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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Pancreatic Cancer	Drug: Ixabepilone; Drug: Cetuximab	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	58 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II, Open Label Trial of Ixabepilone Plus Cetuximab as First Line Therapy for Metastatic Pancreatic Cancer
Study Start Date :	January 2007
Actual Primary Completion Date :	June 2009
Actual Study Completion Date :	June 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Ixabepilone plus Cetuximab; 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; Intravenous Infusion (IV), 32 mg/m^2 every 21 days.; Other Names: IXEMPRA®; Erbitux®; BMS-247550; BMS-564717 Drug: Cetuximab; 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.

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants Surviving at 6 Months [ Time Frame: From time of first dose of study drug through 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.

Secondary Outcome Measures :

1. Best Overall Tumor Response [ Time Frame: From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression) ]
   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.
2. Percentage of Participants With Objective Tumor Response [ Time Frame: 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 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.
3. Median Progression Free Survival Time [ Time Frame: From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression ]
   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.
4. Median Overall Survival Time [ Time Frame: From the first dosing date until death (last reported death was 21 months after first dose). ]
   Overall survival time was defined as the time in months from the first dosing date to the date of death.
5. Median Duration of Response [ Time Frame: 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). ]
   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.
6. Median Time to Response [ Time Frame: Time from first dose of study therapy until first date of PR or CR. Maximum time to response was 19 months. ]
   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.
7. 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) [ Time Frame: 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. ]
   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.
8. Number of Participants With Most Common Treatment-related Nonhematologic AE (>25%) By CTC v3 Grade (Gr) [ Time Frame: 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. ]
   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.
9. Number of Participants With Hematology, Liver Function, and Renal Laboratory Abnormalities By CTC v3 Grade (Gr) [ Time Frame: 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. ]
   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.
10. Number of Participants With Dose Reduction, Dose Delay, or Dose Interruption [ Time Frame: 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. ]
    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.
11. Percentage of Participants With Baseline Epidermal Growth Factor Receptor (EGFR) Tumor Expression [ Time Frame: Baseline ]
    EGFR expression was evaluated by means of an immunohistochemical assay using tumor tissue collected prior to receiving first dose.
12. Change From Baseline in FHSI-8 Total Score by Time-point [ Time Frame: 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) ]
    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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, District of Columbia
Georgetn Univ Lombardi Can Ctr
Washington, District of Columbia, United States, 20007
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
University Of Miami
Miami, Florida, United States, 33136
United States, Michigan
University Of Michigan
Ann Arbor, Michigan, United States, 48109
Wayne State University
Detroit, Michigan, United States, 48201
United States, Missouri
Ellis Fischel Cancer Center
Columbia, Missouri, United States, 65203
United States, South Carolina
Cancer Centers Of The Carolinas
Greenville, South Carolina, United States, 29615
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

R-Pharm

Investigators

Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

BMS Clinical Trials Disclosure 

Investigator Inquiry form 

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm 

Responsible Party:	R-Pharm
ClinicalTrials.gov Identifier:	NCT00383149 History of Changes
Other Study ID Numbers:	CA163-116
First Posted:	October 2, 2006
Results First Posted:	October 19, 2010
Last Update Posted:	March 10, 2016
Last Verified:	February 2016

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases	Cetuximab; Epothilones; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action