Colon Cancer, Rectal Cancer
Conditions
Keywords
Tumors, Antibodies, Monoclonal, Colorectal Neoplasms, Metastatic K-RAS Wild-Type Carcinoma of the Colon or Rectum
Brief summary
The purpose of this study is to determine the value of adding IMC-A12 to irinotecan and cetuximab in participants with metastatic colorectal cancer (CRC).
Detailed description
The purpose of this study is to determine the value of adding IMC-A12 to irinotecan + cetuximab in improving progression-free survival (PFS) at 18 weeks from the date of randomization for participants with metastatic Kirsten Rat Sarcoma (K-RAS) wild-type CRC that has progressed on an oxaliplatin/bevacizumab-containing regimen.
Interventions
BIOLOGICALCetuximab
Cetuximab 500 mg/m² every 14 days until disease progression or participant intolerance
DRUGIrinotecan
180 mg/m² every 14 days until disease progression or participant intolerance
BIOLOGICALIMC-A12 (cixutumumab)
IMC-A12 10 mg/kg every 14 days until disease progression or participant intolerance
Sponsors
NSABP Foundation Inc
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) Rate at 18 Weeks | Approximately 18 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)] | Randomization up to 26.3 months |
| Overall Survival (OS) | Randomization up to 26.3 months |
| Progression Free Survival (PFS) Over Entire Duration | 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) | Randomization up to 26.3 months |
| Post-treatment Serum Levels of IMC-A12 in Participants Receiving IMC-A12 | 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 |
| Change in Behavioral and Health Outcomes [BAHO] Quality of Life (QoL) Questionnaire | Baseline, after Cycle 3 (14-day cycle), study discontinuation 30-day follow-up (up to 26.3 months) |
| Serum Anti-IMC-A12 Antibody Assessment | 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 |
| Toxicity of the Irinotecan + Cetuximab + IMC-A12 Regimen | Randomization up to 26.3 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Died During 30-Day Follow-Up | 26.3 months post-randomization up to 30-day post-treatment follow-up | Reported are the deaths during the 30-day follow-up period regardless of causality. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab + Irinotecan 500 mg/m² of Cetuximab administered by IV infusion then followed by 180 mg/m² of Irinotecan by IV infusion on Day 1 of each 14-day cycle until disease progression or participant intolerance. | 2 |
| Cetuximab + IMC-A12 + Irinotecan 500 mg/m² of Cetuximab administered by IV infusion then followed by 10 mg/kg of IMC-A12 IV followed by 180 mg/m² of Irinotecan by IV infusion on Day 1 of each 14-day cycle until disease progression or participant intolerance. | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Cetuximab + Irinotecan | Total | Cetuximab + IMC-A12 + Irinotecan |
|---|---|---|---|
| Age, Continuous | 52.0 years | 55.8 years | 59.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 1 / 2 |
Outcome results
Primary
Progression-Free Survival (PFS) Rate at 18 Weeks
Time frame: Approximately 18 Weeks
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
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)
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)]
Time frame: Randomization up to 26.3 months
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
Overall Survival (OS)
Time frame: Randomization up to 26.3 months
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
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
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
Progression Free Survival (PFS) Over Entire Duration
Time frame: Randomization up to 26.3 months
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
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
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
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
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Secondary
Toxicity of the Irinotecan + Cetuximab + IMC-A12 Regimen
Time frame: Randomization up to 26.3 months
Population: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.
Other Pre-specified
The Number of Participants Who Died During 30-Day Follow-Up
Reported are the deaths during the 30-day follow-up period regardless of causality.
Time frame: 26.3 months post-randomization up to 30-day post-treatment follow-up
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cetuximab + Irinotecan | The Number of Participants Who Died During 30-Day Follow-Up | 1 Participants |
| Cetuximab + IMC-A12 + Irinotecan | The Number of Participants Who Died During 30-Day Follow-Up | 1 Participants |