Induction Cetuximab (IM-C225), Gemcitabine, and Oxaliplatin in Pancreatic Cancer Patients - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center Bristol-Myers Squibb
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00338039

Purpose

Primary Objective:

1. To evaluate the efficacy of a combination of cetuximab with systemic chemotherapy followed by chemoradiation in locally advanced pancreatic cancer. 2. The primary endpoint is actuarial one year survival.

Secondary Objectives:

To evaluate the local tumor response in patients treated with the above regimen.
To characterize the safety of the above regimen.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: Cetuximab Drug: Gemcitabine Drug: Oxaliplatin Drug: Capecitabine Radiation: Radiotherapy	Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine hydrochloride Gemcitabine Capecitabine Oxaliplatin Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial of Induction Cetuximab (IM-C225), Gemcitabine and Oxaliplatin, Followed by Radiotherapy With Concurrent Capecitabine, and Cetuximab, Followed by Maintenance Cetuximab and Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

To learn if the drug cetuximab (C225, Erbitux) combined with chemotherapy (gemcitabine and oxaliplatin) followed by radiation therapy given with chemotherapy (capecitabine) and cetuximab will help to control pancreatic cancer [ Time Frame: 3 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The safety of this combination treatment will also be studied [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	69
Study Start Date:	September 2005
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Systemic chemotherapy followed by chemoradiation in locally advanced pancreatic cancer.	Drug: Cetuximab 400 mg/m^2 IV day #1, then 250 mg/m^2/week +/-1 day continued throughout induction chemotherapy, chemoradiation and maintenance chemotherapy. Drug: Gemcitabine Induction Therapy: 1 gm/m^2 over 100 minutes every 2 weeks +/-1 day for 4 doses. Chemotherapy Maintenance: 1 gm/m^2/week over 100 minutes weekly for 3 weeks then 1 week off. Drug: Oxaliplatin Induction Chemotherapy: 100 mg/m^2 over 120 min. every 2 weeks +/-1 day for 4 doses. Drug: Capecitabine Chemoradiation (to start 2-3 weeks post completion of oxaliplatin and gemcitabine): 825 mg/m^2 PO twice daily Monday-Friday throughout radiation. Radiation: Radiotherapy Conformal radiation therapy to gross disease, total dose = 50.4 Gy delivered in 28 fractions.

Arms

Assigned Interventions

1: Experimental

Systemic chemotherapy followed by chemoradiation in locally advanced pancreatic cancer.

Drug: Cetuximab

400 mg/m^2 IV day #1, then 250 mg/m^2/week +/-1 day continued throughout induction chemotherapy, chemoradiation and maintenance chemotherapy.

Drug: Gemcitabine

Induction Therapy: 1 gm/m^2 over 100 minutes every 2 weeks +/-1 day for 4 doses.

Chemotherapy Maintenance: 1 gm/m^2/week over 100 minutes weekly for 3 weeks then 1 week off.

Drug: Oxaliplatin

Induction Chemotherapy: 100 mg/m^2 over 120 min. every 2 weeks +/-1 day for 4 doses.

Drug: Capecitabine

Chemoradiation (to start 2-3 weeks post completion of oxaliplatin and gemcitabine): 825 mg/m^2 PO twice daily Monday-Friday throughout radiation.

Radiation: Radiotherapy

Conformal radiation therapy to gross disease, total dose = 50.4 Gy delivered in 28 fractions.

Detailed Description:

Cetuximab is a drug that blocks epidermal growth factor receptor (EGFR). EGFR may be involved in certain types of cancer. When EGFR is stimulated, a series of chemical reactions starts that results in a tumor being "told" to grow. Cetuximab tries to stop these reactions by blocking EGFR. This may stop tumors from growing. Cetuximab has been shown to increase the effect of chemotherapy and of radiation therapy, both of which will also be given in this study.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam. Blood (about 2 tablespoons) and urine will be collected for routine tests. Chest x-rays and computed tomography (CT) scans of the abdomen will be done. Women who are able to have children must have a negative urine pregnancy test.

If you are found to be eligible to take part in this study, you will first receive cetuximab every 2 weeks for 8 weeks (4 doses). Cetuximab will be given every 2 weeks throughout the duration of the study. Cetuximab will be continued during the radiation and capecitabine combination, during the retesting stage and then during the chemotherapy that is given after radiation therapy. Cetuximab infusions will be given over approximately 2 hours. Gemcitabine and oxaliplatin chemotherapy will be given once every 2 weeks (4 doses) for 8 weeks. Both drugs are given through a central line and over about 2 hours. Cetuximab will be given first, followed by gemcitabine, and then followed by oxaliplatin. A CT scan and chest X-ray will be done 2 weeks after the last dose (at Week 10).

As long as the tumor has not grown or spread, you will then receive cetuximab, capecitabine, and radiation therapy together. The Capecitabine will be given by mouth twice a day every day of radiation therapy (5 and 1/2 weeks). Radiation therapy will be given once a day for 5 days in a row. It will be given for 5 and 1/2 weeks or 28 treatments. The radiation will be given from 4 directions and focused on the tumor while you are lying on your back. You will continue to receive cetuximab by vein once every 2 weeks during capecitabine and radiation therapy.

