A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before

• ClinicalTrials.gov Identifier: NCT00870870
• Recruitment Status: Completed
• First Posted: March 27, 2009
• Results First Posted: June 1, 2018
• Last Update Posted: June 1, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purpose of this study is to determine the number of participants whose cancer shrinks or disappears after treatment on the study.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Gemcitabine; Drug: Cisplatin; Biological: IMC-A12 (cixutumumab); Biological: Cetuximab; Drug: Carboplatin	Phase 2

Detailed Description:

Participants with Stage IIIb or IV non-small cell lung cancer (NSCLC) who have not received previous chemotherapy will be stratified, based on disease histology (squamous versus [vs.] nonsquamous).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Open Label, Stratified Phase 2 Trial of Gemcitabine, Carboplatin, and Cetuximab With Vs. Without IMC-A12 in Chemotherapy-Naive Patients With Advanced/Metastatic Non-Small Cell Lung Cancer
• Study Start Date: March 2009
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: May 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab); Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met *Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)	Drug: Gemcitabine; 1000 milligrams per square meter (mg/m^2) on Days 1 and 8 of each cycle [First 6 cycles (18 weeks)]; Drug: Cisplatin; 75 mg/m^2 on Day 1 of each cycle [First 6 cycles (18 weeks)]; Biological: IMC-A12 (cixutumumab); 6 milligrams per kilogram (mg/kg) intravenous (IV) infusion, administered once per week (on Days 1, 8, and 15 of each cycle) [First 6 cycles (18 weeks)]; Other Names: Cixutumumab; LY3012217; Biological: Cetuximab; 400 mg/m^2 IV infusion, administered on Day 1 of Cycle 1, 250 mg/m^2 once per week thereafter [First 6 cycles (18 weeks)]; Other Name: Erbitux®; Biological: IMC-A12 (cixutumumab); 10 mg/kg IV infusion, administered once every 2 weeks (Maintenance therapy); Other Names: Cixutumumab; LY3012217; Biological: Cetuximab; 500 mg/m^2 IV infusion, administered once every 2 weeks (Maintenance therapy); Other Name: Erbitux®; Drug: Carboplatin; Area under the curve (AUC) = 5, Day 1 of each cycle [First 6 cycles (18 weeks)] *Carboplatin will be replaced by Cisplatin
Active Comparator: GCiC (Gemcitabine/Cisplatin/Cetuximab); Cycles repeat every 3 weeks for 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met *Cisplatin will replace Carboplatin. GCC plus cixutumumab will change to GCiC plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)	Drug: Gemcitabine; 1000 milligrams per square meter (mg/m^2) on Days 1 and 8 of each cycle [First 6 cycles (18 weeks)]; Drug: Cisplatin; 75 mg/m^2 on Day 1 of each cycle [First 6 cycles (18 weeks)]; Biological: Cetuximab; 400 mg/m^2 IV infusion, administered on Day 1 of Cycle 1, 250 mg/m^2 once per week thereafter [First 6 cycles (18 weeks)]; Other Name: Erbitux®; Biological: Cetuximab; 500 mg/m^2 IV infusion, administered once every 2 weeks (Maintenance therapy); Other Name: Erbitux®; Drug: Carboplatin; Area under the curve (AUC) = 5, Day 1 of each cycle [First 6 cycles (18 weeks)] *Carboplatin will be replaced by Cisplatin

