Neoadjuvant Cetuximab, Fluorouracil, and Pelvic Irradiation in Treating Patients With Locally Advanced or Locally Recurrent Rectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00084773
First received: June 10, 2004
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy such as fluorouracil work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab with fluorouracil and radiation therapy may kill more tumor cells.


Condition Intervention
Colorectal Cancer
Biological: cetuximab
Drug: fluorouracil
Procedure: neoadjuvant therapy
Radiation: radiation therapy

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Clinical Trial of Preoperative Cetuximab With Concurrent Continuous Infusion Fluorouracil and Pelvic Radiation in Patients With Local-Regionally Advanced Rectal Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Safety profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Activity in terms of pathological complete response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: March 2004
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab, Fluorouracil, and Pelvic Irradiation

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 and fluorouracil IV continuously on days 1-42. Patients undergo whole-pelvic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Treatment continues in the absence of disease progression or unacceptable toxicity.

Approximately 1-3 weeks after completion of study treatment, patients undergo surgical resection followed by adjuvant chemotherapy off-study.

Patients are followed for up to 5 years.

Biological: cetuximab Drug: fluorouracil Procedure: neoadjuvant therapy Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety profile of neoadjuvant cetuximab, fluorouracil, and pelvic irradiation in patients with locally advanced or locally recurrent rectal cancer.

Secondary

  • Determine the activity of this regimen, in terms of pathological complete response rate, in these patients.

OUTLINE: This is a non-randomized, open-label, pilot study.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 and fluorouracil IV continuously on days 1-42. Patients undergo whole-pelvic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Treatment continues in the absence of disease progression or unacceptable toxicity.

Approximately 1-3 weeks after completion of study treatment, patients undergo surgical resection followed by adjuvant chemotherapy off-study.

Patients are followed for up to 5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed rectal adenocarcinoma meeting 1 of the following staging criteria:

    • Locally advanced disease

      • Resectable (uT3) disease

        • Primary gross transmural tumor that is not adherent to adjacent pelvic structures by endorectal ultrasound
      • Primary tethered or unresectable (cT4 or uT4) disease

        • Primary tumor is contiguous with or adherent or fixed to adjacent pelvic structures by clinical exam and CT scan
        • Primary surgery would likely leave residual tumor
      • Small volume extrapelvic metastases allowed
    • Recurrent disease after definitive resection

      • Disease limited to the pelvis
  • Requires combined modality treatment
  • Epidermal growth factor receptor status-positive, -negative, or -unknown
  • If previously treated with adjuvant fluorouracil-based chemotherapy, no disease recurrence during or within 12 months after completion of adjuvant therapy

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0 -1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hemoglobin > 8.0 g/dL
  • Platelet count > 150,000/mm^3

Hepatic

  • Not specified

Renal

  • Creatinine ≤ 1.5 times upper limit of normal

Cardiovascular

  • No myocardial infarction within the past 6 months
  • No evidence of uncontrolled congestive heart failure requiring therapy

Other

  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No known severe hypersensitivity to cetuximab or any of its excipients
  • No uncontrolled infection
  • No high-grade bowel obstruction (bowel lumen ≤ 1 cm) unless patient has undergone protective surgical diversion or endoscopic stenting procedure
  • No other concurrent medical or psychiatric condition or disease that would preclude study participation
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3 months after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior cetuximab
  • No prior murine or chimeric monoclonal antibody therapy
  • No prior biological response modifiers for metastatic colorectal cancer
  • No concurrent anti-vascular endothelial growth factor/Flk-1 monoclonal antibody therapy
  • No other concurrent antibody therapy or immunotherapy
  • No concurrent gene therapy
  • No concurrent vaccine therapy
  • No concurrent angiogenesis inhibitors, including thalidomide

Chemotherapy

  • See Disease Characteristics
  • No prior chemotherapy for metastatic colorectal cancer
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent hormonal therapy

Radiotherapy

  • No prior radiotherapy for metastatic colorectal cancer
  • No prior pelvic radiotherapy
  • No other concurrent radiotherapy

Surgery

  • See Disease Characteristics
  • Fully recovered from prior oncologic or other major surgery

Other

  • No other prior therapy that targets the epidermal growth factor receptor pathway
  • No other concurrent experimental therapy or drugs
  • No concurrent matrix metalloprotease inhibitors
  • No concurrent participation in another clinical study
  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: NCT00084773

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Leonard B. Saltz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00084773     History of Changes
Other Study ID Numbers: 04-006, MSKCC-04006
Study First Received: June 10, 2004
Last Updated: March 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
recurrent rectal cancer
stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Cetuximab
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014