Preoperative CRT With Temozolomide Plus Capecitabine in Rectal Cancer

• Status: Completed
• Trial end date: 2016-05-04
• Target enrollment: 0
• Participant gender: All

Summary

The investigators planned a phase I study of preoperative CRT with capecitabine plus temozolomide inpatients with locally advanced resectable rectal cancer: 1) the role of temozolomide as a radiosensitizer has been well established, 2) hypermethylation (or low expression) of MGMT promoter is associated with colorectal carcinogenesis, can be found in 20~40% of colorectal cancer patients, and this proportion could be adequate for validation as its role of predictive biomarker, and 3) temozolomide can be additive or synergistic because radiotherapy is now essential in the treatment of rectal cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Treatments: Capecitabine; Dacarbazine; Temozolomide

Criteria

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the rectum

• Tumor located within 12cm of anal verge

• Clinical stage of T3-4 or N+ by rectal MRI with or without endorectal ultrasound

• Available tumor samples before study treatment (fresh or paraffin-embedded) for immunohistochemistry (IHC) and methylation-specific PCR (MSP) to investigate MGMT expression and hypermethylation

• Male or female aged over 20 years

• Be ambulatory and have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• No prior systemic treatment (chemotherapy, immunotherapy) or radiation therapy

• Adequate major organ functions as following:

• Be willing and able to comply with the protocol for the duration of the study.

• Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

Exclusion Criteria:

• Histology other than adenocarcinoma or tumor arising from inflammatory bowel disease

• Inadequate tumor sample for MGMT IHC or MSP

• Any evidence of systemic metastasis

• Unresected synchronous colon cancer

• Intestinal obstructions or impending intestinal obstruction, but bypass surgery (colostomy or ileostomy) is permitted before study treatment

• Uncontrolled or severe cardiovascular disease

• Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.

• Other malignancy within the past 5 years except cured non-melanomatous skin cancer, carcinoma in situ of the cervix, or thyroid papillary carcinoma.

• Organ allografts requiring immunosuppressive therapy.

• Psychiatric disorder or uncontrolled seizure that would preclude compliance.

• Pregnant, nursing women or patients with reproductive potential without contraception.

• Patients receiving a concomitant treatment with drugs interacting with 5-FU such as flucytosine, phenytoin, or warfarin et al.

• Known dihydropyrimidine dehydrogenase (DPD) deficiency.

• Known hypersensitivity to any of the components of the study medications.