QUILT-2.019: A Study of AMG 655 or AMG 479 in Combination With Gemcitabine for Treatment of Metastatic Pancreatic Cancer

Phase 1

Completed

Conditions: Metastatic Pancreatic Cancer
Pancreatic Cancer
Adenocarcinoma of the Pancreas

Interventions: Drug: AMG 655
Drug: AMG 479
Other: Placebo

Registration Number: NCT00630552

Lead Sponsor: NantCell, Inc.

Brief Summary: This is a multi-center, 2-part study of AMG 655, AMG 479 or AMG 655-placebo plus gemcitabine as first-line treatment of subjects with metastatic pancreatic cancer. Part 1 is an open-label, dose-escalation phase 1b segment to determine the safety, tolerability and maximum tolerated dose of AMG 655 in combination with gemcitabine. Enrollment into part 1 of the study has been completed. Part 2 is a randomized, placebo-controlled phase 2 segment to estimate the efficacy as assessed by 6 month survival of AMG 655, AMG 479, or AMG 655-placebo in combination with gemcitabine. The phase 2 segment that will commence after dose selection in part 1. In part 2, subjects will be randomized 1:1:1 to AMG 655, AMG 479, or placebo in combination with gemcitabine.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 138

Inclusion Criteria

Untreated metastatic adenocarcinoma of the pancreas (AJCC Stage IV)
Subjects with unresectable pancreatic cancer who have had surgery are eligible if fully recovered and greater than 30 days have elapsed since the surgery.

Subjects with a history of pancreatoduodenectomy are eligible provided that there is radiographically documented disease recurrence.

Men or women ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
Adequate hematologic, hepatic, renal and coagulation function
Amylase and lipase ≤ 2.0 x ULN
Adequately controlled type 1 or 2 diabetic subjects

Exclusion Criteria

Islet cell, acinar cell carcinoma, non-adenocarcinoma (eg, lymphoma, sarcoma, etc), adenocarcinoma originated from biliary tree or cystadenocarcinoma
Known central nervous system metastases
Uncontrolled cardiac disease or any other co-morbid disease that would increase the risk of toxicity
Adjuvant chemotherapy or chemoradiotherapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1b AMG 655 3mg/kg	AMG 655	Subjects were treated with one of 2 dose levels of AMG 655 (3 mg/kg) with gemcitabine.
Phase 1b AMG 655 10mg/kg	AMG 655	Subjects were treated with one of 2 dose levels of AMG 655 (10 mg/kg) with gemcitabine.
Phase 2 AMG 655	AMG 655	Subjects were treated with the dose of AMG 655 (10mg/kg) in combination with gemcitabine. Gemcitabine (1000 mg/m2) was administered by intravenous infusion on days 1, 8 and 15 of each 28 day cycle followed by the AMG 655 infusion on days 1 and 15 after completion of the gemcitabine infusion.
Phase 2 AMG 479	AMG 479	Subjects were treated with the dose of AMG 479 (12 mg/kg) in combination with gemcitabine. Gemcitabine (1000 mg/m2) was administered by intravenous infusion on days 1, 8 and 15 of each 28 day cycle followed by the AMG 479 infusion on days 1 and 15 after completion of the gemcitabine infusion.
Phase 2 AMG 655-placebo	Placebo	Subjects were treated with the dose of AMG 655-placebo in combination with gemcitabine. Gemcitabine (1000 mg/m2) was administered by intravenous infusion on days 1, 8 and 15 of each 28 day cycle followed by the AMG 655-placebo infusion on days 1 and 15 after completion of the gemcitabine infusion.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities (DLTs; Phase 1b Portion Only)	28 days	The incidence of adverse events and clinical laboratory abnormalities defined as DLTs. A DLT was defined as any grade 3 or higher hematologic or non-hematologic toxicity related to any study treatment.
Six Month Overall Survival Rate (Phase 2 Portion Only)	6 months	The proportion of subjects alive at 6 months

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	From start of study treatment through up to 36 months	Objective response was defined as a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors \[RECIST\] and was determined only for subjects with measurable disease at baseline. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progression-free Survival (PFS)	From start of study treatment through up to 36 months	PFS was defined as the time from study day 1 (phase 1b portion) or randomization (phase 2 portion) to the first observation of disease progression per investigator review (as classified by modified RECIST or clinical progression, whichever occurred first) or death due to any cause, or censoring. Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.
Overall Survival	From start of study treatment through up to 36 months	Overall survival was defined as the time from study day 1 (phase 1b portion) or randomization (phase 2 portion) to death for any cause.
Number of Subjects With an Adverse Event	From start of study treatment through up to 44 weeks	Graded Using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 3.0
Pharmacokinetics of AMG 655, Ganitumab, and Gemcitabine	From start of study treatment through up to 48 weeks	PK parameter of Cmax for AMG 655 (phase 1b and phase 2 portions) - pg 266, ganitumab (phase 2 portion only) - pg 270 , and gemcitabine (phase 1b portion only - pg 272) PK parameters
Dose Intensity of Gemcitabine (Phase 2 Portion Only)	From start of study treatment through up to 40 weeks	Average Dose intensity of gemcitabine when combined with AMG 655, placebo or AMG 479
Duration of Response	From objective response through up to 36 months	Duration of response was the time from the first observation of an objective response to the subsequent time of disease progression (per modified RECIST or clinical progression, whichever came first) or death due to any cause. Objective response = a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors \[RECIST\]. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Incidence of Antibody Formation	From start of treatment up to 40 weeks	The incidence of antibody formation of anti-AMG 655 (phase 1b and phase 2 portions) or anti- ganitumab (phase 2 portion only)