S0727 Gemcitabine Hydrochloride and Erlotinib Hydrochloride With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery
- Conditions
- Stage IV Pancreatic Cancer
- Interventions
- Registration Number
- NCT00617708
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase I/II trial is studying the side effects and best dose of monoclonal antibody therapy when given together with gemcitabine hydrochloride and erlotinib hydrochloride and to see how well they work compared with giving gemcitabine hydrochloride and erlotinib hydrochloride alone as first-line therapy in treating patients with metastatic pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving erlotinib hydrochloride and gemcitabine hydrochloride together with monoclonal antibody therapy may kill more tumor cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To assess the appropriate dose of IMC-A12 (cixutumumab) to use in combination with gemcitabine (gemcitabine hydrochloride) and erlotinib (erlotinib hydrochloride). (Phase I) II. To assess progression-free survival in patients with metastatic pancreatic cancer treated with IMC-A12 plus gemcitabine and erlotinib compared to those treated with gemcitabine plus erlotinib alone. (Phase II) III. To assess overall survival in each of the two treatment arms in this group of patients. (Phase II) IV. To assess the total response probability (confirmed and unconfirmed, complete and partial responses) in each of the two treatment arms in the subset of this group of patients with measurable disease. (Phase II) V. To assess the qualitative and quantitative toxicities in each of the two treatment arms in this group of patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of cixutumumab followed by a randomized, phase II study.
Patients are initially enrolled into the phase I portion of the study to determine the recommended phase II dose (RPTD) of cixutumumab. Once the RPTD is determined, patients are enrolled into the phase II portion of the study.
PHASE I (LIMITED INSTITUTIONS): Patients receive erlotinib hydrochloride orally (PO) once daily on days 1-28, gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
PHASE II (ALL SWOG MEMBERS): Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive erlotinib hydrochloride, gemcitabine hydrochloride, and cixutumumab at the RPTD as in phase I.
ARM II: Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Previously collected tumor tissue is obtained for gene expression analyses by RT-PCR, RNA isolation, and cDNA synthesis. Blood samples are collected periodically for correlative studies. Samples are assessed for the potential relationship between gene expression levels, germline polymorphisms, Ras and P13K mutations and progression-free survival and overall survival.
After completion of study treatment, patients are followed every 6 months for up to 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 134
-
Histologically or cytologically confirmed pancreatic adenocarcinoma
- Stage IV disease (any T, any N, M1 [distant metastases])
- Unresectable disease
- Histologic diagnosis based on a metastatic site must be compatible with pancreatic cancer
-
Measurable and/or nonmeasurable disease
-
No endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer
-
No macroscopic residual disease post-resection as the only site of disease
-
No clinically significant ascites
-
No known brain metastases
- Patients with neurologic signs or symptoms must undergo brain imaging studies AND studies must be negative for disease
-
Zubrod performance status 0-1
-
ANC ≥ 1,500/mcL
-
Platelet count ≥ 100,000/mcL
-
Hemoglobin ≥ 9 g/dL
-
Leukocytes ≥ 3,000/mcL
-
Total bilirubin normal
-
SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)
-
Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
-
Fasting serum glucose < 120 mg/dL or below the ULN
- Patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition
-
INR ≤ 1.5 and PTT ≤ 5 seconds above ULN
-
Not pregnant or nursing
-
Fertile patients must use effective contraception
-
Willing to submit previously collected tumor tissue specimens
-
No history of allergic reaction attributed to compounds of similar chemical or biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12
-
No active acute or chronic infections requiring antibiotics
-
No significant ongoing cardiac problems, including any of the following:
- Myocardial infarction within the past 6 months
- Uncontrolled hypertension
- Unstable angina
- Uncontrolled arrhythmia
- Congestive heart failure
-
No known HIV infection
-
No other prior malignancy, except for the following:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Adequately treated stage I or II cancer from which the patient is currently in complete remission
- Any other cancer from which the patient has been disease-free for 5 years
-
At least 14 days since prior surgery
-
At least 28 days since prior radiotherapy for palliation to metastatic sites
- Patient must have other untreated metastatic sites that would qualify them for this protocol
-
At least 6 months since prior adjuvant chemotherapy
-
No prior chemotherapy, hormonal therapy, immunotherapy, or chemoradiotherapy for advanced or locally advanced pancreatic cancer, including drugs that target either EGFR or IGFR
-
No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of cancer
-
No prior gemcitabine hydrochloride
-
No prior chimerized or murine monoclonal antibody therapy
-
No concurrent CYP3A4 inducers including, but not limited to, any of the following:
- Rifampicin
- Rifabutin
- Rifapentine
- Phenytoin
- Carbamazepine
- Phenobarbital
- Hypericum perforatum (St. John's wort)
-
No concurrent CYP3A4 inhibitors including, but not limited to, any of the following:
- Atazanavir
- Clarithromycin
- Indinavir
- Itraconazole
- Ketoconazole
- Nefazodone
- Nelfinavir
- Ritonavir
- Saquinavir
- Telithromycin
- Troleandomycin
- Voriconazole
-
Concurrent prophylactic low-dose coumadin or low molecular weight heparin allowed provided coagulation criteria are met
-
Full-dose anticoagulation allowed provided coagulation criteria are met and are under strict control and monitoring
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (erlotinib, gemcitabine, cixutumumab) erlotinib hydrochloride Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (erlotinib, gemcitabine) erlotinib hydrochloride Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (erlotinib, gemcitabine) gemcitabine hydrochloride Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (erlotinib, gemcitabine, cixutumumab) cixutumumab Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (erlotinib, gemcitabine, cixutumumab) gemcitabine hydrochloride Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose Determination 28 days Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).