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [ Time Frame: Randomization to measured progressive disease (PD) (up to 16.9 months) ]
   ORR was defined as the percentage of participants achieving either CR or PR. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions and the normalization of the tumour marker level. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Percentage of participants is calculated as a total number of participants with CR or PR / total number of participants treated * 100.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Randomization to death due to any cause or censor (up to 30.4 months) ]
   OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact.
2. Progression-Free Survival (PFS) [ Time Frame: Randomization to PD or death due to any cause or censor (up to 16.9 months) ]
   PFS was defined as the duration from the date of randomization until disease progression or death due to any cause, whichever occurred first. Response was defined using RECIST, v 1.0 criteria. PD was defined as having a ≥20% increase in sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants who were alive and without disease progression, PFS was censored at the date of last objective tumor assessment. For participants who did not experience disease progression and were lost to follow-up, PFS was censored at the date of the last objective tumor assessment or the date of last contact.
3. Time To Progression (TTP) [ Time Frame: Randomization to months until PD or censor (up to 16.9 months) ]
   TTP was defined as the duration from the date of randomization until the date of disease progression. Response was defined using RECIST v 1.0 criteria. PD was defined as having a ≥20% increase in the sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants without disease progression, TTP was censored at the date of last objective tumor assessment. For participants without disease progression and were subsequently lost to follow-up, TTP was censored at the date of last follow-up visit or at the date of last contact.
4. Duration of Response [ Time Frame: Date of first response to the date of PD or death due to any cause or censor ( up to 15.5 months) ]
   The duration of CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of disease progression or death. Response was defined using RECIST v 1.0 criteria. CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as having at least a 30% decrease in sum of LD of target lesions. Duration of response was censored on the date of last tumor assessment for participants who were alive and have no evidence of disease progression.
5. Number of Participants With Adverse Events (AEs) or Deaths [ Time Frame: Randomization to last dose of study medication (up to 11.7 months) plus 30-day safety follow-up ]
   Data presented are the number of participants who experienced 1 or more AEs, serious AEs (SAEs), and AEs that lead to death during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this report.
6. Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity) [ Time Frame: Prior to first infusions of Cycles 1, 3, and 5 and 30 days following the end of therapy ]
7. Maximum Concentration (Cmax) of Cixutumumab at Study Day 1 [ Time Frame: Day 1 ]
8. Cmax of Cixutumumab for Cycle 1 [ Time Frame: Week 1 (Cycle 1, Day 1) ]
9. Cmax of Cixutumumab for Cycle 3 [ Time Frame: Week 7 (Cycle 3, Day 1) ]
10. Cmax of Cixutumumab Cycle 5 [ Time Frame: Week 13 (Cycle 5, Day 1) ]
11. Minimum Concentration (Cmin) of Cixutumumab at Study Day 1 [ Time Frame: Day 1 ]
12. Cmin of Cixutumumab for Cycle 1 [ Time Frame: Week 1 (Cycle 1, Day 1) ]
13. Cmin of Cixutumumab for Cycle 3 [ Time Frame: Week 7 (Cycle 3, Day 1) ]
14. Cmin of Cixutumumab for Cycle 5 [ Time Frame: Week 13 (Cycle 5, Day 1) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Has histologically or cytologically confirmed, Stage IIIb - IV NSCLC
• Has metastatic disease
• Has a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)
• Has adequate hematologic function
• Has adequate hepatic function
• Has adequate renal function
• Women of childbearing potential 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

Exclusion Criteria:

• Has uncontrolled brain metastases
• Has leptomeningeal disease
• Has received previous chemotherapy for NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization)
• Receiving any other investigational agent(s)
• Has a history of treatment with other agents targeting the insulin-like growth factor (IGF) or the epidermal growth factor (EGF) receptor
• Has a known allergy / history of hypersensitivity reaction to any of the treatment components
• 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 <160 milligrams per deciliter (mg/dL) or below the upper limit of normal (ULN) and hemoglobin A1C≤ 7%] and that they are on a stable dietary or therapeutic regimen for this condition
• Has an uncontrolled intercurrent illness
• Pregnant or lactating
• 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 treated with curative intent and no known active disease present and no treatment administered during the last 3 years
• Has superior vena cava syndrome contraindicating hydration
• Has current clinically-relevant coronary artery disease (New York Heart Association III or IV) or uncontrolled congestive heart failure
• Has any National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version (v) 3.0 Grade ≥2 peripheral neuropathy
• Has significant third space fluid retention, requiring repeated drainage

Contacts and Locations

Locations

United States, Alabama

ImClone Investigational Site

Anniston, Alabama, United States, 36207

United States, California

ImClone Investigational Site

La Jolla, California, United States, 92093

ImClone Investigational Site

Orange, California, United States, 92868

United States, Florida

ImClone Investigational Site

Orlando, Florida, United States, 32806

United States, Georgia

ImClone Investigational Site

Atlanta, Georgia, United States, 30341

United States, Illinois

ImClone Investigational Site

Chicago, Illinois, United States, 60612

ImClone Investigational Site

Chicago, Illinois, United States, 60637

United States, New Mexico

ImClone Investigational Site

Albuquerque, New Mexico, United States, 87131

United States, New York

ImClone Investigational Site

New York, New York, United States, 10011

ImClone Investigational Site

New York, New York, United States, 10021

ImClone Investigational Site

New York, New York, United States, 10032

United States, Ohio

ImClone Investigational Site

Cincinnati, Ohio, United States, 45247

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: E-mail: ClinicalTrials@ ImClone.com; Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00870870
• Other Study ID Numbers: 13930; CP02-0860 ( Other Identifier: CDER ); CP13-0811 ( Other Identifier: ImClone, LLC ); I5A-IE-JAEF ( Other Identifier: Eli Lilly and Company )
• First Posted: March 27, 2009
• Results First Posted: June 1, 2018
• Last Update Posted: June 1, 2018
• Last Verified: May 2018

Keywords provided by Eli Lilly and Company:

Tumors; Antibodies, Monoclonal; Stage IIIb Metastatic Non-Small Cell Lung Cancer; Stage IV Metastatic Non-Small Cell Lung Cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gemcitabine; Carboplatin; Cetuximab; Antibodies, Monoclonal; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological