Cetuximab, Gemcitabine, and Oxaliplatin Followed By Surgery or External-Beam Radiation Therapy and Capecitabine in Treating Patients With Locally Advanced, Nonmetastatic Pancreatic Cancer That Cannot Be Removed By Surgery - Full Text View

Sponsored by:	Medical University of South Carolina
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00408564

Purpose

RATIONALE: Monoclonal antibodies, such as cetuximab, 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. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cetuximab together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Giving cetuximab and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with oxaliplatin and gemcitabine followed by surgery or external-beam radiation therapy and capecitabine works in treating patients with locally advanced, nonmetastatic pancreatic cancer that cannot be removed by surgery.

Condition	Intervention	Phase
Pancreatic Cancer	Biological: cetuximab Drug: capecitabine Drug: gemcitabine hydrochloride Drug: oxaliplatin Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Study of Neoadjuvant Gemcitabine/Oxaliplatin and Cetuximab Followed by Surgery or Concurrent External Beam Radiation With Capecitabine for Patients With Locally Advanced Unresectable Nonmetastatic Pancreatic Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer Radiation Therapy Surgery

Drug Information available for: Oxaliplatin Gemcitabine Gemcitabine hydrochloride Capecitabine Cetuximab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Tolerability [ Designated as safety issue: Yes ]
Overall survival and progression-free survival [ Designated as safety issue: No ]
Response rate [ Designated as safety issue: No ]
Response duration in patients with at least partial response to treatment [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	January 2006
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the progression-free survival rate in patients with unresectable, locally advanced, nonmetastatic adenocarcinoma of the pancreas treated with neoadjuvant therapy comprising cetuximab, gemcitabine hydrochloride, and oxaliplatin followed by either surgery or chemoradiotherapy comprising external-beam radiotherapy and capecitabine.

Secondary

Determine the toxicity and tolerability of this regimen in these patients.
Determine overall survival and progression-free survival.
Determine the response rate in these patients.
Determine the response duration (defined as the time from first observation response to the time of progressive disease) in patients who achieve at least a partial response to treatment.
Determine the biomarker response of CA19-9.

OUTLINE: This is an open-label study.

Neoadjuvant therapy: Patients receive cetuximab IV over 1-2 hours on days 1 and 8, gemcitabine hydrochloride IV over 100 minutes on day 1, and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated after completion of neoadjuvant therapy. Patients with metastatic disease are taken off study. Beginning within 4 weeks after completion of neoadjuvant therapy, patients with resectable disease proceed to surgical resection or chemoradiotherapy (by choice); patients with unresectable disease proceed to chemoradiotherapy.
Surgery: Patients undergo surgical resection with the Whipple procedure.
Chemoradiotherapy: Patients receive oral capecitabine twice daily 5 days a week (on days 1-5) and undergo external-beam radiotherapy once daily 5 days a week for 5½ weeks. After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or radiologically confirmed pancreatic cancer, meeting both of the following criteria:
- Locally advanced, nonmetastatic disease
- Surgically unresectable disease
Measurable disease, defined as unidimensionally measurable by physical exam or imaging study
- The following are considered nonmeasurable disease:
  - Bone-only disease
  - Pleural or peritoneal effusions
  - CNS lesions
  - Irradiated lesions in the absence of progression after radiotherapy
No history or evidence of CNS disease
No metastatic disease to distant organs (e.g., liver, lung, brain, or bone)

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 2.0 mg/dL
Creatinine ≤ 2.0 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 90 days after completion of study therapy
No acute hepatitis
No known HIV positivity
No active or uncontrolled infection
No significant history of uncontrolled cardiac disease, including, but not limited to, any of the following:
- Uncontrolled hypertension
- Unstable angina
- Myocardial infarction within the past 6 months
- Uncontrolled congestive heart failure
- Cardiomyopathy with decreased ejection fraction
No prior severe infusion reaction to a monoclonal antibody
No active second malignancy other than nonmelanoma skin cancer
No history of deep vein thrombosis
No history of bleeding diathesis or coagulopathy
No other severe concurrent disease, mental incapacitation, or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

No prior therapy for pancreatic cancer
No prior therapy specifically targeting the epidermal growth factor-receptor pathway
No major surgical procedure or open biopsy within the past 28 days
No prior radiotherapy or chemotherapy
No prior or concurrent full-dose anticoagulants or thrombolytics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00408564

Locations

United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

Investigators

Principal Investigator:

Andrew S. Kraft, MD

Medical University of South Carolina

More Information

Additional Information:

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

No publications provided

Responsible Party:	Hollings Cancer Center at Medical University of South Carolina ( Andrew S. Kraft )
Study ID Numbers:	CDR0000518313, MUSC-100918, BMS-MUSC-100918, SANOFI-MUSC-100918
Study First Received:	December 6, 2006
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00408564 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
Capecitabine
Digestive System Neoplasms
Immunologic Factors
Pancreatic Neoplasms
Cetuximab
Endocrine System Diseases
Immunosuppressive Agents
Antiviral Agents

Pancrelipase
Oxaliplatin
Digestive System Diseases
Radiation-Sensitizing Agents
Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Adenocarcinoma
Gemcitabine
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Oxaliplatin
Neoplasms by Site
Therapeutic Uses
Gemcitabine
Endocrine Gland Neoplasms

Capecitabine
Digestive System Neoplasms
Cetuximab
Endocrine System Diseases
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Pancreatic Diseases

ClinicalTrials.gov processed this record on September 01, 2009