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

NantCell, Inc.138 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

138

Conditions

Adenocarcinoma of the Pancreas Metastatic Pancreatic Cancer Pancreatic Cancer

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs; Phase 1b Portion Only)

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.

Time frame: 28 days

Six Month Overall Survival Rate (Phase 2 Portion Only)

The proportion of subjects alive at 6 months

Time frame: 6 months

Secondary Outcomes

Objective Response Rate

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.

Time frame: From start of study treatment through up to 36 months

Progression-free Survival (PFS)

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.

Time frame: From start of study treatment through up to 36 months

Overall Survival

Overall survival was defined as the time from study day 1 (phase 1b portion) or randomization (phase 2 portion) to death for any cause.

Time frame: From start of study treatment through up to 36 months

Number of Subjects With an Adverse Event

Graded Using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 3.0

Time frame: From start of study treatment through up to 44 weeks

Pharmacokinetics of AMG 655, Ganitumab, and Gemcitabine

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

Time frame: From start of study treatment through up to 48 weeks

Dose Intensity of Gemcitabine (Phase 2 Portion Only)

Average Dose intensity of gemcitabine when combined with AMG 655, placebo or AMG 479

Time frame: From start of study treatment through up to 40 weeks

Duration of Response

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.

Time frame: From objective response through up to 36 months

Incidence of Antibody Formation

The incidence of antibody formation of anti-AMG 655 (phase 1b and phase 2 portions) or anti- ganitumab (phase 2 portion only)

Time frame: From start of treatment up to 40 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (44)

Outcomes

Primary Outcomes

Secondary Outcomes