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

NCT ID: NCT01923987

Last Updated: 2019-09-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2022-12-31

Brief 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.

Conditions

Rectal Cancer; Liver Metastasis; Lung Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Short Course Radiotherapy

Intervention Type: RADIATION

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

Chemotherapy

Intervention Type: DRUG

• 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 Surgery

Intervention Type: PROCEDURE

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).

Interventions

Short Course Radiotherapy

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

Intervention Type: RADIATION

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)

Intervention Type: DRUG

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).

Intervention Type: PROCEDURE

Other Intervention Names

Upfront Short-Course Radiotherapy; FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab); Total (or Tumor-specific) mesorectal excision

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyung Hee University Hospital at Gangdong

OTHER

Sponsor Role: collaborator

Gachon University Gil Medical Center

OTHER

Sponsor Role: collaborator

Catholic University of Korea, Yeouido St. Mary's Hospital

UNKNOWN

Sponsor Role: collaborator

Pusan National University Yangsan Hospital

OTHER

Sponsor Role: collaborator

Gangnam Severance Hospital

OTHER

Sponsor Role: collaborator

Severance Hospital

OTHER

Sponsor Role: collaborator

Wonju Severance Christian Hospital

OTHER

Sponsor Role: collaborator

Chungnam National University Hospital

OTHER

Sponsor Role: collaborator

Dongtan Sacred Heart Hospital

OTHER

Sponsor Role: collaborator

The Koreran Society of Coloproctology

UNKNOWN

Sponsor Role: collaborator

The Catholic University of Korea

OTHER

Sponsor Role: collaborator

Korea Cancer Center Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sun Mi Moon

Korea Cancer Center Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sun Mi Moon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Korea Cancer Center Hospital

Locations

Kyung Hee University Gangdong Hospital

Seoul, , South Korea

Site Status: ACTIVE_NOT_RECRUITING

Korea Cancer Center Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Sun Mi Moon, MD, PhD

Role: CONTACT

msm386@yahoo.co.kr

82-2-970-1237

Won Il Jang, MD, MS

Role: CONTACT

zzang11@kirams.re.kr

82-2-970-1262

Facility Contacts

Sun Mi Moon, MD, PhD

Role: primary

msm386@yahoo.co.kr

82-2-970-1237

Won Il Jang, MD, MS

Role: backup

zzang11@kirams.re.kr

82-2-970-1262

Other Identifiers

KCT0000525

Identifier Type: REGISTRY

Identifier Source: secondary_id

K-1208-001-002

Identifier Type: OTHER

Identifier Source: secondary_id

K-1208-001-002

Identifier Type: -

Identifier Source: org_study_id