Preoperative Chemoradiation Followed by Chemotherapy for Locally Advanced Rectal Cancer (PREPARE)

National Cancer Center (NCC)

Status and phase: Unknown; Phase 2

Conditions: Adenocarcinoma; Rectal Neoplasms

Treatments: Radiation: pelvic radiation capecitabine 5-fluorouracil; Drug: Capecitabine Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT01952951

KCSG CO14-03

Details and patient eligibility

About

The current standard treatment of locally advanced rectal cancer (clinical stage II or III) is preoperative radiation with chemotherapy (CRT) followed by surgery. But this approach can be suboptimal for patients with high risk features (more deeply-seated tumor or many regional lymph nodes involved)that are associated with recurrence. This study test a hypothesis that CRT followed by chemotherapy before surgery can improve efficacy of preoperative treatment.

Full description

Downstaging rate with CRT using fluoropyrimidine monotherapy is usually 30-40%.In MRI-defined high-risk patients, downstaging rate with conventional fluoropyrimidine-based monotherapy with radiation has not been shown. We assume that the downstaging rate of chemoradiation arm (control arm) would be 30%, and that addition of CapOx after CRT (experimental arm) may increase downstaging rate 30% to 50%. A sample size of 52 patients per group is needed have 85% power to detect downstaging rate = 50% as compared to 30% with type I error rate of 15%. We will perform one interim futility analysis when half of the patients are recruited and evaluated for the primary endpoint. O'Brien-Fleming boundary will be considered. Therefore, when 26 patients per arm are evaluated, the interim futility analysis will be performed, and when the Z score at the interim is less than -0.09192 (one-sided p-value greater than 0.5366192), the study will be stopped for futility. Considering 5% follow-up loss, a sample size of 55 per arm (a total of 110 patients) will be studied.

Enrollment: 110 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• histologically confirmed adenocarcinoma of the rectum

• distal margin of tumor located from 0 to 12 cm from anal verge measured by digital rectal examination

• high risk clinical stage II or III in MRI (satisfying at least one of the followings)

  • circumferential resection margin < 1 mm involved
  • low-lying tumor below anal verge 3 cm
  • T3 > 5 mm extramural spread
  • T4 (involving surrounding structures or peritoneum)
  • cN2 (4 or more mixed signal intensity or irregularly bordered node or tumor deposit)

• age 20 years or more

• ECOG (Eastern Cooperative Oncology Group) performance status 0-2

• No prior chemotherapy, radiotherapy to pelvis

• Adequate bone marrow function

• Adequate renal function

• Adequate hepatic function

• patients must sign the informed consent indicating that they were aware of the investigational nature of the study in keeping with the policy of the hospital

Exclusion criteria

• malignant disease of the rectum other than adenocarcinoma or arisen from chronic inflammatory bowel disease
• any unresected synchronous colon cancer
• any distant metastases
• intestinal obstruction or impending obstruction, but decompressing colostomy is permitted
• any previous or concurrent malignancy withih 5 years other than non-melanoma skin cancer / in situ cancer of uterine cervix / early gastric cancer / thyroid cancer of low risk
• any other morbidity or situation with relative contraindication for chemoradiotherapy
• patients with history of significant gastric or small bowel resection, or malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may compromise the absorption of capecitabine
• pregnant or lactating women or patients of childbearing potential not predicting adequate contraception

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

chemoradiation followed by CapOx

Experimental group

Description:

preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by 2 cycles of chemotherapy (Capecitabine Oxaliplatin - CapOx) and surgery (total mesorectal excision)

Treatment:

Drug: Capecitabine Oxaliplatin

Radiation: pelvic radiation capecitabine 5-fluorouracil

chemoradiation

Active Comparator group

Description:

preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by rest for 8 weeks and surgery (total mesorectal excision)

Treatment:

Radiation: pelvic radiation capecitabine 5-fluorouracil