Study Using IMC-A12 (Cixutumumab) With or Without Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Failed a Treatment Regimen That Consisted of a Prior Anti-EGFR Therapy

NCT00503685 | Completed Phase 2 Results

• 4 other identifiers: 13936CP02-0657CP13-0605I5A-IE-JAEL
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 4

Brief Summary

Participants with metastatic Colorectal Cancer (mCRC) who have progressed on a prior Anti-epidermal growth factor receptor (EGFR) regimen randomized to receive IMC-A12 monotherapy or combination therapy with cetuximab to assess response, survival, durations of response, safety and tolerability as well as pharmacodynamics of IMC-A12 and cetuximab

Conditions

Colorectal Cancer

Keywords

Metastatic Colorectal Cancer with Disease Progression; Failed prior to Anti-EGFr Therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Complete Response (CR) or Partial Response [PR, Objective Response Rate (ORR)]

  ORR is the percentage of participants with a confirmed CR or PR, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR is calculated as a total number of participants with CR or PR from start of the treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.

  Start of randomization/treatment to date of objective progressive disease (PD) up to 28.3 weeks

Secondary Outcomes (12)

• Progression-Free Survival (PFS)

  Randomization/treatment to measured PD up to 28.3 weeks

• Overall Survival (OS)

  Randomization/treatment to date of death from any cause up to 26.9 months

• Duration of Stable Disease (SD)

  Time from randomization/treatment to first date of PD up to 28.3 weeks

• Duration of Overall Response

  Time of response to time of measured PD or death up to 161 days

• Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

  Randomization/treatment up to 26.9 months

Study Arms (3)

IMC-A12

EXPERIMENTAL

Administered every 2 weeks

Biological: IMC-A12

IMC-A12 + cetuximab

EXPERIMENTAL

Administered every 2 weeks

Biological: IMC-A12; Biological: cetuximab

IMC-A12 + cetuximab [Kirsten rat sarcoma (K-ras) wild-type]

EXPERIMENTAL

Participants who have experienced confirmed partial response (PR) or stable disease (SD) ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression are enrolled in this arm.

Biological: IMC-A12; Biological: cetuximab

Interventions

IMC-A12 BIOLOGICAL

10 milligrams/kilogram (mg/kg) intravenous infusion every 2 weeks.

Also known as: Cixutumumab, LY3012217

IMC-A12; IMC-A12 + cetuximab; IMC-A12 + cetuximab [Kirsten rat sarcoma (K-ras) wild-type]

cetuximab BIOLOGICAL

Participants will receive cetuximab 500 milligrams/square meter (mg/m²) intravenous over 2 hours every 2 weeks.

Also known as: Erbitux®

IMC-A12 + cetuximab; IMC-A12 + cetuximab [Kirsten rat sarcoma (K-ras) wild-type]

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant has histologically or cytologically-confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies
• The participant has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), measuring ≥ 2 centimeter (cm) on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
• The participant has clinical documentation of disease progression during treatment or within 6 weeks after receiving the last dose of a therapeutic regimen for metastatic disease containing an anti-EGFR-component (cetuximab or panitumumab). Toxicity or planned treatment break will not be regarded as adequate evidence of disease progression and such participants will not be eligible for this trial
• The participant has received at least one prior standard and/or investigational regimen for metastatic disease
• The participant is age ≥ 18 years
• The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 (Karnofsky ≥ 80%
• The participant has adequate hematologic function as defined by an absolute neutrophil count ≥ 1500/microliter (μL), hemoglobin ≥ 9 grams/deciliter (g/dL), and a platelet count ≥ 100,000/μL
• The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)
• The participant has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x the ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, and if on warfarin must have an INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or invading the rectal lumen, or known varices)
• The participant has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 milliliters/minute (mL/min) for participants with creatinine levels above the ULN, as well as urine protein ≤ 1+ on urine dipstick or routine urinalysis \[(UA), if urine dipstick/routine UA indicates ≥ 2+ protein, a 24-hour urine collection for protein must demonstrate \< 1000 milligrams (mg) of protein in 24 hours to allow participation in the study\]
• The participant has fasting serum glucose \< 120 milligrams/deciliter (mg/dL) or below the ULN
• The participant has a life expectancy of \> 3 months
• Because the teratogenicity of IMC-A12 (cixutumumab) is not known, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• The participant has the ability to understand and the willingness to sign a written informed consent document
• The participant has a tumor that is K-ras wild-type (absence of mutations at codon 12 or 13, as determined by the DxS K-ras Mutation Kit \[polymerase chain reaction (PCR)-based analysis\]).

You may not qualify if:

• The participant has received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or has not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have recovered to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 3.0 grade ≤ 2.
• The participant is receiving any other investigational agent(s).
• The participant has a history of treatment with other agents targeting the insulin-like growth factor receptor (IGFR).
• The participant has known brain or leptomeningeal metastases.
• The participant has a history of primary central nervous system tumors, seizures not well controlled with standard medical therapy, or history of stroke within 6 months prior to randomization.
• The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12 (cixutumumab).
• The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose \< 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition.
• The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• The participant is pregnant or lactating.
• The participant is known to be positive for infection with the human immunodeficiency virus.
• The participant is receiving therapy with immune modulators such as cyclosporine or tacrolimus.
• The participant has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected treated with no known active disease present and no treatment administered for the last 3 years.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (4)

ImClone Investigational Site

Los Angeles, California, 90095, United States

Location

ImClone Investigational Site

New Haven, Connecticut, 06520, United States

Location

ImClone Investigational Site

Buffalo, New York, 14263, United States

Location

ImClone Investigational Site

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

cixutumumab; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• E-mail: ClinicalTrials@ ImClone.com

  Eli Lilly and Company

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2007
• First Posted: July 19, 2007
• Study Start: June 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: June 6, 2018
• Results First Posted: June 6, 2018

Record last verified: 2018-05

Locations

US (4)