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

• Sponsor: R-Pharm (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00383149
• Collaborator: (none)
• Enrollment: 58
• Locations: 9
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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

• Study Type: Interventional
• 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: Jan 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

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

Primary Outcome Measures

1. Percentage of Participants Surviving at 6 Months [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 [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 [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 [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 [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 [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 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) [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) [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) [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Georgetn Univ Lombardi Can Ctr	Washington	District of Columbia	United States	20007
2	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
3	University Of Miami	Miami	Florida	United States	33136
4	University Of Michigan	Ann Arbor	Michigan	United States	48109
5	Wayne State University	Detroit	Michigan	United States	48201
6	Ellis Fischel Cancer Center	Columbia	Missouri	United States	65203
7	Cancer Centers Of The Carolinas	Greenville	South Carolina	United States	29615
8	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
9	West Virginia University	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

• R-Pharm

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: R-Pharm
• ClinicalTrials.gov Identifier: NCT00383149
• Other Study ID Numbers: CA163-116
• First Posted: Oct 2, 2006
• Last Update Posted: Mar 10, 2016
• Last Verified: Feb 1, 2016

• Additional relevant MeSH terms: Pancreatic Neoplasms; Cetuximab

Study Results

Participant Flow

Pre-assignment Detail	Of the 58 participants enrolled, 4 were never treated.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Period Title: Overall Study
STARTED	54
COMPLETED	0
NOT COMPLETED	54

Baseline Characteristics

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Overall Participants	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.0
Age, Customized (participants) [Number]
Age Greater than, equal to 65 years	22 40.7%
Age less than 65 years	32 59.3%
Sex: Female, Male (Count of Participants)
Female	19 35.2%
Male	35 64.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Surviving at 6 Months
Description	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.
Time Frame	From time of first dose of study drug through 6 months

Outcome Measure Data

Analysis Population Description

Treated participants; all participants who received at least one dose of ixabepilone or cetuximab. Participants who did not die prior to 6 months but dropped out of the study were not included in the numerator.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	54
Number (95% Confidence Interval) [percentage of participants]	57.4 106.3%

2. Secondary Outcome

Title	Best Overall Tumor Response
Description	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.
Time Frame	From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression)

Outcome Measure Data

Analysis Population Description

Response-evaluable participants; all participants with measurable disease who received at least one dose of ixabepilone or cetuximab and who had at least one on-treatment tumor assessment.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	31
Participants with Complete Response	0 0%
Participants with Partial Response	4 7.4%
Participants with Stable Disease	24 44.4%
Participants with Progressive Disease	2 3.7%
Participants with Response Unable to be Determined	1 1.9%

3. Secondary Outcome

Title	Percentage of Participants With Objective Tumor Response
Description	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.
Time Frame	From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression

Outcome Measure Data

Analysis Population Description

Response-evaluable participants; all participants with measurable disease who received at least one dose of ixabepilone or cetuximab and who had at least one on-treatment tumor assessment.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	31
Number (95% Confidence Interval) [percentage of participants]	12.9 23.9%

4. Secondary Outcome

Title	Median Progression Free Survival Time
Description	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.
Time Frame	From time of first dose of study until 16.49 months (longest period for participant between first dose and documented disease progression

Outcome Measure Data

Analysis Population Description

Treated participants; all participants who received at least one dose of ixabepilone or cetuximab. Participants without disease progression or death were censored at the last tumor assessment.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	54
Median (95% Confidence Interval) [months]	3.9

5. Secondary Outcome

Title	Median Overall Survival Time
Description	Overall survival time was defined as the time in months from the first dosing date to the date of death.
Time Frame	From the first dosing date until death (last reported death was 21 months after first dose).

Outcome Measure Data

Analysis Population Description

Treated participants; all participants who received at least one dose of ixabepilone or cetuximab. Participants without a reported date of death were censored at the last known alive date.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	54
Median (95% Confidence Interval) [months]	7.6

6. Secondary Outcome

Title	Median Duration of Response
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Response-evaluable participants whose best response was PR or CR. Participants without disease progression or death were censored at the last tumor assessment date.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	4
Median (95% Confidence Interval) [months]	5.7

7. Secondary Outcome

Title	Median Time to Response
Description	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 Frame	Time from first dose of study therapy until first date of PR or CR. Maximum time to response was 19 months.

