S0205 Gemcitabine With or Without Cetuximab as First-Line Therapy in Treating Patients With Locally Advanced Unresectable or Metastatic Adenocarcinoma of the Pancreas - Full Text View

Sponsor:	Southwest Oncology Group
Collaborators:	National Cancer Institute (NCI) Cancer and Leukemia Group B NCIC Clinical Trials Group
Information provided by:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00075686

Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as cetuximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether gemcitabine is more effective with or without cetuximab in treating pancreatic cancer.

PURPOSE: This randomized phase III trial is studying giving gemcitabine together with cetuximab to see how well it works compared to giving gemcitabine alone as first-line therapy in treating patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas.

Condition	Intervention	Phase
Pancreatic Cancer	Biological: cetuximab Drug: gemcitabine hydrochloride	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase III Randomized Open-Label Study Comparing Gemcitabine Plus Cetuximab (IMC-C225) Versus Gemcitabine As First-Line Therapy Of Patients With Advanced Pancreas Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Pancrelipase Gemcitabine Gemcitabine hydrochloride Cetuximab Ultrase

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Overall survival comparison between treatment groups [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate comparison between treatment groups as measured by RECIST and radiological evaluation at every other course [ Designated as safety issue: No ]
Time to treatment failure comparison between groups from registration to first observation of progressive disease, symptomatic deterioration, or death [ Designated as safety issue: No ]
Percentage of patients with EGFR tumor expression and compare overall survival of patients in the EGFR subset [ Designated as safety issue: No ]
Toxicity profile comparison of patients treated with 2 regimens and measured until 30 days after completion of study treatment [ Designated as safety issue: Yes ]
Total response rate comparison between treatment groups in the subset of patients with measurable disease by RECIST at every other course [ Designated as safety issue: No ]
Pain and quality of life comparison between treatment groups as measured by patient questionnaire at baseline, before each course, and then completion of study treatment [ Designated as safety issue: No ]

Estimated Enrollment:	704
Study Start Date:	January 2004

Arms	Assigned Interventions
Experimental: Gemcitabine + IMC-C225 Loading dose: Gemcitabine 1000mg/m2, IV on Day 1; Cetuxiumab 400mg/m2, IV on Day 1 (cycle 1 only) Weekly maintenance: Cetuximab 250mg/m2, IV on Days 8,15,22 of cycle 1 & days 1,8,15,22 of all subsequent cycles; Gemcitabine 1000mg/m2, IV on Days 8,15,22 of cycle 1 and Days 1,8,15 of all subsequent cycles.	Biological: cetuximab Loading dose: Cetuxiumab 400mg/m2, IV on Day 1 (cycle 1 only). Weekly maintenance: Cetuximab 250mg/m2, IV on Days 8,15,22 of cycle 1 & days 1,8,15,22 of all subsequent cycles Drug: gemcitabine hydrochloride 1000mg/m2 IV over 30 minutes
Experimental: Gemcitabine alone 1000mg/m2, IV on Days 1,8,15,22 of cycle 1 and Days 1,8,15 of all subsequent cycles.	Drug: gemcitabine hydrochloride 1000mg/m2 IV over 30 minutes

Detailed Description:

OBJECTIVES:

Compare the overall survival of patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas treated with gemcitabine and cetuximab vs gemcitabine alone.
Compare the time to treatment failure in patients treated with these regimens.
Estimate the percentage of patients with epidermal growth factor receptor (EGFR) tumor expression in patients treated with these regimens.
Compare the overall survival of patients in the EGFR-positive subset treated with these regimens.
Compare the toxicity of these regimens in these patients.
Compare the total response rate (confirmed and unconfirmed complete and partial response) in patients with measurable disease treated with these regimens.
Compare the patient report of pain and quality of life of patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to disease status (locally advanced unresectable vs metastatic), Zubrod performance status (0 or 1 vs 2), and prior pancreatectomy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22 and gemcitabine IV over 30 minutes on days 1, 8, 15, and 22 for course 1 and days 1, 8, and 15 for all subsequent courses.
Arm II: Patients receive gemcitabine as in arm I. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before each course, and at the end of study therapy.

Patients are followed every 6 months for 2 years and then annually for 1 year.

PROJECTED ACCRUAL: A total of 704 patients (352 per treatment arm) will be accrued for this study within 5 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically* or cytologically confirmed pancreatic adenocarcinoma meeting 1 of the following criteria:
- Locally advanced unresectable disease
- Distant metastatic disease NOTE: If diagnosis is based on a metastatic site the histology must be compatible with pancreatic cancer
Measurable or nonmeasurable disease by x-ray, scan, or physical examination
Tumor tissue must be submitted for evaluation of epidermal growth factor receptor expression before study entry
None of the following tumor types are allowed:
- Endocrine tumors
- Lymphoma of the pancreas
- Ampullary cancer
No known brain metastases

PATIENT CHARACTERISTICS:

Age

Not specified

Performance status

Zubrod 0-2

Life expectancy

At least 3 months

Hematopoietic

Absolute granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 2.0 times upper limit of normal (ULN)
SGOT or SGPT no greater than 2.5 times ULN

Renal

Creatinine no greater than 2.0 mg/dL

Cardiovascular

No significant history of cardiac disease
No uncontrolled hypertension
No unstable angina
No uncontrolled arrhythmia
No congestive heart failure

Other

Not pregnant or nursing
Fertile patients must use effective contraception
HIV negative
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior immunotherapy for advanced pancreatic cancer
No prior cetuximab or other therapy that targets the epidermal growth factor pathway
No prior chimerized or murine monoclonal antibody therapy
No other concurrent anticancer immunotherapy

Chemotherapy

At least 6 months since prior adjuvant chemotherapy
No prior chemotherapy or chemoradiotherapy for advanced pancreatic cancer
No prior gemcitabine
No other concurrent anticancer chemotherapy

Endocrine therapy

No prior hormonal therapy for advanced pancreatic cancer
No concurrent anticancer hormonal therapy

Radiotherapy

See Chemotherapy
At least 28 days since prior radiotherapy and recovered
Prior palliative radiotherapy to metastatic sites allowed
No concurrent anticancer radiotherapy, including whole brain radiotherapy for progressive disease (i.e., CNS metastasis)

Surgery

At least 14 days since prior pancreatic cancer surgery and recovered

Other

No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075686

Show 389 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Cancer and Leukemia Group B

NCIC Clinical Trials Group

Investigators

Study Chair:	Philip A. Philip, MD, PhD, FRCP	Barbara Ann Karmanos Cancer Institute
Study Chair:	Eileen O'Reilly, MD	Memorial Sloan-Kettering Cancer Center
Study Chair:	Ralph PW Wong, MD, FRCPC	CancerCare Manitoba

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

Philip PA, Benedetti J, Fenoglio-Preiser C, et al.: Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study. [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA4509, 2007.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, Rowland KM, Atkins JN, Mirtsching BC, Rivkin SE, Khorana AA, Goldman B, Fenoglio-Preiser CM, Abbruzzese JL, Blanke CD. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010 Aug 1;28(22):3605-10. Epub 2010 Jul 6.

Responsible Party:	Laurence H. Baker, DO, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00075686 History of Changes
Other Study ID Numbers:	CDR0000347414, SWOG-S0205, CALGB-S0205, CAN-NCIC-PAC1
Study First Received:	January 9, 2004
Last Updated:	July 13, 2011
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:

adenocarcinoma of the pancreas
stage III pancreatic cancer
stage IV pancreatic cancer

Additional relevant MeSH terms:

Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Pancrelipase
Gemcitabine
Cetuximab

Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on February 12, 2012