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

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

Population: 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.

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)

Population: 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.

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)

Population: 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.

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).

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

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).

Population: 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.

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

Population: 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.

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.

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

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.

Population: 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.

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.

Population: 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.

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.

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

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.

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

EGFR expression was evaluated by means of an immunohistochemical assay using tumor tissue collected prior to receiving first dose.

Time frame: Baseline

Population: 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.

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

Population: 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.