Outcome Measure Data

Analysis Population Description

Response-evaluable participants whose best response was PR or CR.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	4
Median (Full Range) [weeks]	8.8

8. Secondary Outcome

Title	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)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Treated participants; all participants who received at least one dose of ixabepilone or cetuximab. The 53 participants reporting treatment-related AEs included 1 additional participant who also developed Grade 5 viscous intestinal perforation, which was also captured under death within 30 days of last dose category.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	54
All deaths within 30 days of last dose	7 13%
Any SAE	32 59.3%
Gr 2 (moderate) AE leading to DC	2 3.7%
Gr 3 (severe) AE leading to DC	9 16.7%
Gr 4 (life-threatening) AE leading to DC	3 5.6%
All AEs leading to DC	14 25.9%
Gr 1 (mild) treatment-related AE	4 7.4%
Gr 2 (moderate) treatment-related AE	13 24.1%
Gr 3 (severe) treatment-related AE	25 46.3%
Gr 4 (life-threatening) treatment-related AE	10 18.5%
Gr 5 (death) treatment-related AE	1 1.9%
All treatment-related AEs	53 98.1%

9. Secondary Outcome

Title	Number of Participants With Most Common Treatment-related Nonhematologic AE (>25%) By CTC v3 Grade (Gr)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Treated participants; all participants who received at least one dose of ixabepilone or cetuximab.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	54
Gr 1 (mild) acneform rash	21 38.9%
Gr 2 (moderate) acneform rash	13 24.1%
Gr 3 (severe) acneform rash	1 1.9%
All acneform rash	35 64.8%
Gr 1 (mild) fatigue	8 14.8%
Gr 2 (moderate) fatigue	13 24.1%
Gr 3 (severe) fatigue	8 14.8%
Gr 4 (life-threatening) fatigue	1 1.9%
All fatigue	30 55.6%
Gr 1 (mild) alopecia	13 24.1%
Gr 2 (moderate) alopecia	12 22.2%
All alopecia	25 46.3%
Gr 1 (mild) nausea	13 24.1%
Gr 2 (moderate) nausea	6 11.1%
Gr 3 (severe) nausea	3 5.6%
All nausea	22 40.7%
Gr 1 (mild) diarrhea	11 20.4%
Gr 2 (moderate) diarrhea	4 7.4%
Gr 3 (severe) diarrhea	1 1.9%
Gr 4 (life-threatening) diarrhea	2 3.7%
All diarrhea	18 33.3%
Gr 1 (mild) vomiting	12 22.2%
Gr 2 (moderate) vomiting	2 3.7%
Gr 3 (severe) vomiting	3 5.6%
All vomiting	17 31.5%
Gr 1 (mild) peripheral neuropathy	12 22.2%
Gr 2 (moderate) peripheral neuropathy	1 1.9%
Gr 3 (severe) peripheral neuropathy	3 5.6%
All peripheral neuropathy	16 29.6%
Gr 1 (mild) hypomagnesemia	7 13%
Gr 2 (moderate) hypomagnesemia	4 7.4%
Gr 3 (severe) hypomagnesemia	1 1.9%
Gr 4 (life-threatening) hypomagnesemia	3 5.6%
All hypomagnesemia	15 27.8%

10. Secondary Outcome

Title	Number of Participants With Hematology, Liver Function, and Renal Laboratory Abnormalities By CTC v3 Grade (Gr)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Treated participants; all participants who received at least one dose of ixabepilone or cetuximab. n= number of participants with laboratory data available

