Back to resultsA Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before
Primary Purpose
Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Cisplatin
IMC-A12 (cixutumumab)
Cetuximab
IMC-A12 (cixutumumab)
Cetuximab
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Tumors, Antibodies, Monoclonal, Stage IIIb Metastatic Non-Small Cell Lung Cancer, Stage IV Metastatic Non-Small Cell Lung Cancer
Eligibility 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
Sites / Locations
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
- ImClone Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)
GCiC (Gemcitabine/Cisplatin/Cetuximab)
Arm Description
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)
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)
Outcomes
Primary Outcome Measures
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
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
Overall Survival (OS)
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.
Progression-Free Survival (PFS)
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.
Time To Progression (TTP)
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.
Duration of Response
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.
Number of Participants With Adverse Events (AEs) or Deaths
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.
Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity)
Maximum Concentration (Cmax) of Cixutumumab at Study Day 1
Cmax of Cixutumumab for Cycle 1
Cmax of Cixutumumab for Cycle 3
Cmax of Cixutumumab Cycle 5
Minimum Concentration (Cmin) of Cixutumumab at Study Day 1
Cmin of Cixutumumab for Cycle 1
Cmin of Cixutumumab for Cycle 3
Cmin of Cixutumumab for Cycle 5
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00870870
Brief Title
A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before
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 Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
Keywords
Tumors, Antibodies, Monoclonal, Stage IIIb Metastatic Non-Small Cell Lung Cancer, Stage IV Metastatic Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)
Arm Type
Experimental
Arm Description
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)
Arm Title
GCiC (Gemcitabine/Cisplatin/Cetuximab)
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
1000 milligrams per square meter (mg/m^2) on Days 1 and 8 of each cycle
[First 6 cycles (18 weeks)]
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
75 mg/m^2 on Day 1 of each cycle
[First 6 cycles (18 weeks)]
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
Cixutumumab, LY3012217
Intervention Description
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)]
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux®
Intervention Description
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)]
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
Cixutumumab, LY3012217
Intervention Description
10 mg/kg IV infusion, administered once every 2 weeks
(Maintenance therapy)
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux®
Intervention Description
500 mg/m^2 IV infusion, administered once every 2 weeks
(Maintenance therapy)
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Area under the curve (AUC) = 5, Day 1 of each cycle
[First 6 cycles (18 weeks)]
*Carboplatin will be replaced by Cisplatin
Primary Outcome Measure Information:
Title
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Description
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.
Time Frame
Randomization to measured progressive disease (PD) (up to 16.9 months)
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
Randomization to death due to any cause or censor (up to 30.4 months)
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
Randomization to PD or death due to any cause or censor (up to 16.9 months)
Title
Time To Progression (TTP)
Description
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.
Time Frame
Randomization to months until PD or censor (up to 16.9 months)
Title
Duration of Response
Description
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.
Time Frame
Date of first response to the date of PD or death due to any cause or censor ( up to 15.5 months)
Title
Number of Participants With Adverse Events (AEs) or Deaths
Description
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.
Time Frame
Randomization to last dose of study medication (up to 11.7 months) plus 30-day safety follow-up
Title
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
Title
Maximum Concentration (Cmax) of Cixutumumab at Study Day 1
Time Frame
Day 1
Title
Cmax of Cixutumumab for Cycle 1
Time Frame
Week 1 (Cycle 1, Day 1)
Title
Cmax of Cixutumumab for Cycle 3
Time Frame
Week 7 (Cycle 3, Day 1)
Title
Cmax of Cixutumumab Cycle 5
Time Frame
Week 13 (Cycle 5, Day 1)
Title
Minimum Concentration (Cmin) of Cixutumumab at Study Day 1
Time Frame
Day 1
Title
Cmin of Cixutumumab for Cycle 1
Time Frame
Week 1 (Cycle 1, Day 1)
Title
Cmin of Cixutumumab for Cycle 3
Time Frame
Week 7 (Cycle 3, Day 1)
Title
Cmin of Cixutumumab for Cycle 5
Time Frame
Week 13 (Cycle 5, Day 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
E-mail: ClinicalTrials@ ImClone.com
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
ImClone Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
ImClone Investigational Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
ImClone Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
ImClone Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30341
Country
United States
Facility Name
ImClone Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
ImClone Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
ImClone Investigational Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
ImClone Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45247
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before
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