Clinical trial NCT00630552: QUILT-2.019: A Study of AMG 655 or AMG 479 in Combination With Gemcitabine for Treatment of Metastatic Pancreatic Cancer
Official title: A Phase 1b/2 Study to Evaluate the Safety and Efficacy of AMG 655 or AMG 479 in Combination With Gemcitabine as First-Line Therapy for Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Adenocarcinoma of the Pancreas
Metastatic Pancreatic Cancer
Pancreatic Cancer
Keywords: AMG 479
Gemcitabine
TR-2
IGF-1R
AMG 655
Pancreatic cancer
Adenocarcinoma of the Pancreas
Metastatic Pancreatic Cancer
Lead sponsor: NantCell, Inc.
Sponsor class: INDUSTRY
First posted: 2008-03-07
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs; Phase 1b Portion Only)
timeFrame: 28 days
measure: Six Month Overall Survival Rate (Phase 2 Portion Only)
timeFrame: 6 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: From start of study treatment through up to 36 months
measure: Progression-free Survival (PFS)
timeFrame: From start of study treatment through up to 36 months
measure: Overall Survival
timeFrame: From start of study treatment through up to 36 months
measure: Number of Subjects With an Adverse Event
timeFrame: From start of study treatment through up to 44 weeks
measure: Pharmacokinetics of AMG 655, Ganitumab, and Gemcitabine
timeFrame: From start of study treatment through up to 48 weeks
measure: Dose Intensity of Gemcitabine (Phase 2 Portion Only)
timeFrame: From start of study treatment through up to 40 weeks
measure: Duration of Response
timeFrame: From objective response through up to 36 months
measure: Incidence of Antibody Formation
timeFrame: From start of treatment up to 40 weeks
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Research Site
state: California
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Northridge
country: United States
facility: Research Site
state: California
city: Oxnard
country: United States
facility: Research Site
state: California
city: Rancho Mirage
country: United States
facility: Research Site
state: California
city: Redondo Beach
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Santa Maria
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Harvey
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Westminster
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Henderson
country: United States
facility: Research Site
state: Nevada
city: Albany
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Hickory
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Eugene
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Austin
country: United States
facility: Research Site
state: Texas
city: Austin
country: United States
facility: Research Site
state: Texas
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Yakima
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Cella D, Butt Z, Kindler HL, Fuchs CS, Bray S, Barlev A, Oglesby A. Validity of the FACT Hepatobiliary (FACT-Hep) questionnaire for assessing disease-related symptoms and health-related quality of life in patients with metastatic pancreatic cancer. Qual Life Res. 2013 Jun;22(5):1105-12. doi: 10.1007/s11136-012-0217-4. Epub 2012 Jun 8.
citation: Kindler HL, Richards DA, Garbo LE, Garon EB, Stephenson JJ Jr, Rocha-Lima CM, Safran H, Chan D, Kocs DM, Galimi F, McGreivy J, Bray SL, Hei Y, Feigal EG, Loh E, Fuchs CS. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol. 2012 Nov;23(11):2834-2842. doi: 10.1093/annonc/mds142. Epub 2012 Jun 13.
citation: Lu, JF.Exposure-response analysis to facilitate phase 3 dose selection for Ganitumumab (AMG 479) in combination with Gemcitabine to treat metastatic pancreatic cancer.Journal-000728;
citation: McCaffery I, Tudor Y, Deng H, Tang R, Suzuki S, Badola S, Kindler HL, Fuchs CS, Loh E, Patterson SD, Chen L, Gansert JL. Putative predictive biomarkers of survival in patients with metastatic pancreatic adenocarcinoma treated with gemcitabine and ganitumab, an IGF1R inhibitor. Clin Cancer Res. 2013 Aug 1;19(15):4282-9. doi: 10.1158/1078-0432.CCR-12-1840. Epub 2013 Jun 5.
citation: TBD.Validation of the FACT-hepatobiliary questionnaire in metastatic pancreatic cancer population.Journal-004521;