Progression-Free Survival Up to 3 years From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
- Secondary Outcome Measures
Name Time Method Overall Survival Up to 3 years From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Response Up to 3 years Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Toxicity Up to 3 years Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Trial Locations
- Locations (146)
Shawnee Mission Medical Center
🇺🇸Shawnee Mission, Kansas, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Mecosta County Medical Center
🇺🇸Big Rapids, Michigan, United States
Grand Rapids Clinical Oncology Program
🇺🇸Grand Rapids, Michigan, United States
Mercy Health Partners-Mercy Campus
🇺🇸Muskegon, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Atlanta Regional CCOP
🇺🇸Atlanta, Georgia, United States
Saint Joseph's Hospital of Atlanta
🇺🇸Atlanta, Georgia, United States
Wellstar Kennestone Hospital
🇺🇸Marietta, Georgia, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Saint Luke's South Hospital
🇺🇸Overland Park, Kansas, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Kalispell Medical Oncology
🇺🇸Kalispell, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Community Medical Hospital
🇺🇸Missoula, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸Missoula, Montana, United States
Cone Health Cancer Center
🇺🇸Greensboro, North Carolina, United States
Wenatchee Valley Medical Center
🇺🇸Wenatchee, Washington, United States
NEA Baptist Memorial Hospital
🇺🇸Jonesboro, Arkansas, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Northern Rockies Radiation Oncology Center
🇺🇸Billings, Montana, United States
Hematology-Oncology Centers of the Northern Rockies PC
🇺🇸Billings, Montana, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
Berdeaux, Donald MD (UIA Investigator)
🇺🇸Great Falls, Montana, United States
Saint Peter's Community Hospital
🇺🇸Helena, Montana, United States
Glacier Oncology PLLC
🇺🇸Kalispell, Montana, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Veterans Administration Medical Center
🇺🇸Houston, Texas, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Metro Health Hospital
🇺🇸Wyoming, Michigan, United States
Veterans Administration Medical Center - Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Saint Joseph Oncology Inc
🇺🇸Saint Joseph, Missouri, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Northern Montana Hospital
🇺🇸Havre, Montana, United States
Akron General Medical Center
🇺🇸Akron, Ohio, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Ben Taub General Hospital
🇺🇸Houston, Texas, United States
University of Texas Medical Branch at Galveston
🇺🇸Galveston, Texas, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Harrison Poulsbo Hematology and Oncology
🇺🇸Poulsbo, Washington, United States
Dixie Medical Center Regional Cancer Center
🇺🇸Saint George, Utah, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Harrison Bremerton Hematology and Oncology
🇺🇸Bremerton, Washington, United States
Intermountain Health Care
🇺🇸Salt Lake City, Utah, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of Rochester
🇺🇸Rochester, New York, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Methodist Hospital
🇺🇸Houston, Texas, United States
Annie Penn Memorial Hospital
🇺🇸Reidsville, North Carolina, United States
The Don and Sybil Harrington Cancer Center
🇺🇸Amarillo, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Sandra L Maxwell Cancer Center
🇺🇸Cedar City, Utah, United States
American Fork Hospital
🇺🇸American Fork, Utah, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸Seattle, Washington, United States
Utah Cancer Specialists-Salt Lake City
🇺🇸Salt Lake City, Utah, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Memorial Hospital Of Martinsville
🇺🇸Martinsville, Virginia, United States
Minor and James Medical PLLC
🇺🇸Seattle, Washington, United States
Columbia Basin Hematology and Oncology PLLC
🇺🇸Kennewick, Washington, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States
The Polyclinic
🇺🇸Seattle, Washington, United States
Rocky Mountain Oncology
🇺🇸Casper, Wyoming, United States
Valley Medical Oncology Consultants-Castro Valley
