Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy Followed by Surgery in Treating Patients With Locally Advanced Cancer of the Rectum

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00006094
First received: August 3, 2000
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

Drugs used in chemotherapy use 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. Combining chemotherapy, radiation therapy, and surgery may be a more effective treatment for cancer of the rectum. Phase II trial to study the effectiveness of combining oxaliplatin, fluorouracil, and external-beam radiation therapy followed by surgery in treating patients who have locally advanced cancer of the rectum


Condition Intervention Phase
Adenocarcinoma of the Rectum
Stage II Rectal Cancer
Stage III Rectal Cancer
Drug: oxaliplatin
Drug: fluorouracil
Radiation: external beam radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Preoperative Oxaliplatin (NSC# 266046), 5-Fluorouracil, and External Beam Radiation Therapy in Locally Advanced Rectal Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The maximum tolerated dose of oxaliplatin when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinomas [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: From protocol entry until documented progression of disease or death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method.

  • Pathological complete response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The new regimen will be considered worthy of further investigation if 5 or greater CR's are observed among the 25 patients treated at the MTD. Assuming the new regimen will result in a 30% CR rate, the probability of observing 5 or greater CR's in 25 patients studied is 0.91. For an underlying CR rate of 0.25 this probability is 0.79. The probability of observing 5 or greater CR's if the underlying CR rate is 0.10 is 0.10.

  • Latent toxicities graded using the Common Toxicity Criteria (CTC) version 2.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: July 2000
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (oxaliplatin, fluorouracil, EBRT)
Patients receive oxaliplatin IV over 1 hour on day 1, fluorouracil IV continuously on days 1-7, and radiotherapy on days 1-5. Treatment repeats weekly for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of oxaliplatin when combined with fluorouracil and external beam radiotherapy in patients with locally advanced adenocarcinoma of the rectum.

(Phase I closed to accrual effective 03/27/2003). II. Determine the pathological response rate in patients treated with this preoperative regimen and surgical resection.

III.Determine the late toxicity of this preoperative regimen in these patients. IV. Determine, in a preliminary manner, the progression-free survival, local control, and overall survival in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study of oxaliplatin.

Patients receive oxaliplatin IV over 1 hour on day 1, fluorouracil IV continuously on days 1-7, and radiotherapy on days 1-5. Treatment repeats weekly for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at that dose level in the phase II portion of the study. (Phase I closed to accrual effective 03/27/2003). Patients may undergo radical resection of rectal tumor within 4-6 weeks after completion of chemoradiotherapy.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for phase I of the study (phase I closed to accrual effective 03/27/2003) and a total of 19 patients will be accrued for phase II of the study within 12-18 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically proven previously untreated adenocarcinoma of the rectum thatbegins within 12 cm of the anal verge by sigmoidoscopy and/or colonoscopy

    • Locally advanced disease defined as any of the following:

      • Fixed or immovable tumor on physical exam
      • T4 disease with invasion of adjacent structures (e.g., pelvic sidewall, sacral pelvis, bladder, or prostate) by CT scan, rectal ultrasound, or MRI
      • T3 disease with invasion through the wall of the muscularis propria by transrectal ultrasound, CT scan, or MRI
  • No distant metastatic disease
  • Performance status - ECOG 0-2
  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than upper limit of normal (ULN)
  • SGOT/SGPT no greater than 2.5 times ULN
  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance at least 60 mL/min
  • No active second malignancy except nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • Patients are not considered to have an active second malignancy if they have completed therapy and are at less than 30% risk of relapse
  • No prior or concurrent evidence of neuropathy
  • No history of allergy to platinum compounds or antiemetics
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No prior fluorouracil or platinum-based therapy for any malignancy
  • No other concurrent chemotherapy
  • Hormonal therapy allowed only for non-disease related conditions (e.g., insulin for diabetes) OR intermittently as an antiemetic (e.g., dexamethasone)
  • No prior pelvic irradiation
  • No concurrent antiretroviral therapy (HAART) for HIV positive patients
  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: NCT00006094

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: David Ryan Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006094     History of Changes
Other Study ID Numbers: NCI-2012-02357, CALGB-89901, U10CA031946, CDR0000068099
Study First Received: August 3, 2000
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
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 31, 2014