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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: Ixabepilone; Drug: Cetuximab

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / 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: BMS-247550; IXEMPRA®; Erbitux®; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: R-Pharm

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: September 28, 2006
• First Submitted That Met QC Criteria: September 28, 2006
• First Posted (Estimate): October 2, 2006

Study Record Updates

• Last Update Posted (Estimate): March 10, 2016
• Last Update Submitted That Met QC Criteria: February 9, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: CA163-116