Ganitumab in Locally Advanced Unresectable Adenocarcinoma of the Pancreas

Phase 2

Terminated

Conditions: Unresectable
Adenocarcinoma of the Pancreas
Locally Advanced

Interventions: Drug: Gemcitabine
Drug: Placebo
Drug: AMG 479

Registration Number: NCT01318642

Lead Sponsor: NantBioScience, Inc.

Brief Summary: This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1).

Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.

Detailed Description: This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1).

Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Subjects must have histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is unresectable, per institutional practice
Radiologically measurable and/or non-measurable disease as defined by RECIST version 1.1
Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
Men or women >/= 18 years of age
Adequate organ function

Exclusion Criteria

Early (stage I) or metastatic (stage IV) disease
Islet cell, acinar cell carcinoma, non-adenocarcinoma, (eg, lymphoma, sarcoma, etc), adenocarcinoma originating from biliary tree or cystadenocarcinoma
External biliary drain
Currently treated or previously treated with biologic, small molecule, immunotherapy, chemotherapy (ie, including gemcitabine), or other agents for pancreatic cancer
Currently treated or previously treated with radiotherapy, or chemoradiotherapy for pancreatic cancer

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Gemcitabine	Placebo	Arm 2: AMG479-placebo IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle
AMG 479 20 mg/kg + Gemcitabine	AMG 479	ARM 1: AMG 479 20mg/kg IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle.
Placebo + Gemcitabine	Gemcitabine	Arm 2: AMG479-placebo IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle
AMG 479 20 mg/kg + Gemcitabine	Gemcitabine	ARM 1: AMG 479 20mg/kg IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle.

Primary Outcome Measures

Name	Time	Method
The Primary Endpoint is Progression-free Survival (PFS) as Defined as the Time From Randomization to Progression (Per RECIST v1.1) or Death.	From randomization to the date of either disease progression or death, up to 181 days progression or death	The time from randomization to progression (per RECIST version 1.1) or death from any cause. 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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 181 days	OS - time from study day 1 to death (by any cause)
Number of Participants With Adverse Events	Up to 4 months	Measured via CTCAE v3.0
Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate	Up to 181 days	PFS rates - subjects with disease progression (PD) or death at the timepoint; OS rates - subjects alive at the timepoint; ORR - tumor response assessment of either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST); DCR - subjects with PR, CR, or SD Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed
Duration of Response	Up to 181 days	DOR - time from the first observation of an objective response (subjects with CR or PR) to the time of PD or death; Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed
Number of Participants With Anti-AMG 479 Antibodies	Up to 181 days	post-dose anti-AMG 479 antibody positive rate