Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

The Washington University

Status and phase: Completed; Phase 2

Conditions: Rectal Carcinoma

Treatments: Radiation: Radiation; Procedure: Surgery of resectable lesions; Drug: 5FU; Drug: Irinotecan

Study type: Interventional

Funder types: Other

Identifiers

NCT00682786

02-0561

Details and patient eligibility

About

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.

Enrollment: 135 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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135 participants in 2 patient groups

Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)

Experimental group

Description:

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.

Treatment:

Drug: 5FU

Procedure: Surgery of resectable lesions

Radiation: Radiation

Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)

Experimental group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: 5FU

Procedure: Surgery of resectable lesions

Radiation: Radiation