After radiotherapy, you will continue to take cetuximab by vein every 2 weeks. The effect of treatment will be evaluated 5-6 weeks after the completion of radiation therapy and capecitabine. A chest x-ray and CT scans will be performed, and about 2 tablespoons of blood will be drawn for routine testing. As long as the tumor has not grown or spread and the side effects are not too severe, you may continue to receive Cetuximab by vein once every 2 weeks . You will also receive Gemcitabine by vein in the same dose as before for 3 out of every 4 weeks as long as the tumor does not grow and the side effects are not too severe. CT scans and chest x-rays will then be done every 2 months to evaluate the status of the tumor.

During the study, you will have physical exams, including weekly blood tests (about 2 tablespoons) each. The possible development of side effects will be closely monitored and could require extra blood and/or urine samples.

You will be taken off study if your disease gets worse or intolerable side effects occur. You may have surgery if at any time during therapy the tumor can be removed surgically. A separate consent form will be used for that situation.

This is an investigational study. Capecitabine, oxaliplatin, and cetuximab are approved by the FDA for colon cancer but have not been approved by the FDA for pancreatic cancer. Gemcitabine is approved for metastatic pancreatic cancer. Up to 69 patients will take part in this multicenter study. Up to 50 will be enrolled at M. D. Anderson.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Cytologic or histologic proof of adenocarcinoma of the pancreas is required prior to treatment. Patients can have tumor originating in any part of the pancreas. Islet cell tumors are not eligible. Only patients with non- metastatic, unresectable disease (AJCC 2002 stage T4 NX M0) are eligible. CT findings of lung, liver, peritoneal metastasis are equivocal, are eligible. Patients who cannot undergo resection because of underlying medical problems are also eligible. Diagnosis of Pancreatic Adenocarcinoma by bile duce brushings are acceptable. Patients with regional nodal disease are eligible.
All patients must be staged with a physical exam, CXR, and contrast-enhanced helical thin-cut abdominal CT. Unresectability is defined by CT criteria: a) evidence of tumor extension to the celiac axis or superior mesenteric (SM) artery, or b) evidence on either CT or angiogram of occlusion of the SM vein or SM/ portal vein confluence. If a tumor does not meet this definition and is found to be unresectable at surgical exploration, then that tumor is considered unresectable.
Patients must be 18 years and older. There will be no upper age restriction
Karnofsky performance status greater than or equal to 70 are eligible.
Patients must either be not of child bearing potential or have a negative urine pregnancy test within 72 hours of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or they have been postmenopausal for at least 12 months.
Women of childbearing potential must agree to practice adequate contraception and to refrain from breast-feeding, as specified in the informed consent. Sexually active males must practice contraception during the study.
Bone marrow function: absolute neutrophil count (ANC) >1,500/ul. Platelets >100,000/ul.
Renal function: creatinine clearance > 30 mL/min (calculated with Cockcroft-Gault equation).
Hepatic function: total bilirubin less than 5mg/dL. if the patient required an endobiliary stent, the bilirubin level must have declined on consecutive measurements indicating adequate biliary decompression; alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal.
Neurologic function: neuropathy (sensory) < CTC Grade 2.
Patients must sign a study-specific consent form, which is attached to this protocol.

Exclusion Criteria:

Patients with a history of prior metastatic cancer.
Patients must not have significant infection, i.e., requiring IV antibiotics, or other coexistent medical condition that would preclude protocol therapy.
Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with ejection fraction less than < 30%.
Prior therapy which specifically and directly targets the EGFR pathway.
Prior severe infusion reaction (bronchospasm, stridor, urticaria and/or hypotension) to a monoclonal antibody.
Any prior history of radiotherapy to the abdomen.
History or evidence upon physical examination of CNS disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)
Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil.
Patients who have had an organ allograft.
Patients on Coumadin must be changed to Lovenox at least 1 week prior to starting capecitabine. Low dose (1 mg) Coumadin is allowed.
Patients taking Sorivudine or Brivudine A must be off of these drugs for 4 weeks prior to starting capecitabine. Patients taking cimetidine must have this drug discontinued. Ranitidine or a drug from another anti-ulcer class can be substituted for cimetidine if necessary.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00338039

Contacts

Contact: Christopher H. Crane, MD

713-563-2300

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Christopher H. Crane, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Bristol-Myers Squibb

Investigators

Principal Investigator:

Christopher H. Crane, MD

U.T.M.D. Anderson Cancer Center

More Information

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Christopher H. Crane, MD/Associate Professor )
Study ID Numbers:	2004-0983
Study First Received:	January 27, 2006
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00338039
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Pancreatic Cancer
Cetuximab
C225
Erbitux

Gemcitabine
Oxaliplatin
Capecitabine

Study placed in the following topic categories:

Oxaliplatin
Capecitabine
Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Cetuximab

Endocrine System Diseases
Pancreatic Diseases
Gastrointestinal Neoplasms
Endocrinopathy
Gemcitabine
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 14, 2009