Study of IMC-A12, Alone or in Combination With Cetuximab, in Participants With Recurrent or Metastatic Squamous Cell Carcinoma (MSCC) of the Head and Neck
Primary Purpose
Head and Neck Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IMC-A12 (cixutumumab)
cetuximab (Erbitux ®)
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring Squamous Cell Carcinoma in Head and Neck, Prior Platinum-based chemotherapy, Cetuximab, Erbitux, IMC-A12
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically-confirmed squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity, metastasis or recurrence documented by clinical imaging studies
- Measurable disease, lesion size ≥ 2 centimeters (cm) on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
- Clinical documentation of disease progression during treatment with or within 90 days after receiving the last cycle of platinum-based chemotherapy (with or without radiation therapy)
- If prior treatment with anti-epidermal growth factor receptor (EGFR) therapy, the time to recurrence from last exposure to anti-EGFR therapy is > 90 days
- Adequate hematologic function
- Adequate hepatic function
- Adequate coagulation function or is on a stable dose of an anticoagulant.
- Adequate renal function
- Fasting serum glucose <120 milligrams per deciliter (mg/dL) or below the upper limit of normal (ULN)
- Women of childbearing potential and men 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:
- Not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, must have recovered to grade ≤ 2
- Is receiving any other investigational agent(s)
- History of treatment with other agents targeting the insulin-like growth factor receptor (IGFR)
- Is receiving concurrent treatment with other anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
- History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12
- 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 < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
- Pregnant or breastfeeding
- Is receiving therapy with immunosuppressive agents
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
- ImClone Investigational Site
- ImClone Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
IMC-A12 (cixutumumab)
IMC-A12 (cixutumumab) + cetuximab
Arm Description
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
PFS was defined as the interval from randomization until PD or death, whichever occurred first. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.0) criteria. PD was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death.
Secondary 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 RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants is calculated as a total number of participants with CR or PR divided by the total number of participants treated then multiplied by 100.
Percentage of Participants With PFS at 6 Months
PFS at 6 months was defined as the percentage of participants who have neither experienced PD nor died at 6 months after the date of randomization. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. Percentage of participants is calculated as the total number of participants with PFS at 6 months divided by the total number of participants treated then multiplied by 100.
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.
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 PD or death. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter 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 PD.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths
TEAEs were defined as serious and other non-serious adverse events (AEs) that occurred or worsened after study treatment (regardless of causality). Data presented are the number of participants who experienced TEAEs including serious TEAEs, and deaths during the study including the 30-day follow-up. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events section of this report.
Blood And Tissue Biomarkers And Development of Serum Antibodies Against IMC-A12 and Cetuximab
No data for biomarkers and serum antibodies were collected due to lack of an appropriate validated assay.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00617734
Brief Title
Study of IMC-A12, Alone or in Combination With Cetuximab, in Participants With Recurrent or Metastatic Squamous Cell Carcinoma (MSCC) of the Head and Neck
Official Title
A Randomized Phase 2 Open-Label Study of IMC-A12, as a Single Agent or in Combination With Cetuximab, in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Disease Progression on Prior Platinum-Based Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
July 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 if IMC-A12 alone or in combination with Cetuximab (Erbitux®) can increase the time prior to disease progression in participants with Squamous Cell Head and Neck Cancer who have had disease progression and platinum-containing chemotherapeutic regimen.
Detailed Description
The routine cancer treatments for Squamous Cell Carcinoma Head and Neck Cancer have improved but still leave a percentage of participants with incurable disease. New alternatives for participants whose disease is refractory to existing therapies is needed.
IMC-A12 is a monoclonal antibody which binds to special receptors known as insulin-like growth factor-I receptor (IGF-IR). This binding action has been shown to inhibit the growth of a variety of human tumor cell lines.
