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

Stage IV Pancreatic Cancer Clinical Trial

Official title:

A Phase I and Randomized Phase II Trial of Gemcitabine + Erlotinib (NSC-718781) + IMC-A12 (NSC-742460) vs. Gemcitabine + Erlotinib as First-Line Treatment in Patients With Metastatic Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00617708
• Other study ID #: NCI-2009-00797
• Secondary ID: NCI-2009-00797CD
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2008
• Est. completion date: February 25, 2014

Study information

• Verified date: January 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: February 25, 2014
• Est. primary completion date: September 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Related Conditions & MeSH terms

• Pancreatic Neoplasms
• Stage IV Pancreatic Cancer

Intervention

Biological:
• cixutumumab
Given IV

Drug:
• erlotinib hydrochloride
Given PO
• gemcitabine hydrochloride
Given IV

Locations

Country	Name	City	State
United States	Akron General Medical Center	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Christus Saint Frances Cabrini Hospital	Alexandria	Louisiana
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	American Fork Hospital	American Fork	Utah
United States	Randolph Hospital	Asheboro	North Carolina
United States	Atlanta Regional CCOP	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	Well Star Cobb Hospital	Austell	Georgia
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana
United States	Montana Cancer Consortium CCOP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Boston Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison Bremerton Hematology and Oncology	Bremerton	Washington
United States	Mills - Peninsula Hospitals	Burlingame	California
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Veterans Administration Medical Center - Cincinnati	Cincinnati	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Dekalb Medical Center	Decatur	Georgia
United States	Wayne State University	Detroit	Michigan
United States	City of Hope Medical Center	Duarte	California
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Arnot Ogden Medical Center	Elmira	New York
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Glendale Memorial Hospital and Health Center	Glendale	California
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Saint Mary's Health Care	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Marin General Hospital	Greenbrae	California
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Northern Montana Hospital	Havre	Montana
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	Saint Luke's Episcopal Hospital	Houston	Texas
United States	Veterans Administration Medical Center	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	NEA Baptist Memorial Hospital	Jonesboro	Arkansas
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	Columbia Basin Hematology and Oncology PLLC	Kennewick	Washington
United States	Gwinnett Medical Center	Lawrenceville	Georgia
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	Logan Regional Hospital	Logan	Utah
United States	University of Southern California	Los Angeles	California
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Memorial Hospital Of Martinsville	Martinsville	Virginia
United States	Community Medical Hospital	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	El Camino Hospital	Mountain View	California
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Partners-Mercy Campus	Muskegon	Michigan
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Breast Surgeons Inc	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of California Medical Center At Irvine-Orange Campus	Orange	California
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Harrison Poulsbo Hematology and Oncology	Poulsbo	Washington
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Highland Hospital	Rochester	New York
United States	Interlakes Foundation Inc-Rochester	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Intermountain Health Care	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	California Pacific Medical Center	San Francisco	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Saint Joseph's-Candler Health System	Savannah	Georgia
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	Group Health Cooperative	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	The Polyclinic	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Munson Medical Center	Traverse City	Michigan
United States	South Georgia Medical Center	Valdosta	Georgia
United States	Sutter Solano Medical Center	Vallejo	California
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose Determination	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).	28 days
Primary	Progression-Free Survival	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.	Up to 3 years
Secondary	Overall Survival	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.	Up to 3 years
Secondary	Response	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.	Up to 3 years
Secondary	Toxicity	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.	Up to 3 years