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

Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01923987
• Other study ID #: K-1208-001-002
• Secondary ID: KCT0000525K-1208
• Status: Recruiting
• Phase: Phase 2
• Start date: August 2012
• Est. completion date: December 2022

Study information

• Verified date: September 2019
• Source: Korea Cancer Center Hospital
• Contact: Sun Mi Moon, MD, PhD
• Phone: 82-2-970-1237
• Email: msm386[@]yahoo.co.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39
• Est. completion date: December 2022
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Liver Metastasis
• Lung Metastasis
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Rectal Cancer
• Rectal Neoplasms

Intervention

Radiation:
• Short Course Radiotherapy
Radiotherapy to tumor and draining lymph node with 25 Gy in 5 fractions within 5 working days

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)

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).

Locations

Country	Name	City	State
Korea, Republic of	Korea Cancer Center Hospital	Seoul
Korea, Republic of	Kyung Hee University Gangdong Hospital	Seoul

Sponsors (12)

Lead Sponsor

Collaborator

Korea Cancer Center Hospital

Catholic University of Korea, Seoul St. Mary`s Hospital, Catholic University of Korea, Yeouido St. Mary`s Hospital, Chungnam National University Hospital, Dongtan Sacred Heart Hospital, Gachon University Gil Medical Center, Gangnam Severance Hospital, Kyung Hee University Hospital at Gangdong, Pusan National University Yangsan Hospital, Severance Hospital, The Koreran Society of Coloproctology, Wonju Severance Christian Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R0 resection rate	R0 resection rate of primary and metastatic lesions	Expected average of 12 weeks (after resection)
Secondary	Overall survival rate	From the first date of radiotherapy to the date of death or last follow-up	2 years
Secondary	Progression free survival rate	From the first date of radiotherapy to the date of first failure or last follow-up	2 years
Secondary	Tumor regression grade	Tumor regression grade of primary lesion	Just after resection & pathologic report
Secondary	Toxicity	Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	1 year