Head and Neck Cancer
Conditions
Keywords
Squamous Cell Carcinoma in Head and Neck, Prior Platinum-based chemotherapy, Cetuximab, Erbitux, IMC-A12
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.
Interventions
BIOLOGICALIMC-A12 (cixutumumab)
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.
BIOLOGICALcetuximab (Erbitux ®)
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.
Sponsors
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline to measured PD (up to 27.66 months) | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With PFS at 6 Months | 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) | Baseline to date of death from any cause (up to 29.63 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. |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | Baseline to measured PD (up to 27.66 months) | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | Baseline through study completion (up to 29.63 months) | 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 | 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] | No data for biomarkers and serum antibodies were collected due to lack of an appropriate validated assay. |
| Duration of Response | Date of first response to the date of PD or death due to any cause (up to 23.98 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 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. |
Countries
United States
Participant flow
Pre-assignment details
Presented are the reasons the participants discontinued from the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| IMC-A12 (Cixutumumab) IMC-A12 (cixutumumab) 10 mg/kg dose administered as an IV infusion over a period of 1 hour once every 2 weeks. A cycle was defined as 4 weeks of therapy (4-week cycle). Treatment was continued until there was evidence of PD, unacceptable toxicity, or withdrawal of consent. | 47 |
| IMC-A12 (Cixutumumab) + Cetuximab IMC-A12 (cixutumumab) 10 mg/kg dose administered as an IV infusion over a period of 1 hour followed by cetuximab 500 mg/m\^2 dose administered as an IV infusion over a period of 2 hours; this sequence was repeated once every 2 weeks (4-week cycle). Treatment was continued until there was evidence of PD, unacceptable toxicity, or withdrawal of consent. | 44 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Found Ineligible After Randomization | 1 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrew Consent | 2 | 0 |
Baseline characteristics
| Characteristic | IMC-A12 (Cixutumumab) | Total | IMC-A12 (Cixutumumab) + Cetuximab |
|---|---|---|---|
| Age, Continuous | 60.0 years | 60.0 years | 59.0 years |
| Body Surface Area (BSA) | 1.80 square meters (m^2) STANDARD_DEVIATION 0.241 | 1.81 square meters (m^2) STANDARD_DEVIATION 0.254 | 1.82 square meters (m^2) STANDARD_DEVIATION 0.269 |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score 0 = Fully Active | 8 Participants | 16 Participants | 8 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score 1 = Ambulatory, Restricted Work Activity | 29 Participants | 57 Participants | 28 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score 2 = Ambulatory, No Work Activity | 10 Participants | 18 Participants | 8 Participants |
| Electrocardiogram (ECG) Abnormal | 27 Participants | 45 Participants | 18 Participants |
| Electrocardiogram (ECG) Normal | 20 Participants | 46 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 86 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 171.7 centimeters (cm) STANDARD_DEVIATION 10.53 | 172.5 centimeters (cm) STANDARD_DEVIATION 10.05 | 173.3 centimeters (cm) STANDARD_DEVIATION 9.56 |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 8 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 42 Participants | 76 Participants | 34 Participants |
| Region of Enrollment United States | 47 Participants | 91 Participants | 44 Participants |
| Sex: Female, Male Female | 11 Participants | 18 Participants | 7 Participants |
| Sex: Female, Male Male | 36 Participants | 73 Participants | 37 Participants |
| Weight | 70.5 kilograms (kg) STANDARD_DEVIATION 13.68 | 70.7 kilograms (kg) STANDARD_DEVIATION 15.93 | 70.9 kilograms (kg) STANDARD_DEVIATION 18.19 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 47 | 44 / 44 |
| serious Total, serious adverse events | 20 / 47 | 23 / 44 |
Outcome results
Primary
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.
Time frame: Baseline to measured PD (up to 27.66 months)
Population: Randomized participants who received at least 1 dose of study drug. Seven (7) participants in IMC-A12 (Cixutumumab) and 4 participants in IMC-A12 (Cixutumumab) + Cetuximab were censored for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMC-A12 (Cixutumumab) | Progression-Free Survival (PFS) | 1.9 months |
| IMC-A12 (Cixutumumab) + Cetuximab | Progression-Free Survival (PFS) | 2.0 months |
p-value: 0.0667Log Rank
Secondary
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.
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]
Population: No participants were analyzed due to lack of an appropriate validated assay.
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 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)
Population: Randomized participants who received at least 1 dose of study drug and had CR or PR. No participants were censored for duration of response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMC-A12 (Cixutumumab) | Duration of Response | 12.8 months |
| IMC-A12 (Cixutumumab) + Cetuximab | Duration of Response | 6.2 months |
Secondary
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.
Time frame: Baseline through study completion (up to 29.63 months)
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMC-A12 (Cixutumumab) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | TEAEs | 47 participants |
| IMC-A12 (Cixutumumab) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | Serious TEAEs | 20 participants |
| IMC-A12 (Cixutumumab) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | Death due to AEs | 2 participants |
| IMC-A12 (Cixutumumab) + Cetuximab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | TEAEs | 44 participants |
| IMC-A12 (Cixutumumab) + Cetuximab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | Serious TEAEs | 23 participants |
| IMC-A12 (Cixutumumab) + Cetuximab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | Death due to AEs | 6 participants |
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.
Time frame: Baseline to date of death from any cause (up to 29.63 months)
Population: Randomized participants who received at least 1 dose of study drug. Eleven (11) participants in IMC-A12 (Cixutumumab) group and 6 participants in IMC-A12 (Cixutumumab) + Cetuximab group were censored for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMC-A12 (Cixutumumab) | Overall Survival (OS) | 5.3 months |
| IMC-A12 (Cixutumumab) + Cetuximab | Overall Survival (OS) | 5.5 months |
p-value: 0.7455Log Rank
Secondary
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.
Time frame: Baseline to measured PD (up to 27.66 months)
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMC-A12 (Cixutumumab) | Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 2.1 percentage of participants |
| IMC-A12 (Cixutumumab) + Cetuximab | Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 9.1 percentage of participants |
p-value: 0.1935Fisher Exact
Secondary
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.
Time frame: 6 months
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMC-A12 (Cixutumumab) | Percentage of Participants With PFS at 6 Months | 4.3 percentage of participants |
| IMC-A12 (Cixutumumab) + Cetuximab | Percentage of Participants With PFS at 6 Months | 13.6 percentage of participants |