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

NCT01923987 | Unknown Phase 2

• 2 other identifiers: K-1208-001-002KCT0000525
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

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

Keywords

Short course radiotherapy; Modified FOLFOX6; Delayed surgery; Rectal cancer; Synchronous metastasis; Liver metastasis; Lung metastasis

Outcome Measures

Primary Outcomes (1)

• R0 resection rate

  R0 resection rate of primary and metastatic lesions

  Expected average of 12 weeks (after resection)

Secondary Outcomes (4)

• Overall survival rate

  2 years

• Progression free survival rate

  2 years

• Tumor regression grade

  Just after resection & pathologic report

• Toxicity

  1 year

Study Arms (1)

SCRT/ChemoTx with Delayed Surgery

EXPERIMENTAL

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; Drug: Chemotherapy; Procedure: Delayed Surgery

Interventions

Short Course Radiotherapy RADIATION

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

Also known as: Upfront Short-Course Radiotherapy

SCRT/ChemoTx with Delayed Surgery

Chemotherapy 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)

Also known as: FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab)

SCRT/ChemoTx with Delayed Surgery

Delayed Surgery 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).

Also known as: Total (or Tumor-specific) mesorectal excision

SCRT/ChemoTx with Delayed Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Kyung Hee University Gangdong Hospital

Seoul, 134-727, South Korea

ACTIVE NOT RECRUITING

Korea Cancer Center Hospital

Seoul, 139-706, South Korea

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Drug Therapy; Folfox protocol; Bevacizumab; Cetuximab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sun Mi Moon, MD, PhD

  Korea Cancer Center Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sun Mi Moon, MD, PhD

CONTACT

82-2-970-1237; msm386@yahoo.co.kr

Won Il Jang, MD, MS

CONTACT

82-2-970-1262; zzang11@kirams.re.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Korea Cancer Center Hospital

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 16, 2013
• Study Start: August 1, 2012
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: September 20, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)