Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00682786
First received: April 11, 2008
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

Determine if genotype-directed neoadjuvant chemoradiation, using information from the thymidylate synthase promoter polymorphism, result in a greater degree of tumor downstaging in high risk patients compared to historical controls.


Condition Intervention Phase
Rectal Carcinoma
Drug: 5FU
Radiation: Radiation
Procedure: Surgery of resectable lesions
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Rate of Tumor Downstaging Compared With Historical Controls. [ Time Frame: 1 year after enrollment ] [ Designated as safety issue: No ]

    Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1.

    Historical studies demonstrate a DS rate of 45%.



Secondary Outcome Measures:
  • Complete Response Rates [ Time Frame: 1 year after enrollment ] [ Designated as safety issue: No ]

    Complete tumor response is defined as the absence of any viable tumor in the rectum (ypT0).

    Pathologic complete response (pCR) is defined as the absence of any viable tumor in the rectum or in the perirectal lymph nodes (ypT0N0).

    pCR rate of historical controls is 8%-14%.


  • Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation. [ Time Frame: Prior to start of study treatment and 3-6 weeks post completion of radiation therapy ] [ Designated as safety issue: No ]
    The questionnaire is encouraged but not required.

  • Determine Patient Fears and Expectations of Pharmacogenetics. [ Time Frame: Prior to start of study treatment and 3-6 weeks post completion of radiation therapy ] [ Designated as safety issue: No ]
    The questionnaire is encouraged but not required.


Enrollment: 135
Study Start Date: October 2002
Study Completion Date: August 2010
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)

Radiation 45 Gy in 25 fractions to the pelvis.

5FU CIVI 225 mg/m2/day by CIVI during radiation

Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.

Drug: 5FU
Other Names:
  • Fluorouracil
  • 5-fluorouracil
Radiation: Radiation Procedure: Surgery of resectable lesions
Experimental: Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)

Radiation 45 Gy in 25 fractions to the pelvis.

5FU CIVI 225 mg/m2/day by CIVI during radiation

Irinotecan 50 mg/m2 IV weekly for 5 doses.

Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.

Drug: 5FU
Other Names:
  • Fluorouracil
  • 5-fluorouracil
Radiation: Radiation Procedure: Surgery of resectable lesions Drug: Irinotecan
Other Name: Camptosar

  Eligibility

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

Inclusion Criteria:

  • Biopsy proven adenocarcinoma of the rectum
  • Lesion evaluated by surgeon and found to be resectable
  • Stage T3 or T4 disease on radiography or ultrasound
  • Karnofsky Performance Status at >60
  • Laboratory criteria:

    • Absolute neutrophil count >= 1.5 K
    • Platelets >= 100 K
    • Total Bilirubin <= 2.0;
    • SGOT and Alkaline Phosphatase <= 2 x upper limit of normal
    • Creatinine < 2.0
  • Informed consent signed
  • Patients with distant metastatic disease will be eligible if they satisfy all other conditions.

Exclusion Criteria:

  • Pregnant women, children < 18 years, or patients unable to give informed consent
  • Patients with a past history of pelvic radiotherapy.
  • Patients with prior malignancy in the past 5 years except: skin cancer or in-situ cervical cancer. However, patients with synchronous adenocarcinomas are eligible provided either (a) the synchronous adenocarcinoma was in a removed pedunculated polyp and did not invade the stalk or (b) the synchronous adenocarcinoma was in a removed polyp that lay within the surgical field (extent of resection would not be changed) or (c) the synchronous adenocarcinoma is smaller than the index rectal cancer and lies completely within the radiation field (clinically favorable second lesion and the extend of radiation and surgery would not be changed).
  • Patients with known allergy to 5-fluorouracil or irinotecan
  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: NCT00682786

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Benjamin Tan, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00682786     History of Changes
Other Study ID Numbers: 02-0561
Study First Received: April 11, 2008
Results First Received: July 14, 2014
Last Updated: September 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
rectal
rectum
cancer
carcinoma

Additional relevant MeSH terms:
Carcinoma
Rectal Neoplasms
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
Irinotecan
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014