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	54
Gr 0 (no abnormality) WBC, n=51	12 22.2%
Gr 1 (mild) WBC, n=51	9 16.7%
Gr 2 (moderate) WBC, n=51	9 16.7%
Gr 3 (severe) WBC, n=51	17 31.5%
Gr 4 (life-threatening) WBC, n=51	4 7.4%
Gr 1-4 WBC, n=51	39 72.2%
Gr 3-4 WBC, n=51	21 38.9%
Gr 0 (no abnormality) ANC, n=50	12 22.2%
Gr 1 (mild) ANC, n=50	8 14.8%
Gr 2 (moderate) ANC, n=50	12 22.2%
Gr 3 (severe) ANC, n=50	10 18.5%
Gr 4 (life-threatening) ANC, n=50	8 14.8%
Gr 1-4 ANC, n=50	38 70.4%
Gr 3-4 ANC, n=51	18 33.3%
Gr 0 (no abnormality) platelet count, n=51	29 53.7%
Gr 1 (mild) platelet count, n=51	18 33.3%
Gr 2 (moderate) platelet count, n=51	4 7.4%
Gr 1-4 platelet count, n=51	2 3.7%
Gr 0 (no abnormality) HGB, n=51	3 5.6%
Gr 1 (mild) HGB, n=51	28 51.9%
Gr 2 (moderate) HGB, n=51	18 33.3%
Gr 3 (severe) HGB, n=51	2 3.7%
Gr 1-4 HGB, n=51	48 88.9%
Gr 3-4 HGB, n=51	2 3.7%
Gr 0 (no abnormality) ALT, n=46	31 57.4%
Gr 1 (mild) ALT, n=46	10 18.5%
Gr 2 (moderate) ALT, n=46	3 5.6%
Gr 3 (severe) ALT, n=46	2 3.7%
Gr 1-4 ALT, n=46	15 27.8%
Gr 3-4 ALT, n=46	2 3.7%
Gr 0 (no abnormality) AST, n=47	28 51.9%
Gr 1 (mild) AST, n=47	17 31.5%
Gr 3 (severe) AST, n=47	2 3.7%
Gr 1-4 AST, n=47	19 35.2%
Gr 3-4 AST, n=47	2 3.7%
Gr 0 (no abnormality) alkaline phosphatase, n=47	18 33.3%
Gr 1 (mild) alkaline phosphatase, n=47	20 37%
Gr 2 (moderate) alkaline phosphatase, n=47	5 9.3%
Gr 3 (severe) alkaline phosphatase, n=47	4 7.4%
Gr 1-4 alkaline phosphatase, n=47	29 53.7%
Gr 3-4 alkaline phosphatase, n=47	4 7.4%
Gr 0 (no abnormality) total bilirubin, n=48	42 77.8%
Gr 1 (mild) total bilirubin, n=48	1 1.9%
Gr 2 (moderate) total bilirubin, n=48	1 1.9%
Gr 3 (severe) total bilirubin, n=48	4 7.4%
Gr 1-4 total bilirubin, n=48	6 11.1%
Gr 3-4 total bilirubin, n=48	4 7.4%
Gr 0 (no abnormality) creatinine, n=48	45 83.3%
Gr 1 (mild) creatinine, n=48	3 5.6%
Gr 1-4 creatinine, n=48	3 5.6%

11. Secondary Outcome

Title	Number of Participants With Dose Reduction, Dose Delay, or Dose Interruption
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Since the combination of ixabepilone and cetuximab tested in this trial failed to meet the primary objective of sufficiently improving 6-month survival rate relative to historical control in participants with metastatic pancreatic cancer, dose modification data were collected but not summarized.

Arm/Group Title	Ixabepilone	Cetuximab
Arm/Group Description	All participants were administered ixabepilone at a starting dose of 32 mg/m^2 as a 3-hour intravenous (IV) infusion every 3 weeks.	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).
Measure Participants	0	0

12. Secondary Outcome

Title	Percentage of Participants With Baseline Epidermal Growth Factor Receptor (EGFR) Tumor Expression
Description	EGFR expression was evaluated by means of an immunohistochemical assay using tumor tissue collected prior to receiving first dose.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Tissue was available for a small proportion of patients and only 1 out of 11 was EGFR positive, hence EFGR expression analysis was not performed.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	0

13. Secondary Outcome

Title	Change From Baseline in FHSI-8 Total Score by Time-point
Description	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.
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)

Outcome Measure Data

Analysis Population Description

Since the combination of ixabepilone and cetuximab tested in this trial failed to meet the primary objective of sufficiently improving 6-month survival rate relative to historical control in participants with metastatic pancreatic cancer, FHSI-8 score data were collected but not summarized.

