Preoperative CRT With Temozolomide Plus Capecitabine in Rectal Cancer
Condition: Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: Temozolomide
Intervention description: Preoperative chemoradiotherapy with fixed dose of capecitabine and temozolomide, the dose of temozolomide will be escalated for finding MTD and RD.
Intervention MeSH terms: Capecitabine; Temozolomide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Temozolomide; capecitabine; rectal cancer

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.
    

Eligibility 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.