Short Course Radiotherapy Followed Intensive Chemotherapy With Delayed Surgery for Rectal Cancer With Synchronous Distant Metastasis

Phase 2UnknownNCT01923987

Korea Cancer Center Hospital39 enrolled

Overview

Radical treatment of primary rectal cancer with synchronous distant metastases includes surgical resection of primary and metastatic lesion. However, primary rectal cancer in case of metastasized disease are often locally advanced disease and need downsizing before surgery. It is reported that pelvic recurrence rates and distant metastasis rates outside liver are 30\~35% and 60%, respectively. Therefore, combined treatment with radiotherapy and chemotherapy is used. However, the sequence of treatment modalities is not yet definitely established and preoperative chemoradiotherapy and surgical resection is accepted as an option of treatment. Conventional long course chemoradiotherapy delays administration of full-dose chemotherapy, and metastatic lesion can be progressed during chemoradiotherapy. In present study, we evaluate the efficacy of short course radiotherapy (SCRT) followed by full-dose chemotherapy with delayed surgical resection of the primary tumor and metastases.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Rectal Cancer Liver Metastasis Lung Metastasis

Interventions

Short Course RadiotherapyRADIATION

Radiotherapy to tumor and draining lymph node with 25 Gy in 5 fractions within 5 working days

ChemotherapyDRUG

* Oxaliplatin 85 mg/m2 IV over 2 hrs on Day 1 * Irinotecan 180 mg/m2 IV over 30-90 mins on Day 1 * Leucovorin 400 mg/m2 IV over 2 hrs on Day 1 and 2 * 5-fluorouracil bolus 400 mg/m2 IV push on Day 1 and 2 (or 5-fluorouracil infusion 600 mg/m2 IV continuous infusion over 22 hrs). * Bevacizumab 5 mg/kg IV over 90 mins on Day 1 * Cetuximab (only for patients with K-ras wild type and positive EGFR mutation) 400 mg/m2 IV over 2 hrs on Day 1, and 250 mg/m2 IV over 1 hr on Day 8, 15, 22, 29, and 36. * FOLFOX or FOLFIRI (+-Bevacizumab ) repeats every 14 days for up to 3 courses. Cetuximab repeats every week for up to 6 courses * Postoperative FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab) for up to 9 cycles (total 12 cycles)

Delayed SurgeryPROCEDURE

If primary tumor and metastases is resectable after FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab) of 3 cycles, patients have surgical resection (and/or radiofrequency ablation to metastases).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Pathologically confirmed adenocarcinoma of rectum * Lower margin of tumor within 12 cm from anal verge * Clinically locally advanced (T3-4 or N1-2) disease * Potentially resectable and synchronous distant metastases in liver and/or lung. The resectability of metastatic lesions is determined by size, number, location, general condition, liver function, and lung function. * Over 18 years * Eastern Cooperative Oncology Group performance status 0-2 * Proper organ function (Hemoglobin ≥ 10 g/dl, Absolute neutrophil count (ANC) ≥ 1,500/mm3, Platelet ≥ 100,000/mm3, Creatinine ≤ 1.5 mg/dl, Clearance of creatinine \>50 ml/min using Cockcroft-Gault formula, Bilirubin ≤ 1.5 x upper limit of normal (ULN), Liver enzyme (Aspartate aminotransferase/Alanine transaminase/Alkaline phosphatase) ≤ 2.5 x ULN) * Subject who should sign on the informed consent form before participate the trial. Exclusion Criteria: * Metastases in other organ except liver or lung * History of other type of malignancies within 3 years other than non-melanoma of the skin or carcinoma in situ of cervix * Hereditary colorectal cancer (FAP, HNPCC, and etc) * Bowel obstruction or impending bowel obstruction * Uncontrolled severe illness, unsuitable to chemoradiotherapy (within 6 months, myocardial infarct, unstable angina, heart failure, uncontrolled arrhythmia, uncontrolled epilepsy, central nervous system disease, psychological disorder, and etc) * Subject pregnant or breast feeding, or incapable of appropriate contraception * Unresected synchronous colorectal cancer * History of prior pelvic radiotherapy * History of prior chemotherapy for colorectal cancer * Great surgery within 4 week before study enrollment * Participant in other trial within 4 week before study enrollment

Outcomes

Primary Outcomes

R0 resection rate

R0 resection rate of primary and metastatic lesions

Time frame: Expected average of 12 weeks (after resection)

Secondary Outcomes

Overall survival rate

From the first date of radiotherapy to the date of death or last follow-up

Time frame: 2 years

Progression free survival rate

From the first date of radiotherapy to the date of first failure or last follow-up

Time frame: 2 years

Tumor regression grade

Tumor regression grade of primary lesion

Time frame: Just after resection & pathologic report

Toxicity

Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Time frame: 1 year