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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00870870
• Other study ID #: 13930
• Secondary ID: CP02-0860CP13-08
• Status: Completed
• Phase: Phase 2
• Start date: March 2009
• Est. completion date: May 2012

Study information

• Verified date: May 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: May 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Gemcitabine
1000 milligrams per square meter (mg/m^2) on Days 1 and 8 of each cycle [First 6 cycles (18 weeks)]
• 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)]
• 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)]
• IMC-A12 (cixutumumab)
10 mg/kg IV infusion, administered once every 2 weeks (Maintenance therapy)
• Cetuximab
500 mg/m^2 IV infusion, administered once every 2 weeks (Maintenance therapy)

Drug:
• Carboplatin
Area under the curve (AUC) = 5, Day 1 of each cycle [First 6 cycles (18 weeks)] *Carboplatin will be replaced by Cisplatin

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Albuquerque	New Mexico
United States	ImClone Investigational Site	Anniston	Alabama
United States	ImClone Investigational Site	Atlanta	Georgia
United States	ImClone Investigational Site	Chicago	Illinois
United States	ImClone Investigational Site	Chicago	Illinois
United States	ImClone Investigational Site	Cincinnati	Ohio
United States	ImClone Investigational Site	La Jolla	California
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	Orange	California
United States	ImClone Investigational Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Randomization to measured progressive disease (PD) (up to 16.9 months)
Secondary	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.	Randomization to death due to any cause or censor (up to 30.4 months)
Secondary	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.	Randomization to PD or death due to any cause or censor (up to 16.9 months)
Secondary	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.	Randomization to months until PD or censor (up to 16.9 months)
Secondary	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.	Date of first response to the date of PD or death due to any cause or censor ( up to 15.5 months)
Secondary	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.	Randomization to last dose of study medication (up to 11.7 months) plus 30-day safety follow-up
Secondary	Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity)		Prior to first infusions of Cycles 1, 3, and 5 and 30 days following the end of therapy
Secondary	Maximum Concentration (Cmax) of Cixutumumab at Study Day 1		Day 1
Secondary	Cmax of Cixutumumab for Cycle 1		Week 1 (Cycle 1, Day 1)
Secondary	Cmax of Cixutumumab for Cycle 3		Week 7 (Cycle 3, Day 1)
Secondary	Cmax of Cixutumumab Cycle 5		Week 13 (Cycle 5, Day 1)
Secondary	Minimum Concentration (Cmin) of Cixutumumab at Study Day 1		Day 1
Secondary	Cmin of Cixutumumab for Cycle 1		Week 1 (Cycle 1, Day 1)
Secondary	Cmin of Cixutumumab for Cycle 3		Week 7 (Cycle 3, Day 1)
Secondary	Cmin of Cixutumumab for Cycle 5		Week 13 (Cycle 5, Day 1)