A Phase II, Trial of Ixabepilone Plus Cetuximab as First Line Therapy for Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this clinical research study is to learn if ixabepilone plus cetuximab improves survival when given as 1st line chemotherapy in subjects with metastatic pancreatic cancer compared to historical data. The safety of this combination treatment will also be studied.

Official Title
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A Phase II, Open Label Trial of Ixabepilone Plus Cetuximab as First Line Therapy for Metastatic Pancreatic Cancer

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: Ixabepilone
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of pancreatic adenocarcinoma (locally advanced disease that is not surgically resectable, or distant metastatic disease) Participants must have measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines Participants must not have received prior chemotherapy, immunotherapy or chemoradiotherapy for advanced pancreas cancer Karnofsky performance status (KPS) of 70-100 Adequate hematologic, hepatic and renal function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ixabepilone plus Cetuximab<br>All participants were administered ixabepilone at a starting dose of 32 mg/m^2 as a 3-hour intravenous (IV) infusion every 3 weeks. In addition, all participants were administered an initial dose of cetuximab (400 mg/m^2 IV over 2 hours) followed by a weekly lower dose (250 mg/m^2 IV over 1 hour). | Drug: Ixabepilone<br>* Intravenous Infusion (IV), 32 mg/m^2 every 21 days.<br>* Other names: BMS-564717;Drug: Cetuximab<br>* Initial dose of 400 mg/m^2 intravenous (IV) over 2 hours) followed by a weekly lower dose of 250 mg/m^2 IV over 1 hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Surviving at 6 Months | The percentage of participants surviving at 6 months was defined as the number of treated participants who had not died prior to 6 months from the date of their first dose divided by the total number of treated participants. | From time of first dose of study drug through 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Tumor Response | Tumor response was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)= disappearance of all non-target lesions, Partial Response (PR)= at least 30% reduction in the sum of the longest diameter (LD) of all target lesions in reference to the baseline sum LD; Stable Disease (SD)= neither PR nor progressive disease (PD) criteria were met; PD = at least 20% increase in the sum of the LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline. | From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression) | 
| Percentage of Participants With Objective Tumor Response | Percentage of participants with objective tumor response was determined by the number of participants with PR or CR divided by the total number of response-evaluable participants. Tumor response was assessed according RECIST criteria: PR=at least 30% reduction in the sum of the LD of all target lesions in reference to the baseline sum LD, CR=Disappearance of all non-target lesions. | From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression | 
| Median Progression Free Survival Time | Progression-Free Survival (PFS) time was defined as the time, in months, from the first dosing date until the date of disease progression or death from any cause. | From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression | 
| Median Overall Survival Time | Overall survival time was defined as the time in months from the first dosing date to the date of death. | From the first dosing date until death (last reported death was 21 months after first dose). | 
| Median Duration of Response | Duration of response was defined as the number of months from when measurement criteria were first met for CR or PR (whichever was recorded first) until the first date of disease progression or death. Complete Response (CR)= disappearance of all non-target lesions, Partial Response (PR)= at least 30% reduction in the sum of the longest diameter (LD) of all target lesions in reference to the baseline sum LD. | From first date recorded for CR or PR until the first date of disease progression or death (last participant with tumor response progressed 6.5 months after documented response). | 
| Median Time to Response | Time to response was defined as the number of weeks from first dose of study therapy (ixabepilone or cetuximab) until measurement criteria were first met for PR or CR, whichever status was recorded first. Complete Response (CR)= disappearance of all non-target lesions, Partial Response (PR)= at least 30% reduction in the sum of the longest diameter (LD) of all target lesions in reference to the baseline sum LD. | Time from first dose of study therapy until first date of PR or CR. Maximum time to response was 19 months. | 
| Number of Participants With Death Within 30 Days of Last Dose, Any Serious Adverse Event (SAE), Any Adverse Event (AE) Leading to Discontinuation (DC), or Any Treatment-related AEs By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr) | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event. | From the time of first dose of study drug to ≤30 days after the end of the last dose of study drug or until resolution of study drug-related toxicity. | 
| Number of Participants With Most Common Treatment-related Nonhematologic AE (>25%) By CTC v3 Grade (Gr) | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. Acneform rash and peripheral neuropathy were captured by multiple MedDRA preferred terms. Acneform rash included rash, rash pustular, and rash pruritic preferred terms. Peripheral neuropathy included neuromuscular toxicity, peripheral motor neuropathy, and peripheral sensorimotor neuropathy preferred terms. | From the time of first dose of study drug to ≤30 days after the end of the last dose of study drug or until resolution of study drug-related toxicity. | 
| Number of Participants With Hematology, Liver Function, and Renal Laboratory Abnormalities By CTC v3 Grade (Gr) | Laboratory results were graded according to CTC v 3.0. Hematology laboratory evaluations included absolute neutrophil count (ANC), white blood cell count (WBC), platelets (PLT), and hemoglobin (HGB). Liver function laboratory evaluations included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin. Renal function laboratory evaluation included creatinine. | From the time of first dose of study drug to ≤30 days after the end of the last dose of study drug or until resolution of study drug-related toxicity. | 
| Number of Participants With Dose Reduction, Dose Delay, or Dose Interruption | Dose reduction of ixabepilone and/or cetuximab due to toxicity was permitted for participants deriving benefit from therapy. Each drug could be dose modified independently of the others. Participants unable to start a cycle due to unacceptable toxicity related to ixabepilone or cetuximab could have therapy delayed for up to 4 weeks. If toxicities prevented the administration of ixabepilone or cetuximab therapy, participants continued receiving the other therapy as scheduled. A dose interruption for ixabepilone or cetuximab was defined as any interruption during the infusion period. | From the first dosing date of Cycle 1 until the last dosing date of the last cycle. Last dosing cycle for a participant was Cycle 21. | 
| Percentage of Participants With Baseline Epidermal Growth Factor Receptor (EGFR) Tumor Expression | EGFR expression was evaluated by means of an immunohistochemical assay using tumor tissue collected prior to receiving first dose. | Baseline | 
| Change From Baseline in FHSI-8 Total Score by Time-point | The FHSI-8 includes eight items representing pancreatic-related symptoms; each symptom is rated by participants on a scale of from 0 to 4. The FHSI-8 total score ranges in value from 0 to 32, with higher scores representing fewer symptoms and lower scores representing more symptoms. Scoring of the FHSI-8 was to be conducted according to the Functional Assessment of Chronic Illness Therapy (FACIT) manual. The symptom assessment was to include treated participants who had baseline measurement and at least one on-study measurement of FHSI-8 questionnaire. | Baseline, Week 3, Week 6, Week 9, Week 12, Week 12, Week 18, Week 24 and every 3 weeks through end of study (participant death/withdrawal from study) |