Know Cancer

forgot password

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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Stage IV Pancreatic Cancer

Thank you

Trial Information

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


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

After completion of study treatment, patients are followed every 6 months for up to 3 years.

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended phase II dose of cixutumumab when given in combination with gemcitabine hydrochloride and erlotinib hydrochloride (Phase I)

Outcome Description:

Toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE V3.0).

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Philip Philip

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

March 2008

Completion Date:

Related Keywords:

  • Stage IV Pancreatic Cancer
  • Pancreatic Neoplasms



Baylor College of Medicine Houston, Texas  77030
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Medical University of South Carolina Charleston, South Carolina  29425-0721
University of Washington Medical Center Seattle, Washington  98195-6043
Sinai Hospital of Baltimore Baltimore, Maryland  21225
Glendale Memorial Hospital and Health Center Glendale, California  91204
Sutter Health Western Division Cancer Research Group Greenbrae, California  94904
South Georgia Medical Center Valdosta, Georgia  31603
Akron General Medical Center Akron, Ohio  44302
University of Texas Medical Branch Galveston, Texas  77555-1329
LDS Hospital Salt Lake City, Utah  84143
Boston Medical Center Boston, Massachusetts  02118
William Beaumont Hospital Royal Oak, Michigan  48073
Carolinas Medical Center Charlotte, North Carolina  28232-2861
Scott and White Memorial Hospital Temple, Texas  76508
Group Health Cooperative Seattle, Washington  98112
Great Falls Clinic Great Falls, Montana  59405
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109
Munson Medical Center Traverse City, Michigan  49684
Northern Rockies Radiation Oncology Center Billings, Montana  59101
Bozeman Deaconess Hospital Bozeman, Montana  59715
Kalispell Medical Oncology Kalispell, Montana  59901
Kalispell Regional Medical Center Kalispell, Montana  59901
American Fork Hospital American Fork, Utah  84003
Logan Regional Hospital Logan, Utah  84321
McKay-Dee Hospital Center Ogden, Utah  84403
Harborview Medical Center Seattle, Washington  98104
Cancer Care Northwest - Spokane South Spokane, Washington  99202
Welch Cancer Center Sheridan, Wyoming  82801
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
City of Hope Medical Center Duarte, California  91010
Alta Bates Summit Medical Center - Summit Campus Oakland, California  94609
Sutter Solano Medical Center Vallejo, California  94589
Poudre Valley Hospital Fort Collins, Colorado  80524
Saint Joseph's Hospital of Atlanta Atlanta, Georgia  30342-1701
Piedmont Hospital Atlanta, Georgia  30309
Gwinnett Medical Center Lawrenceville, Georgia  30045
Southern Regional Medical Center Riverdale, Georgia  30274-2600
Mecosta County Medical Center Big Rapids, Michigan  49307
Highland General Hospital Oakland, California  94602
Randolph Hospital Asheboro, North Carolina  27203
Crossroads Cancer Center Effingham, Illinois  62401
Menorah Medical Center Overland Park, Kansas  66209
Shawnee Mission Medical Center Shawnee Mission, Kansas  66204
North Kansas City Hospital Kansas City, Missouri  64116
Research Medical Center Kansas City, Missouri  64132
Saint Luke's East - Lee's Summit Lee's Summit, Missouri  64086
Liberty Hospital Liberty, Missouri  64068
Heartland Regional Medical Center Saint Joseph, Missouri  64506
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
Northern Montana Hospital Havre, Montana  59501
Wenatchee Valley Medical Center Wenatchee, Washington  98801-2028
Rocky Mountain Oncology Casper, Wyoming  82609
Ben Taub General Hospital Houston, Texas  77030
Methodist Hospital Houston, Texas  77030
Presbyterian Hospital Charlotte, North Carolina  28233-3549
Metro Health Hospital Grand Rapids, Michigan  49506
Guardian Oncology and Center for Wellness Missoula, Montana  59804
East Bay Radiation Oncology Center Castro Valley, California  94546
Contra Costa Regional Medical Center Martinez, California  94553-3156
Larry G Strieff MD Medical Corporation Oakland, California  94609
Saint Louis University Hospital St. Louis, Missouri  63110-0250
University of Rochester Rochester, New York  14642
El Camino Hospital Mountain View, California  94040
Wayne State University Detroit, Michigan  48202
California Pacific Medical Center San Francisco, California  94115
