study medication
* Provided signed informed consent

Exclusion Criteria:

* Has received prior oxaliplatin-based chemotherapy for locally advanced unresectable or metastatic Colorectal Cancer (CRC) (Prior oxaliplatin-based adjuvant chemotherapy is allowed if the last dose of oxaliplatin was administered \> 12 months prior to randomization)
* Has documented and/or symptomatic brain or leptomeningeal metastases
* Has an ongoing or active infection, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders
* On chronic non-topical corticosteroid treatment. A participant discontinuing such treatment \> 3 months prior to randomization is eligible
* Has uncontrolled or poorly controlled hypertension on a standard regimen of antihypertensive therapy
* Has a concurrent active malignancy. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for \> 3 years
* If female, is pregnant (confirmed by serum beta human chorionic gonadotropin \[βHCG\] test) or lactating
* Has received a prior autologous or allogeneic organ or tissue transplantation
* Has undergone major surgery within 28 days prior to randomization
* Has had a serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
* Has an elective or planned major surgery to be performed during the course of the trial
* Has a history of inflammatory bowel disease requiring pharmacological and/or surgical intervention in the 12 months prior to randomization

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline until Disease Progression or Death from Any Cause (Up to 95 Weeks)
Secondary outcomes:
measure: Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
timeFrame: Baseline until Disease Progression (Up to 95 Weeks)
measure: Overall Survival (OS)
timeFrame: Baseline Until Death from Any Cause (Up to 163 Weeks)
measure: Duration of Response (DoR)
timeFrame: Criteria First Met for CR or PR until Disease Progression or Death from Any Cause (Up to 95 Weeks)
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) at Cycle 5
timeFrame: Cycle 5, 1 Hour Post End of Infusion
measure: Pharmacokinetics (PK): Trough Serum Concentrations (Ctrough) at Cycle 5
timeFrame: Cycle 5, Prior to Infusion
measure: Maximum Concentration (Cmax) at Day 8
timeFrame: Day 8 (cycles 1 and 5)
measure: Maximum Concentration (Cmax) at Day 15
timeFrame: Day 15 (Cycles 1 and 5)
measure: Minimum Concentration (Cmin) at Day 1
timeFrame: Day 1 (cycles 1, 5, 9, and 13)
measure: Minimum Concentration (Cmin) at Day 4
timeFrame: Day 4 (cycles 1 and 5)
measure: Minimum Concentration (Cmin) at Day 8
timeFrame: Day 8 (cycles 1 and 5)
measure: Minimum Concentration (Cmin) at Day 15
timeFrame: Day 15 (cycles 1 and 5)
measure: Number of Participants With Serum Ramucirumab Antibody Assessment
timeFrame: 31 Weeks
measure: Serum Anti-Icrucumab Antibody Assessment
timeFrame: 31 Weeks
measure: Number of Participants With Adverse Events
timeFrame: Baseline up to 165 weeks
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Columbia
country: United States
facility: ImClone Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: ImClone Investigational Site
state: Tennessee
city: Calgary
country: Canada
facility: ImClone Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: ImClone Investigational Site
state: Alberta
city: Kelowna
country: Canada
facility: ImClone Investigational Site
state: British Columbia
city: Surrey
country: Canada
facility: ImClone Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: ImClone Investigational Site
state: British Columbia
city: Halifax
country: Canada
facility: ImClone Investigational Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: London
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Oshawa
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: ImClone Investigational Site
state: Quebec
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: Moore M, Gill S, Asmis T, Berry S, Burkes R, Zbuk K, Alcindor T, Jeyakumar A, Chan T, Rao S, Spratlin J, Tang PA, Rothenstein J, Chan E, Bendell J, Kudrik F, Kauh J, Tang S, Gao L, Kambhampati SR, Nasroulah F, Yang L, Ramdas N, Binder P, Strevel E. Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy. Ann Oncol. 2016 Dec;27(12):2216-2224. doi: 10.1093/annonc/mdw412. Epub 2016 Oct 11.