A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of Participants With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00845039
• Date of registration: 10/02/2009
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of Participants With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab FC-4
• Scientific title: A Randomized Phase II Clinical Trial Investigating Irinotecan Plus Cetuximab With or Without Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody (IMC-A12) for the Treatment of Patients With Metastatic K-Ras Wild Type Carcinoma of the Colon or Rectum That Has Progressed on Oxaliplatin and Bevacizumab Given as First-Line Therapy
• Date of first enrolment: May 2009
• Target sample size: 4
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00845039
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• 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)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

Inclusion Criteria:

- Must consent to be in the study and must have signed and dated Institutional Review
Board (IRB)-approved consent forms conforming to federal and institutional guidelines
for the pre-entry tumor sample submission for central K-RAS testing and for the study
treatment

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
2

- Must have metastatic CRC

- The CRC tumor or metastatic tumor must be v-Ki-ras2 Kirsten rat sarcoma viral oncogene
homolog gene (K-RAS) wild-type as determined by central testing

- Must be documented disease progression during first-line therapy containing both
oxaliplatin and bevacizumab

- Most recent treatment regimen must have ended =21 days prior to randomization, and
clinically significant side effects associated with previous therapy must have
resolved to =Grade 1 with the exception of neuropathy which must have resolved to
=Grade 2

- Imaging of the chest, abdomen and pelvis with computed tomography (CT) scan or
magnetic resonance imaging (MRI) must be performed within 3 weeks prior to
randomization

- Must have measurable disease, defined as at least 1 lesion outside a previous
radiation therapy (RT) field that can be accurately measured in at least 1 dimension
as =20 millimeters (mm) with conventional techniques or as =10mm with 5mm cuts using a
spiral CT scan

- Evidence of adequate bone marrow function: absolute neutrophil (ANC) =1200 cubed
millimeters (mm³), hemoglobin =9 grams per deciliter (g/dL), platelets =100,000 mm³

- Evidence of adequate hepatic function. If no liver metastases: aspartate
aminotransferase (AST) =2.5 times (x) upper limit of normal (ULN), total bilirubin
=1.5 x ULN for the lab. In the presence of liver metastases: AST =5.0 x ULN, total
bilirubin =1.5 x ULN for the lab

- Serum creatinine must be =1.5 x ULN for the lab

- Must have a fasting blood glucose <126 milligrams/deciliter (mg/dL). Fasting is
defined as no caloric intake for at least 8 hours

Exclusion Criteria:

- Life expectancy less than 12 weeks

- Diagnosis of anal or small bowel carcinoma

- Tumor that is considered by the surgeon to be amenable to complete resection

- Previous RT to >25% of bone marrow

- RT to sites of measurable disease chosen as target lesions

- Radiological evidence and/or clinical signs or symptoms of central nervous system
(CNS) metastases

- Any of the following conditions and events: uncontrolled hypertension, defined as
systolic blood pressure (BP) >150 millimeters of mercury (mmHg) or diastolic BP >100
mmHg with or without antihypertensive medication (participants with hypertension that
is well-controlled on medication are eligible); unstable angina within 6 months before
randomization; New York Heart Association (NYHA) Class III or IV cardiac disease;
myocardial infarction (MI) within 6 months before randomization; symptomatic
arrhythmia; CNS cerebrovascular ischemia [transient ischemic attack (TIA) or stroke]
within 6 months before randomization

- Other malignancies unless the participant is considered to be disease-free and has
completed therapy for the malignancy =12 months prior to randomization. Participants
with the following cancers are eligible if diagnosed and treated within the past 12
months: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ,
and basal cell and squamous cell carcinoma of the skin

- Serious or non-healing wound, skin ulcers, or bone fracture

- Any significant bleeding unless the source of bleeding has been resected

- History of bleeding diathesis or coagulopathy (participants on stable anticoagulant
therapy are eligible)

- Any evidence of active infection

- Active inflammatory bowel disease

- Grade 3 or 4 diabetes mellitus as defined by National Cancer Institute's (NCI's)
Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 pancreatic endocrine:
glucose intolerance (participants with diabetes controlled with diet and/or oral
medications are eligible)

- Symptomatic interstitial pneumonitis or definitive evidence of interstitial
pneumonitis described on CT scan or chest x-ray in asymptomatic participants

- Any other serious concomitant medical condition that, in the opinion of the
investigator, would compromise the safety of the participant or compromise the
participant's ability to participate in the study

- Previous hypersensitivity reaction to monoclonal antibodies

- Previous treatment with irinotecan, cetuximab, or any agent specifically targeting
insulin-like growth factor (IGF) receptors

- Treatment with an investigational drug within 30 days prior to randomization

- Pregnancy or lactation at the time of participant entry

- Psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude the participant from meeting the study requirements



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Colon Cancer

Rectal Cancer

Intervention(s)

Biological: IMC-A12 (cixutumumab)

Drug: Irinotecan

Biological: Cetuximab

Primary Outcome(s)

Progression-Free Survival (PFS) Rate at 18 Weeks [Time Frame: Approximately 18 Weeks]

Secondary Outcome(s)

Toxicity of the Irinotecan + Cetuximab + IMC-A12 Regimen [Time Frame: Randomization up to 26.3 months]

Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)] [Time Frame: Randomization up to 26.3 months]

The Number of Participants Who Had a Complete Resection/Ablation of Metastases With no Evidence of Disease Remaining (Resection Rate) [Time Frame: Randomization up to 26.3 months]

Change in Behavioral and Health Outcomes [BAHO] Quality of Life (QoL) Questionnaire [Time Frame: Baseline, after Cycle 3 (14-day cycle), study discontinuation 30-day follow-up (up to 26.3 months)]

Progression Free Survival (PFS) Over Entire Duration [Time Frame: Randomization up to 26.3 months]

Serum Anti-IMC-A12 Antibody Assessment [Time Frame: Prior to infusion at Cycles 1, 4, 7 (2-week cycles), and 4 to 6 weeks following discontinuation of treatment IMC-A12 up to 77 weeks]

Overall Survival (OS) [Time Frame: Randomization up to 26.3 months]

Post-treatment Serum Levels of IMC-A12 in Participants Receiving IMC-A12 [Time Frame: Prior to infusion at Cycles 1, 4, 7 (2-week cycles), and 4 to 6 weeks following discontinuation of treatment IMC-A12 up to 77 weeks]

Secondary ID(s)

CP13-0708

13928

NSABP FC-4

I5A-IE-JAED

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

NSABP Foundation Inc

Results

• Results available: Yes
• Date Posted: 01/06/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00845039