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

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

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 Overview

• Status: Completed
• Conditions: Pancreatic Cancer; Adenocarcinoma of the Pancreas; Metastatic Pancreatic Cancer
• Intervention / Treatment: Other: Placebo; Drug: AMG 655; Drug: AMG 479

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Alhambra, California, United States, 91801
      • Research Site
    • Bakersfield, California, United States, 93309
      • Research Site
    • Fullerton, California, United States, 92835
      • Research Site
    • La Jolla, California, United States, 92093
      • Research Site
    • Long Beach, California, United States, 90813
      • Research Site
    • Los Angeles, California, United States, 90095
      • Research Site
    • Northridge, California, United States, 91328
      • Research Site
    • Oxnard, California, United States, 93030
      • Research Site
    • Rancho Mirage, California, United States, 92270
      • Research Site
    • Redondo Beach, California, United States, 90277
      • Research Site
    • San Francisco, California, United States, 94115
      • Research Site
    • Santa Maria, California, United States, 93454
      • Research Site
    • Santa Monica, California, United States, 90403
      • Research Site
  • Florida
    • Miami, Florida, United States, 33136
      • Research Site
    • Orlando, Florida, United States, 32804
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Research Site
    • Atlanta, Georgia, United States, 30341
      • Research Site
    • Marietta, Georgia, United States, 30060
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
    • Harvey, Illinois, United States, 60426
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Research Site
    • Westminster, Maryland, United States, 21157
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Research Site
  • New York
    • Albany, New York, United States, 12206
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
    • Hickory, North Carolina, United States, 28602
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Research Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15261
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Research Site
    • Austin, Texas, United States, 78705
      • Research Site
    • Austin, Texas, United States, 78731
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
    • Round Rock, Texas, United States, 78681
      • Research Site
    • Tyler, Texas, United States, 75702
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site
    • Yakima, Washington, United States, 98902
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b AMG 655 3mg/kg; Subjects were treated with one of 2 dose levels of AMG 655 (3 mg/kg) with gemcitabine.	Drug: AMG 655; AMG 655 is a fully human monoclonal agonist antibody directed against TRAIL Receptor 2 (TR-2).
Experimental: Phase 1b AMG 655 10mg/kg; Subjects were treated with one of 2 dose levels of AMG 655 (10 mg/kg) with gemcitabine.	Drug: AMG 655; AMG 655 is a fully human monoclonal agonist antibody directed against TRAIL Receptor 2 (TR-2).
Experimental: Phase 2 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.	Drug: AMG 655; AMG 655 is a fully human monoclonal agonist antibody directed against TRAIL Receptor 2 (TR-2).
Experimental: Phase 2 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.	Drug: AMG 479; AMG 479 is fully human monoclonal antagonist antibody targeted against insulin-like growth factor receptor type 1 (IGF-1R).
Placebo Comparator: Phase 2 AMG 655-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.	Other: Placebo; Inactive dummy of AMG 655.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	28 days
Six Month Overall Survival Rate (Phase 2 Portion Only)	The proportion of subjects alive at 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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	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	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	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.	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)	From start of treatment up to 40 weeks

Collaborators and Investigators

• Sponsor: NantCell, Inc.
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.
• 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.
• 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;
• 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.
• TBD.Validation of the FACT-hepatobiliary questionnaire in metastatic pancreatic cancer population.Journal-004521;

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 28, 2008
• First Submitted That Met QC Criteria: February 28, 2008
• First Posted (Estimated): March 7, 2008

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; Pancreatic cancer; AMG 479; Metastatic Pancreatic Cancer; Adenocarcinoma of the Pancreas; AMG 655; IGF-1R; TR-2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Conatumumab
• Other Study ID Numbers: 20060323; QUILT-2.019 (Other Identifier: NantCell, Inc.)