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

Primary Purpose

Rectal Cancer, Liver Metastasis, Lung Metastasis

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Short Course Radiotherapy

Chemotherapy

Delayed Surgery

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Short course radiotherapy, Modified FOLFOX6, Delayed surgery, Rectal cancer, Synchronous metastasis, Liver metastasis, Lung metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Kyung Hee University Gangdong Hospital
Korea Cancer Center HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SCRT/ChemoTx with Delayed Surgery

Arm Description

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

Outcomes

Primary Outcome Measures

R0 resection rate

R0 resection rate of primary and metastatic lesions

Secondary Outcome Measures

Overall survival rate

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

Progression free survival rate

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

Tumor regression grade

Tumor regression grade of primary lesion

Toxicity

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

Full Information

NCT ID

NCT01923987

First Posted

August 7, 2013

Last Updated

September 18, 2019

Sponsor

Korea Cancer Center Hospital

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01923987

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Unknown status

Study Start Date

August 2012 (undefined)

Primary Completion Date

December 2020 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Korea Cancer Center Hospital

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Cancer, Liver Metastasis, Lung Metastasis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

SCRT/ChemoTx with Delayed Surgery

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Short Course Radiotherapy

Other Intervention Name(s)

Upfront Short-Course Radiotherapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Chemotherapy

Other Intervention Name(s)

FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab)

Intervention Description

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

Procedure

Intervention Name(s)

Delayed Surgery

Other Intervention Name(s)

Total (or Tumor-specific) mesorectal excision

Intervention Description

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).

Primary Outcome Measure Information:

Title

R0 resection rate

Description

R0 resection rate of primary and metastatic lesions

Time Frame

Expected average of 12 weeks (after resection)

Secondary Outcome Measure Information:

Title

Overall survival rate

Description

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

Time Frame

2 years

Title

Progression free survival rate

Description

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

Time Frame

2 years

Title

Tumor regression grade

Description

Tumor regression grade of primary lesion

Time Frame

Just after resection & pathologic report

Title

Toxicity

Description

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

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sun Mi Moon, MD, PhD

Phone

82-2-970-1237

msm386@yahoo.co.kr

First Name & Middle Initial & Last Name or Official Title & Degree

Won Il Jang, MD, MS

Phone

82-2-970-1262

zzang11@kirams.re.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sun Mi Moon, MD, PhD

Organizational Affiliation

Korea Cancer Center Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Kyung Hee University Gangdong Hospital

City

Seoul

ZIP/Postal Code

134-727

Country

Korea, Republic of

Individual Site Status

Active, not recruiting

Facility Name

Korea Cancer Center Hospital

City

Seoul

ZIP/Postal Code

139-706

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sun Mi Moon, MD, PhD

Phone

82-2-970-1237

msm386@yahoo.co.kr

First Name & Middle Initial & Last Name & Degree

Won Il Jang, MD, MS

Phone

82-2-970-1262

zzang11@kirams.re.kr

First Name & Middle Initial & Last Name & Degree

Sun Mi Moon, MD, PhD

First Name & Middle Initial & Last Name & Degree

Ui Sup Shin, MD, PhD

First Name & Middle Initial & Last Name & Degree

Won Il Jang, MD, MS

First Name & Middle Initial & Last Name & Degree

Sun Hee Ji, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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