🇺🇸Castro Valley, California, United States
Contra Costa Regional Medical Center
🇺🇸Martinez, California, United States
El Camino Hospital
🇺🇸Mountain View, California, United States
Bay Area Breast Surgeons Inc
🇺🇸Oakland, California, United States
Mills - Peninsula Hospitals
🇺🇸Burlingame, California, United States
Eden Hospital Medical Center
🇺🇸Castro Valley, California, United States
Glendale Memorial Hospital and Health Center
🇺🇸Glendale, California, United States
East Bay Radiation Oncology Center
🇺🇸Castro Valley, California, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Highland General Hospital
🇺🇸Oakland, California, United States
Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Tom K Lee Inc
🇺🇸Oakland, California, United States
Sutter Solano Medical Center
🇺🇸Vallejo, California, United States
University of California Medical Center At Irvine-Orange Campus
🇺🇸Orange, California, United States
Valley Medical Oncology Consultants
🇺🇸Pleasanton, California, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Well Star Cobb Hospital
🇺🇸Austell, Georgia, United States
Southern Regional Medical Center
🇺🇸Riverdale, Georgia, United States
Harbin Clinic Medical Oncology and Clinical Research
🇺🇸Rome, Georgia, United States
John B Amos Cancer Center
🇺🇸Columbus, Georgia, United States
Saint Joseph's-Candler Health System
🇺🇸Savannah, Georgia, United States
Cancer Care Center of Decatur
🇺🇸Decatur, Illinois, United States
Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
Christus Saint Frances Cabrini Hospital
🇺🇸Alexandria, Louisiana, United States
Heartland Hematology and Oncology Associates Incorporated
🇺🇸Kansas City, Missouri, United States
Montana Cancer Consortium CCOP
🇺🇸Billings, Montana, United States
Bozeman Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸Kansas City, Missouri, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸Butte, Montana, United States
Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Arnot Ogden Medical Center
🇺🇸Elmira, New York, United States
Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
Saint Vincent Healthcare
🇺🇸Billings, Montana, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Interlakes Foundation Inc-Rochester
🇺🇸Rochester, New York, United States
Montana Cancer Specialists
🇺🇸Missoula, Montana, United States
McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
Randolph Hospital
🇺🇸Asheboro, North Carolina, United States
Skagit Valley Hospital
🇺🇸Mount Vernon, Washington, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Highland Hospital
🇺🇸Rochester, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Logan Regional Hospital
🇺🇸Logan, Utah, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
North Kansas City Hospital
🇺🇸Kansas City, Missouri, United States
Saint Luke's East - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Liberty Hospital
🇺🇸Liberty, Missouri, United States
Liberty Radiation Oncology Clinic
🇺🇸Liberty, Missouri, United States
Valley Medical Oncology Consultants-Fremont
🇺🇸Fremont, California, United States
Larry G Strieff MD Medical Corporation
🇺🇸Oakland, California, United States
Valley Care Health System - Pleasanton
🇺🇸Pleasanton, California, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
Evergreen Hematology and Oncology PS
🇺🇸Spokane, Washington, United States
Group Health Cooperative
🇺🇸Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Saint Luke's Episcopal Hospital
🇺🇸Houston, Texas, United States
Dekalb Medical Center
🇺🇸Decatur, Georgia, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Marin General Hospital
🇺🇸Greenbrae, California, United States
Sutter Health Western Division Cancer Research Group
🇺🇸Greenbrae, California, United States
Alta Bates Summit Medical Center - Summit Campus
🇺🇸Oakland, California, United States
Poudre Valley Hospital
🇺🇸Fort Collins, Colorado, United States
South Georgia Medical Center
🇺🇸Valdosta, Georgia, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Margaret R Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
Doctors Medical Center- JC Robinson Regional Cancer Center
🇺🇸San Pablo, California, United States
Gwinnett Medical Center
🇺🇸Lawrenceville, Georgia, United States