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
Measure Participants	0

Adverse Events

Arm/Group Title	Ixabepilone + Cetuximab
Arm/Group Description	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).
All Cause Mortality
	Ixabepilone + Cetuximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ixabepilone + Cetuximab
	Affected / at Risk (%)	# Events
Total	32/54 (59.3%)
Blood and lymphatic system disorders
LEUKOPENIA	1/54 (1.9%)
NEUTROPENIA	2/54 (3.7%)
LEUKOCYTOSIS	1/54 (1.9%)
FEBRILE NEUTROPENIA	2/54 (3.7%)
Cardiac disorders
ATRIAL FIBRILLATION	2/54 (3.7%)
LEFT VENTRICULAR DYSFUNCTION	1/54 (1.9%)
Gastrointestinal disorders
NAUSEA	3/54 (5.6%)
ASCITES	1/54 (1.9%)
VOMITING	4/54 (7.4%)
DIARRHOEA	2/54 (3.7%)
STOMATITIS	1/54 (1.9%)
PANCREATITIS	1/54 (1.9%)
HAEMATOCHEZIA	1/54 (1.9%)
ABDOMINAL MASS	1/54 (1.9%)
ABDOMINAL PAIN	2/54 (3.7%)
INTESTINAL PERFORATION	1/54 (1.9%)
General disorders
CHILLS	1/54 (1.9%)
PYREXIA	3/54 (5.6%)
VISCERAL OEDEMA	1/54 (1.9%)
MULTI-ORGAN FAILURE	1/54 (1.9%)
Hepatobiliary disorders
CHOLANGITIS	1/54 (1.9%)
HYPERBILIRUBINAEMIA	1/54 (1.9%)
Immune system disorders
HYPERSENSITIVITY	3/54 (5.6%)
ANAPHYLACTIC REACTION	1/54 (1.9%)
Infections and infestations
INFECTION	1/54 (1.9%)
PNEUMONIA	1/54 (1.9%)
BACTERAEMIA	1/54 (1.9%)
SEPTIC SHOCK	1/54 (1.9%)
LIVER ABSCESS	1/54 (1.9%)
PYELONEPHRITIS	1/54 (1.9%)
ESCHERICHIA BACTERAEMIA	1/54 (1.9%)
Investigations
WEIGHT DECREASED	1/54 (1.9%)
INTERNATIONAL NORMALISED RATIO INCREASED	1/54 (1.9%)
Metabolism and nutrition disorders
DEHYDRATION	5/54 (9.3%)
HYPOMAGNESAEMIA	2/54 (3.7%)
Musculoskeletal and connective tissue disorders
MYALGIA	1/54 (1.9%)
BACK PAIN	2/54 (3.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PANCREATIC CARCINOMA	6/54 (11.1%)
Nervous system disorders
SYNCOPE	1/54 (1.9%)
HEADACHE	1/54 (1.9%)
PARAESTHESIA	1/54 (1.9%)
Psychiatric disorders
CONFUSIONAL STATE	1/54 (1.9%)
MENTAL STATUS CHANGES	1/54 (1.9%)
Renal and urinary disorders
RENAL FAILURE	1/54 (1.9%)
Respiratory, thoracic and mediastinal disorders
HYPOXIA	1/54 (1.9%)
DYSPNOEA	2/54 (3.7%)
PULMONARY EMBOLISM	2/54 (3.7%)
RESPIRATORY FAILURE	1/54 (1.9%)
Vascular disorders
HYPOTENSION	6/54 (11.1%)
DEEP VEIN THROMBOSIS	2/54 (3.7%)
ORTHOSTATIC HYPOTENSION	1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	Ixabepilone + Cetuximab
	Affected / at Risk (%)	# Events