Montana Cancer Consortium CCOP Billings, Montana  59101
Decatur Memorial Hospital Decatur, Illinois  62526
Montana Cancer Specialists Missoula, Montana  59807-7877
Memorial Health University Medical Center Savannah, Georgia  31404
University of Southern California Los Angeles, California  90033
DeKalb Medical Center Decatur, Georgia  30033
University of Cincinnati Cincinnati, Ohio  45267-0502
Northside Hospital Atlanta, Georgia  30342
Mills - Peninsula Hospitals Burlingame, California  94010
Valley Medical Oncology Consultants-Castro Valley Castro Valley, California  94546
Eden Hospital Medical Center Castro Valley, California  94546
Valley Medical Oncology Consultants-Fremont Fremont, California  94538
Bay Area Breast Surgeons Inc Oakland, California  94609
Bay Area Tumor Institution CCOP Oakland, California  94609
Tom K Lee Inc Oakland, California  94609
Valley Medical Oncology Consultants Pleasanton, California  94588
Valley Care Health System - Pleasanton Pleasanton, California  94588
Doctors Medical Center- JC Robinson Regional Cancer Center San Pablo, California  94806
Atlanta Regional CCOP Atlanta, Georgia  30342
Well Star Cobb Hospital Austell, Georgia  30106
John B Amos Cancer Center Columbus, Georgia  31904
Wellstar Kennestone Hospital Marietta, Georgia  30060
Saint Joseph's-Candler Health System Savannah, Georgia  31405
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Mercy Health Partners-Mercy Campus Muskegon, Michigan  49443
Saint Luke's Cancer Institute Kansas City, Missouri  64111
Saint Luke's Hospital of Kansas City Kansas City, Missouri  64111
Saint Joseph Health Center Kansas City, Missouri  64114
Liberty Radiation Oncology Clinic Kansas City, Missouri  64116
Truman Medical Center Kansas City, Missouri  64108
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment Center Butte, Montana  59701
Benefis Healthcare- Sletten Cancer Institute Great Falls, Montana  59405
Berdeaux, Donald MD (UIA Investigator) Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Glacier Oncology PLLC Kalispell, Montana  59901
Community Medical Hospital Missoula, Montana  59801
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Interlakes Foundation Inc-Rochester Rochester, New York  14623
Highland Hospital Rochester, New York  14620
Wayne Memorial Hospital Goldsboro, North Carolina  27534
Margaret R Pardee Memorial Hospital Hendersonville, North Carolina  28791
The Don and Sybil Harrington Cancer Center Amarillo, Texas  79106
Veterans Administration Medical Center Houston, Texas  77030
Saint Luke's Episcopal Hospital Houston, Texas  77030
Harrison Bremerton Hematology and Oncology Bremerton, Washington  98310
Columbia Basin Hematology and Oncology PLLC Kennewick, Washington  99336
Minor and James Medical PLLC Seattle, Washington  98104
The Polyclinic Seattle, Washington  98122
Swedish Medical Center-First Hill Seattle, Washington  98122-4307
University of California Medical Center At Irvine-Orange Campus Orange, California  92868
Marin General Hospital Greenbrae, California  94904
Harbin Clinic Medical Oncology and Clinical Research Rome, Georgia  30165
Moses Cone Health System-Regional Cancer Center Greensboro, North Carolina  27403
Annie Penn Memorial Hospital Reidsville, North Carolina  27320
Sandra L Maxwell Cancer Center Cedar City, Utah  84720
Intermountain Medical Center Murray, Utah  84157
Utah Valley Regional Medical Center Provo, Utah  84603
Dixie Medical Center Regional Cancer Center Saint George, Utah  84770
Intermountain Health Care Salt Lake City, Utah  84103
Utah Cancer Specialists-Salt Lake City Salt Lake City, Utah  84106
Skagit Valley Hospital Mt. Vernon, Washington  98273
Evergreen Hematology and Oncology PS Spokane, Washington  99218
Saint Luke's South Hospital Overland Park, Kansas  66213
Heartland Hematology and Oncology Associates Incorporated Kansas City, Missouri  64118
Saint Joseph Oncology Inc Saint Joseph, Missouri  64507
Arnot Ogden Medical Center Elmira, New York  14905
Memorial Hospital Of Martinsville Martinsville, Virginia  24115
Cancer Care Center of Decatur Decatur, Illinois  62526
Alta Bates Summit Medical Center-Herrick Campus Berkeley, California  94704
PeaceHealth Saint Joseph Medical Center Bellingham, Washington  98225
Bronson Battle Creek Battle Creek, Michigan  49017
NEA Baptist Memorial Hospital Jonesboro, Arkansas  72401
Harrison Poulsbo Hematology and Oncology Poulsbo, Washington  98370
Christus Saint Frances Cabrini Hospital Alexandria, Louisiana  71301
Veterans Administration Medical Center - Cincinnati Cincinnati, Ohio  45220