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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Andrew S. Kraft, MD, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00408564
First received: December 6, 2006
Last updated: June 17, 2013
Last verified: June 2013
  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: oxaliplatin
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Progression-free survival at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Overall survival and progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Response duration in patients with at least partial response to treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • survial behaviors [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: January 2006
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine,Oxaliplatin and Cetuximab
Gemcitabine will be given on day 1 of every 2 week cycle. Oxaliplatin will be given day 2 of every 2 week cycle. Cetuximab will be given every week for 12 weeks.
Biological: cetuximab Drug: oxaliplatin Drug: Gemcitabine
Experimental: Radiation and capecitabine
Daily radiation and capceitabine Monday-Friday for a total of 5 and a half weeks.
Drug: capecitabine Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
No publications provided

Responsible Party: Andrew S. Kraft, MD, Director, Hollings Cancer Center, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00408564     History of Changes
Other Study ID Numbers: CDR0000518313, MUSC-100918, BMS-MUSC-100918, SANOFI-MUSC-100918
Study First Received: December 6, 2006
Last Updated: June 17, 2013
Health Authority: United States: Federal Government

Keywords provided by Medical University of South Carolina:
adenocarcinoma of the pancreas
stage II pancreatic cancer
stage III 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
Gemcitabine
Capecitabine
Fluorouracil
Oxaliplatin
Cetuximab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 01, 2014