The purpose of this study is to evaluate the effects of IMC-A12 by itself or with Cetuximab (Erbitux®) in participants with Squamous Cell Carcinoma Head and Neck Cancer that has spread to other parts of the body, and to determine how long the drug remains in the body. The study will also look at what side effects IMC-A12 may cause when a participant is receiving treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Squamous Cell Carcinoma in Head and Neck, Prior Platinum-based chemotherapy, Cetuximab, Erbitux, IMC-A12
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
97 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IMC-A12 (cixutumumab)
Arm Type
Experimental
Arm Title
IMC-A12 (cixutumumab) + cetuximab
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
IMC-A12 (cixutumumab)
Other Intervention Name(s)
Cixutumumab, LY3012217
Intervention Description
IMC-A12 10 milligrams per kilogram (mg/kg) over one hour every two weeks. A cycle is defined as four weeks of therapy. Participants will continue on study until evidence of progressive disease, or unacceptable toxicity develops.
Intervention Type
Biological
Intervention Name(s)
cetuximab (Erbitux ®)
Other Intervention Name(s)
Erbitux®
Intervention Description
IMC-A12 10 mg/kg over one hour followed by cetuximab 500 milligrams per square meter (mg/m^2) over two hours. This sequence will be repeated every two weeks. Participants will continue on study until evidence of progressive disease or unacceptable toxicity develops.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS was defined as the interval from randomization until PD or death, whichever occurred first. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.0) criteria. PD was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death.
Time Frame
Baseline to measured PD (up to 27.66 months)
Secondary 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 RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants is calculated as a total number of participants with CR or PR divided by the total number of participants treated then multiplied by 100.
Time Frame
Baseline to measured PD (up to 27.66 months)
Title
Percentage of Participants With PFS at 6 Months
Description
PFS at 6 months was defined as the percentage of participants who have neither experienced PD nor died at 6 months after the date of randomization. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. Percentage of participants is calculated as the total number of participants with PFS at 6 months divided by the total number of participants treated then multiplied by 100.
Time Frame
6 months
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
Baseline to date of death from any cause (up to 29.63 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 PD or death. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter 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 PD.
Time Frame
Date of first response to the date of PD or death due to any cause (up to 23.98 months)
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths
Description
TEAEs were defined as serious and other non-serious adverse events (AEs) that occurred or worsened after study treatment (regardless of causality). Data presented are the number of participants who experienced TEAEs including serious TEAEs, and deaths during the study including the 30-day follow-up. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events section of this report.
Time Frame
Baseline through study completion (up to 29.63 months)
Title
Blood And Tissue Biomarkers And Development of Serum Antibodies Against IMC-A12 and Cetuximab
Description
No data for biomarkers and serum antibodies were collected due to lack of an appropriate validated assay.
Time Frame
Biomarkers [pre-dose, Cycle 1 (Day 15), (Cycle 2 (Day 1), and end of treatment]; Immunogenicity [pre-dose, prior to first infusion for Cycle 3, Cycle 5, and 30-day safety follow-up]
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically-confirmed squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity, metastasis or recurrence documented by clinical imaging studies
Measurable disease, lesion size ≥ 2 centimeters (cm) on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
Clinical documentation of disease progression during treatment with or within 90 days after receiving the last cycle of platinum-based chemotherapy (with or without radiation therapy)
If prior treatment with anti-epidermal growth factor receptor (EGFR) therapy, the time to recurrence from last exposure to anti-EGFR therapy is > 90 days
Adequate hematologic function
Adequate hepatic function
Adequate coagulation function or is on a stable dose of an anticoagulant.
Adequate renal function
Fasting serum glucose <120 milligrams per deciliter (mg/dL) or below the upper limit of normal (ULN)
Women of childbearing potential and men 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:
Not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, must have recovered to grade ≤ 2
Is receiving any other investigational agent(s)
History of treatment with other agents targeting the insulin-like growth factor receptor (IGFR)
Is receiving concurrent treatment with other anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12
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 < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
Pregnant or breastfeeding
Is receiving therapy with immunosuppressive agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
ImClone Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
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
30322
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
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
ImClone Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
ImClone Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
ImClone Investigational Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
ImClone Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
ImClone Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
ImClone Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
ImClone Investigational Site
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of IMC-A12, Alone or in Combination With Cetuximab, in Participants With Recurrent or Metastatic Squamous Cell Carcinoma (MSCC) of the Head and Neck
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