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: July 22, 2013
Last verified: July 2013

April 11, 2008
July 22, 2013
October 2002
December 2008   (final data collection date for primary outcome measure)
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. [ Time Frame: 1 year after enrollment ] [ Designated as safety issue: No ]
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. [ Time Frame: throughout trial participation ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00682786 on ClinicalTrials.gov Archive Site
  • Demonstrate objective response rates in high risk patients which are equal to or better than historic controls. [ Time Frame: 1 year after enrollment ] [ Designated as safety issue: No ]
  • 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.
  • Discover additional genetic variants which predict for downstaging of rectal cancer after chemoradiation. [ Time Frame: Prior to start of study treatment ] [ Designated as safety issue: No ]
  • Demonstrate objective response rates in high risk patients which are equal to or better than historic controls. [ Time Frame: throughout trial participation ] [ Designated as safety issue: No ]
  • Define patient quality of life prior to and following neoadjuvant chemoradiation. [ Time Frame: throughout trial participation ] [ Designated as safety issue: No ]
  • Determine patient fears and expectations of pharmacogenetics. [ Time Frame: throughout trial participation ] [ Designated as safety issue: No ]
  • Discover additional genetic variants which predict for downstaging of rectal cancer after chemoradiation. [ Time Frame: throughout trial participation ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma
Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Rectal Carcinoma
  • Drug: 5FU
    Other Names:
    • Fluorouracil
    • 5-fluorouracil
  • Radiation: Radiation
  • Procedure: Surgery of resectable lesions
  • Drug: Irinotecan
    Other Name: Camptosar
  • Experimental: Arm 1 (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.

    Interventions:
    • Drug: 5FU
    • Radiation: Radiation
    • Procedure: Surgery of resectable lesions
  • Experimental: Arm 2 (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.

    Interventions:
    • Drug: 5FU
    • Radiation: Radiation
    • Procedure: Surgery of resectable lesions
    • Drug: Irinotecan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
135
August 2010
December 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00682786
02-0561
Yes
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Benjamin Tan, M.D. Washington University School of Medicine
Washington University School of Medicine
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP