S0205 Gemcitabine w/ or w/o Cetuximab as First-Line Therapy in Locally Advanced Pancreas Cancer

This study has been completed.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00075686
First received: January 9, 2004
Last updated: April 4, 2012
Last verified: April 2012
  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 3

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:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Overall survival comparison between treatment groups [ Time Frame: every 4 weeks for 3 years ] [ 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 [ Time Frame: every 9 weeks until progression ] [ Designated as safety issue: No ]
  • Time to treatment failure comparison between groups from registration to first observation of progressive disease, symptomatic deterioration, or death [ Time Frame: every 4 weeks while on treatment ] [ Designated as safety issue: No ]
  • Percentage of patients with EGFR tumor expression and compare overall survival of patients in the EGFR subset [ Time Frame: every 4 weeks for 3 years ] [ Designated as safety issue: No ]
  • Toxicity profile comparison of patients treated with 2 regimens and measured until 30 days after completion of study treatment [ Time Frame: every 4 weeks while on 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 [ Time Frame: every 9 weeks until progression ] [ 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 [ Time Frame: every 4 weeks while on treatment ] [ Designated as safety issue: No ]

Enrollment: 766
Study Start Date: January 2004
Study Completion Date: April 2009
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
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
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:
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):
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00075686     History of Changes
Other Study ID Numbers: CDR0000347414, S0205, CALGB-S0205, CAN-NCIC-PAC1, U10CA032102
Study First Received: January 9, 2004
Last Updated: April 4, 2012
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:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
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 April 15, 2014