Open-label Study of CS-1008 for Subjects With Untreated and Unresectable Pancreatic Cancer

Phase 2

Completed

Conditions: Pancreatic Cancer

Interventions: Drug: CS-1008 (humanized anti-DR5 antibody)
Drug: gemcitabine

Registration Number: NCT00521404

Lead Sponsor: Daiichi Sankyo

Brief Summary: Phase 2 study to determine the efficacy and safety of CS-1008 when given with gemcitabine to subjects with previously untreated and unresectable (unable to be surgically removed) or metastatic (spread to other areas beyond the pancreas) pancreatic cancer.

Detailed Description: Primary Objective:

- To evaluate the efficacy of CS-1008 administered in combination with gemcitabine to chemotherapy naive subjects with unresectable or metastatic pancreatic cancer, based on the progression-free survival at 16 weeks.

Secondary Objectives:

* To evaluate the efficacy of CS-1008 administered in combination with gemcitabine on overall progression-free survival rate, objective response rate, duration of response, and overall survival.

* To determine the pharmacokinetics of BIP CS-1008 and DSC CS-1008.

* To study potential biomarkers of CS-1008 activity

* To assess possible human anti-human antibody formation after exposure to CS-1008

* To evaluate the safety profile of CS-1008 when administered in combination with gemcitabine to chemotherapy naive subjects with unresectable or metastatic pancreatic cancer.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 65

Inclusion Criteria

Histologically or cytologically confirmed resectable or metastatic pancreatic cancer; not previously treated with chemotherapy; measurable disease; 18 years of age or older

Exclusion Criteria

Anticipation of need for major surgery or radiation therapy during the study
Heart Disease exclusions: myocardial infarction or unstable angina within the past 6 months; severe or unstable angina pectoris within the past 6 months; coronary or peripheral artery bypass graft within the past 6 mo., etc.
Clinically significant active infection or history of HIV
Partial or complete bowel obstruction
Poorly controlled psychiatric illness

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CS-1008 + gemcitabine	CS-1008 (humanized anti-DR5 antibody)	CS-1008 + gemcitabine
CS-1008 + gemcitabine	gemcitabine	CS-1008 + gemcitabine

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival Rate at 16 Weeks Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer	Baseline to the date of disease progression or death due to any cause (whichever occurs first), up to 16 weeks post dose.	Progression-free survival rate (PFS) was defined as the time from the date of the first administration of the study drug (Day 1) to the date of the first objective documentation of disease progression or death resulting from any cause, whichever came first at 16 weeks post-treatment with CS-1008.

Secondary Outcome Measures

Name	Time	Method
Kaplan-Meier (Non-Parametric) Analysis of Progression-Free Survival Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer	Baseline up to date of disease progression or death due to any cause (whichever occurs first), up to approximately 36 months post dose.	PFS (Progression-free survival) was defined as the time from the date of the first administration of study drug (Day 1) to the date of the first objective documentation of disease progression or death resulting from any cause, whichever came first.
Overall Survival Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer	Baseline to death due to any cause, up to approximately 36 months post dose.	OS (Overall Survival) was defined as the time from the date of the first administration of study drug (Day 1) to the date of death. If there was no death reported for a subject before the cut-off date for overall survival analysis, overall survival was censored at the last contact date at which the subject was known to be alive.
Best Overall Tumor Response Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer	Baseline to up to date of first documented objective response or disease progression (whichever occurs first), up to approximately 36 months post dose.	The best overall response the best response (in the order of confirmed complete response \[CR\], confirmed partial response \[PR\], unconfirmed CR, unconfirmed PR, stable disease \[SD\], and progressive disease\[PD\]) among all overall responses recorded from the start of treatment until the subject withdrew from the study. If there was no tumor assessment after the first infusion of study drug and no clinical disease progression recorded, the best overall response was classified as Unknown. CR was defined as the disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, PD was defined as at least a 20% increase in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease PD according to RECIST guideline (version 1.1).
Number of Participants With Treatment-Emergent Adverse Events Considered by the Investigator at Least Possibly Related to CS-1008 Experienced by ≥5% of Participants by System Organ Class and Preferred Term	Baseline up to 30 days post last dose, up to approximately 36 months post dose.	A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that: emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment or worsens in severity during treatment relative to the pre-treatment state when the AE was continuous. The AEs with an onset date on Day 1 (the date on which the first dose of study medication was administered) were counted as a TEAE. An AE that occurred more than 30 days after the last dose of study medication was not included as a TEAE unless it was considered drug-related. A TEAE was considered related to CS-1008 or gemcitabine if the investigator considered the event as possibly, probably, or definitely related to treatment, or if the investigator's assessment of the relationship was unknown.
Number of Participants With Treatment-Emergent Adverse Events Considered by the Investigator at Least Possibly Related to Gemcitabine Experienced by ≥5% of Participants by System Organ Class and Preferred Term	Baseline up to 30 days post last dose, up to approximately 36 months post dose.	A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that: emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment or worsens in severity during treatment relative to the pre-treatment state when the AE was continuous. The AEs with an onset date on Day 1 (the date on which the first dose of study medication was administered) were counted as a TEAE. An AE that occurred more than 30 days after the last dose of study medication was not included as a TEAE unless it was considered drug-related. A TEAE was considered related to CS-1008 or gemcitabine if the investigator considered the event as possibly, probably, or definitely related to treatment, or if the investigator's assessment of the relationship was unknown.