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

Multicenter Phase II Study of Short Course Radiotherapy Followed by Intensive Chemotherapy With Delayed Surgery for Rectal Cancer With Synchronous Distant Metastasis

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 Overview

• Status: Unknown
• Conditions: Rectal Cancer; Liver Metastasis; Lung Metastasis
• Intervention / Treatment: Radiation: Short Course Radiotherapy; Drug: Chemotherapy; Procedure: Delayed Surgery

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sun Mi Moon, MD, PhD; Phone Number: 82-2-970-1237; Email: msm386@yahoo.co.kr
• Study Contact Backup: Name: Won Il Jang, MD, MS; Phone Number: 82-2-970-1262; Email: zzang11@kirams.re.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 139-706
    • Recruiting
    • Korea Cancer Center Hospital
    • Contact: Sun Mi Moon, MD, PhD; Phone Number: 82-2-970-1237; Email: msm386@yahoo.co.kr
    • Contact: Won Il Jang, MD, MS; Phone Number: 82-2-970-1262; Email: zzang11@kirams.re.kr
    • Principal Investigator: Sun Mi Moon, MD, PhD
    • Sub-Investigator: Ui Sup Shin, MD, PhD
    • Sub-Investigator: Won Il Jang, MD, MS
    • Sub-Investigator: Sun Hee Ji, MD
  • Seoul, Korea, Republic of, 134-727
    • Active, not recruiting
    • Kyung Hee University Gangdong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: SCRT/ChemoTx with Delayed Surgery; Short course radiotherapy (25 Gy in 5 fractions) followed by intensive chemotherapy, compromising of FOLFOX of FOLFIRI (+-Bevacizumab or Cetuximab), with delayed surgery for rectal cancer with synchronous distant metastasis

Radiation: Short Course Radiotherapy; Radiotherapy to tumor and draining lymph node with 25 Gy in 5 fractions within 5 working days; Other Names: Upfront Short-Course Radiotherapy; Drug: Chemotherapy; 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); Other Names: FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab); Procedure: Delayed Surgery; 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).; Other Names: Total (or Tumor-specific) mesorectal excision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	R0 resection rate of primary and metastatic lesions	Expected average of 12 weeks (after resection)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	From the first date of radiotherapy to the date of death or last follow-up	2 years
Progression free survival rate	From the first date of radiotherapy to the date of first failure or last follow-up	2 years
Tumor regression grade	Tumor regression grade of primary lesion	Just after resection & pathologic report
Toxicity	Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	1 year

Collaborators and Investigators

• Sponsor: Korea Cancer Center Hospital
• Collaborators: Gachon University Gil Medical Center; The Catholic University of Korea; Gangnam Severance Hospital; Severance Hospital; Kyung Hee University Hospital at Gangdong; Pusan National University Yangsan Hospital; Chungnam National University Hospital; Wonju Severance Christian Hospital; Dongtan Sacred Heart Hospital; Catholic University of Korea, Yeouido St. Mary's Hospital; The Koreran Society of Coloproctology
• Investigators: Principal Investigator: Sun Mi Moon, MD, PhD, Korea Cancer Center Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: August 7, 2013
• First Submitted That Met QC Criteria: August 14, 2013
• First Posted (ESTIMATE): August 16, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Rectal cancer; Liver metastasis; Short course radiotherapy; Modified FOLFOX6; Delayed surgery; Synchronous metastasis; Lung metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Rectal Neoplasms; Neoplasms, Second Primary; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: K-1208-001-002 (OTHER: Korea Institute of Radiological and Medical Sciences IRB); KCT0000525 (REGISTRY: Clinical Research Information Service)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO