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

Rectal Cancer Clinical Trial

Official title:

Randomized Phase II Trial of Preoperative Chemoradiation With or Without Induction Chemotherapy In Patients With Locally Advanced Or Borderlinely Resectable Rectal Cancer With Resectable Synchronous Liver Metastases

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01643070
• Other study ID #: XELOX-RT
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 1, 2011
• Last updated: January 11, 2016
• Start date: January 2010
• Est. completion date: December 2016

Study information

• Verified date: January 2016
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 38
• Est. completion date: December 2016
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis
• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Capecitabine, Oxaliplatin
Induction chemotherapy - 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 - Capecitabine 825 mg/m2 PO twice daily during radiotherapy and oxaliplatin 50 mg/m2/day on weekly.

Radiation:
• Radiotherapy
Preoperative radiotherapy, 5040 cGy with 28 fractions

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul	Songpa

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R0 resection rate after simultaneous surgery of the rectum and the liver		1 day	No