Preoperative CRT With or Without Induction Chemotherapy for Rectal Cancer With Liver Metastases

NCT ID: NCT01643070

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2015-12-31

Brief Summary

To investigate the feasibility of preoperative chemoradiation with oxaliplatin plus capecitabine, with or without prior induction chemotherapy in patients with locally advanced or marginally resectable rectal cancer with resectable synchronous liver metastases.

Detailed Description

Preoperative chemoradiation is now an initial treatment of choice for locally advanced resectable rectal cancer, and 5-fluorouracil is the standard agent during chemoradiation. Capecitabine is an oral fluoropyrimidine which has been thought to be a replacement for intravenous 5-fluorouracil, and several trials have proved that preoperative chemoradiation with capecitabine was also effective in this setting.

Oxaliplatin, a newer platinum agent, plus fluoropyrimidines (either 5-fluorouracil or capecitabine) is one of the standard cytotoxic chemotherapeutic regimen for metastatic colorectal cancer, and it is also proved to be effective as neoadjuvant chemotherapy for patients with liver only metastasis from colorectal cancer.

Approximately 25% of patients with colorectal cancer have liver metastases initially at the time of diagnosis and there have been quite well established evidences for clear survival benefits from hepatic metastasectomy in these patients. Treatment for colorectal liver metastases should be planned with consideration of both systemic chemotherapy and local treatment modality (surgery or radiofrequency ablation) because long term survival would be expected after curative liver metastasectomy. As mentioned previously, neoadjuvant oxaliplatin plus fluoropyrimidines before hepatic metastasectomy improved disease-free survival, thus it is thought to be that better systemic controls would be achieved with perioperative oxaliplatin based chemotherapy.

In patients with locally advanced rectal cancer, preoperative chemoradiation with fluoropyrimidines improves local control but not systemic control. Recent randomized trials of preoperative chemoradiation with oxaliplatin plus fluoropyrimidines failed to show better local control rates than those with fluoropyrimidines alone. But it is too early to determine the non-superiority of preoperative chemoradiation with oxaliplatin plus fluoropyrimidines in terms of systemic control; long-term duration of follow-up is needed to determine the efficacy in terms of disease-free or overall survival and it is evident that oxaliplatin based chemotherapy is effective for systemic control in patients who will be candidate for liver metastasectomy.

Thus, the investigators planned a randomized phase II trial of preoperative chemoradiation with oxaliplatin plus capecitabine, with or without prior induction chemotherapy in patients with locally advanced or borderlinely resectable rectal cancer with resectable synchronous liver metastases.

Conditions

Rectal Cancer; Liver Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

XELOX RT

Concurrent XELOX-RT (Capecitabine, Oxaliplatin, radiotherapy)

Group Type: ACTIVE_COMPARATOR

Capecitabine, Oxaliplatin

Intervention Type: DRUG

Induction chemotherapy - Induction XELOX (Capecitabine 1250 mg/m2 PO twice daily on D1-14 and oxaliplatin 130 mg/m2 on D1, every 3 weeks for 2 cycles) Preoperative chemoradiotherapy - XELOX RT (Capecitabine 825 mg/m2 PO twice daily during radiotherapy and oxaliplatin 50 mg/m2/day on weekly.)

Radiotherapy

Intervention Type: RADIATION

Preoperative radiotherapy, 5040 cGy with 28 fractions

Induction XELOX

Induction XELOX(Capecitabine, Oxaliplatin) followed by XELOX-RT (Capecitabine, Oxaliplatin, radiotherapy)

Group Type: ACTIVE_COMPARATOR

Capecitabine, Oxaliplatin

Intervention Type: DRUG

Induction chemotherapy - Induction XELOX (Capecitabine 1250 mg/m2 PO twice daily on D1-14 and oxaliplatin 130 mg/m2 on D1, every 3 weeks for 2 cycles) Preoperative chemoradiotherapy - XELOX RT (Capecitabine 825 mg/m2 PO twice daily during radiotherapy and oxaliplatin 50 mg/m2/day on weekly.)

Radiotherapy

Intervention Type: RADIATION

Preoperative radiotherapy, 5040 cGy with 28 fractions

Interventions

Capecitabine, Oxaliplatin

Induction chemotherapy - Induction XELOX (Capecitabine 1250 mg/m2 PO twice daily on D1-14 and oxaliplatin 130 mg/m2 on D1, every 3 weeks for 2 cycles) Preoperative chemoradiotherapy - XELOX RT (Capecitabine 825 mg/m2 PO twice daily during radiotherapy and oxaliplatin 50 mg/m2/day on weekly.)

Intervention Type: DRUG

Radiotherapy

Preoperative radiotherapy, 5040 cGy with 28 fractions

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed adenocarcinoma of the rectum Tumor located within 12 cm from anal verge Clinical stage of T3-4 or N+ by rectal MRI ± endorectal ultrasound Age over 18 years No prior systemic treatment or radiation Adequate major organ functions Borderline resectability of primary rectal cancer Complete resectability of liver metastases (measurable by RECIST 1.1)

Exclusion Criteria

• Unresectable liver metastases (6 or more metastatic lesions, major vessel invasion)
• Extrahepatic metastasis

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Tae Won Kim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tae Won Kim, Professor

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

Asan Medical Center

Seoul, Songpa, South Korea

Countries

South Korea

Other Identifiers

XELOX-RT

Identifier Type: -

Identifier Source: org_study_id