Total	49/54 (90.7%)
Blood and lymphatic system disorders
ANAEMIA	14/54 (25.9%)
LEUKOPENIA	8/54 (14.8%)
LYMPHOPENIA	4/54 (7.4%)
NEUTROPENIA	11/54 (20.4%)
THROMBOCYTOPENIA	3/54 (5.6%)
Gastrointestinal disorders
NAUSEA	25/54 (46.3%)
ASCITES	6/54 (11.1%)
VOMITING	18/54 (33.3%)
DIARRHOEA	22/54 (40.7%)
FLATULENCE	8/54 (14.8%)
STOMATITIS	8/54 (14.8%)
CONSTIPATION	20/54 (37%)
ABDOMINAL PAIN	17/54 (31.5%)
ABDOMINAL DISCOMFORT	3/54 (5.6%)
ABDOMINAL DISTENSION	4/54 (7.4%)
ABDOMINAL PAIN UPPER	4/54 (7.4%)
General disorders
CHILLS	3/54 (5.6%)
FATIGUE	34/54 (63%)
PYREXIA	9/54 (16.7%)
ASTHENIA	5/54 (9.3%)
OEDEMA PERIPHERAL	7/54 (13%)
MUCOSAL INFLAMMATION	9/54 (16.7%)
Immune system disorders
HYPERSENSITIVITY	5/54 (9.3%)
Infections and infestations
PARONYCHIA	4/54 (7.4%)
URINARY TRACT INFECTION	4/54 (7.4%)
Investigations
WEIGHT DECREASED	11/54 (20.4%)
ALANINE AMINOTRANSFERASE INCREASED	4/54 (7.4%)
ASPARTATE AMINOTRANSFERASE INCREASED	4/54 (7.4%)
BLOOD ALKALINE PHOSPHATASE INCREASED	6/54 (11.1%)
Metabolism and nutrition disorders
ANOREXIA	17/54 (31.5%)
DEHYDRATION	7/54 (13%)
HYPOKALAEMIA	4/54 (7.4%)
HYPERKALAEMIA	3/54 (5.6%)
HYPERGLYCAEMIA	3/54 (5.6%)
HYPOMAGNESAEMIA	17/54 (31.5%)
Musculoskeletal and connective tissue disorders
MYALGIA	3/54 (5.6%)
BACK PAIN	9/54 (16.7%)
PAIN IN EXTREMITY	4/54 (7.4%)
MUSCULOSKELETAL PAIN	3/54 (5.6%)
Nervous system disorders
HEADACHE	5/54 (9.3%)
DIZZINESS	9/54 (16.7%)
DYSGEUSIA	3/54 (5.6%)
PARAESTHESIA	5/54 (9.3%)
NEUROPATHY PERIPHERAL	4/54 (7.4%)
PERIPHERAL SENSORY NEUROPATHY	6/54 (11.1%)
Psychiatric disorders
ANXIETY	6/54 (11.1%)
INSOMNIA	9/54 (16.7%)
DEPRESSION	6/54 (11.1%)
Renal and urinary disorders
DYSURIA	4/54 (7.4%)
Respiratory, thoracic and mediastinal disorders
COUGH	6/54 (11.1%)
DYSPNOEA	8/54 (14.8%)
EPISTAXIS	4/54 (7.4%)
OROPHARYNGEAL PAIN	3/54 (5.6%)
Skin and subcutaneous tissue disorders
RASH	5/54 (9.3%)
ALOPECIA	25/54 (46.3%)
DRY SKIN	7/54 (13%)
PRURITUS	4/54 (7.4%)
DERMATITIS ACNEIFORM	29/54 (53.7%)
Vascular disorders
HYPOTENSION	8/54 (14.8%)

Limitations/Caveats

Study CA163-116 was completed; however, the combination tested in this trial failed to meet the primary objective to demonstrate a 6-month survival rate greater than 50% in participants with metastatic pancreatic cancer.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.