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Preoperative Hyperfractionated Radiotherapy or Radiochemotherapy in Locally Advanced Rectal Cancer.

Primary Purpose

Rectal Cancer

Status

Unknown status

Phase

Phase 3

Locations

Poland

Study Type

Interventional

Intervention

Hyperfractionated Radiochemotherapy

Hyperfractionated Radiotherapy

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Rectal neoplasm, Preoperative hyperfractionated radiotherapy, Preoperative hyperfractionated radiochemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Karnofsky Index 80% or better (Zubrod 0-1)
Histological proved diagnosis of rectal cancer (adeno- or mucinous carcinoma)
Primary rectal cancer:
3.1. Maximum 12 cm above dentate line (upper limit) 3.2. Staged T2N+ or T3N0 or T3N+ (by endorectal ultrasound or Computed Tomography [CT]/Magnetic Resonance Imaging [MRI] scan)
No evidence of metastatic disease as determined by chest X-ray and abdominal ultrasound (or CT-scan of chest and abdomen or other investigations such as Positron Emission Tomography [PET] scan or biopsy if required)
Adequate bone marrow function with platelets more than 100 × 10^9/l and neutrophils more than 2.0 × 10^9/l
Creatinine clearance more than 50 ml/min
Serum bilirubin less than 2.0 × Upper Limit of institutional Normal range (ULN)
Written informed consent is obtained prior to commencement of trial treatment (confirmed the signature on the consent form for the proposed project and the standard medical consent form for radiotherapy within the abdominal cavity).

Exclusion Criteria:

Rectal cancer other than adeno- or mucinous carcinoma
Previous or concurrent malignancies, with the exception of adequately treated basal cell carcinoma of the skin
Patients with locally advanced inoperable disease, such as T4-tumour
Presence of metastatic disease or recurrent rectal tumour
Any previous chemotherapy or radiotherapy, and any investigational treatment for rectal cancer
Concurrent uncontrolled medical conditions
Pregnancy or breast feeding
Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease) or myocardial infarction within the last six months
Evidence of hereditary colorectal cancer (Hereditary Non-Polyposis Colorectal Cancer [HNPCC] and Familial Adenomatous Polyposis [FAP])
Medical or psychiatric conditions that compromise the patient's ability to give informed consent
No agreement for randomisation

Sites / Locations

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice BranchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hyperfractionated Radiochemotherapy

Hyperfractionated Radiotherapy

Arm Description

radiotherapy in rectal tumor area due to the placing of pelvic nodal groups to a total dose of 42 Gy, 1.5 Gy d fx 2 times a day; (gap between the factions min. 6-8h) - duration of treatment 2.5 weeks with simultaneous two cycles of chemotherapy according to the scheme: 5FU-325mg/m2 (bolus) on 1-3 and 16-18 (last 3 days of radiotherapy). Surgical resection has to be done within 14 days or 5-6 weeks after the completion of hyperfractionated radiochemotherapy (HRTCT).

Outcomes

Primary Outcome Measures

• The rate of patients with downstaging after radiotherapy or radiochemotherapy to pathological response or disease with negative margins

Secondary Outcome Measures

The rate of local failures

Progression-free long-term survival

The rate of distant metastases

Overall long-term survival

The rate of late toxicity according to the RTOG/EORTC scale

The rate of postoperative complications

The rate of early toxicity of neoadjuvant treatment according to the NCI CTCAE (version 4.0)

Full Information

NCT ID

NCT01814969

First Posted

March 18, 2013

Last Updated

May 4, 2015

Sponsor

Maria Sklodowska-Curie National Research Institute of Oncology

1. Study Identification

Unique Protocol Identification Number

NCT01814969

Brief Title

Preoperative Hyperfractionated Radiotherapy or Radiochemotherapy in Locally Advanced Rectal Cancer.

Official Title

Preoperative Hyperfractionated Radiotherapy Versus Combined Radiochemotherapy for Patients With Locally Advanced Rectal Cancer: a Phase III Randomized Trial.

Study Type

Interventional

2. Study Status

Record Verification Date

May 2015

Overall Recruitment Status

Unknown status

Study Start Date

March 2014 (undefined)

Primary Completion Date

December 2016 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Maria Sklodowska-Curie National Research Institute of Oncology

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Clinical objective of the study is to compare the rates of pathologic response, acute toxicity and sphincter preservation with two schedules of preoperative regiment in patients with locally advanced rectal cancer.

Detailed Description

Overview of randomized trials conducted in patients with advanced colorectal cancer with the use of preoperative radiotherapy or radiochemotherapy clearly shows the superiority of combined therapy over surgery alone. In these studies documented a significant reduction in tumor mass as a result of preoperative radiotherapy or radiochemotherapy theoretically increases the chance of performing operations with sphincters preservation, even in cases originally eligible for abdomino - perineal resection. There is the question whether the combination of preoperative hyperfractionated radiotherapy and concurrent chemotherapy may cause the further improvement of treatment outcome in patients with locally advanced rectal cancer. Published in 2012 by Gerard et al. meta-analysis of randomized trials dedicated to the treatment of patients with advanced colorectal cancer, confirms a higher percentage of sphincters preservation in patients operated after more than 5-week interval between neoadjuvant therapy and surgery. Analysis of these issues will be taken in the current study. Comparison of the two treatment regimens as preoperative phase III study with stratification for time interval between the end of radiotherapy or radiochemotherapy and surgery may show differences that have not been seen in previously published data.

6. Conditions and Keywords

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

Rectal Cancer

Keywords

Rectal neoplasm, Preoperative hyperfractionated radiotherapy, Preoperative hyperfractionated radiochemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

260 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hyperfractionated Radiochemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Hyperfractionated Radiotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Hyperfractionated Radiochemotherapy

Other Intervention Name(s)

Hyperfractionated Radiochemotherapy (HRTCT)

Intervention Description

28 x 1.5Gy 2 times a day; gap between the fractions min. 6-8h - duration of treatment 2.5 weeks + simultaneous bolus 5-Fluorouracil (the each cycle consisted of 5-fluorouracil 325 mg/m2 per day) on 1-3 and 16-18 (last 3 days of radiotherapy).

Intervention Type

Radiation

Intervention Name(s)

Hyperfractionated Radiotherapy

Other Intervention Name(s)

Hyperfractionated Radiotherapy (HRT)

Intervention Description

28 x 1.5Gy 2 times a day; gap between the factions min. 6-8h - duration of treatment 2.5 weeks

Primary Outcome Measure Information:

Title

• The rate of patients with downstaging after radiotherapy or radiochemotherapy to pathological response or disease with negative margins

Time Frame

Surrogate endpoint available immediatly after surgery

Secondary Outcome Measure Information:

Title

The rate of local failures

Time Frame

3 years

Title

Progression-free long-term survival

Time Frame

3 years

Title

The rate of distant metastases

Time Frame

3 years

Title

Overall long-term survival

Time Frame

3 years

Title

The rate of late toxicity according to the RTOG/EORTC scale

Time Frame

3 years

Title

The rate of postoperative complications

Time Frame

3 months

Title

The rate of early toxicity of neoadjuvant treatment according to the NCI CTCAE (version 4.0)

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Karnofsky Index 80% or better (Zubrod 0-1) Histological proved diagnosis of rectal cancer (adeno- or mucinous carcinoma) Primary rectal cancer: 3.1. Maximum 12 cm above dentate line (upper limit) 3.2. Staged T2N+ or T3N0 or T3N+ (by endorectal ultrasound or Computed Tomography [CT]/Magnetic Resonance Imaging [MRI] scan) No evidence of metastatic disease as determined by chest X-ray and abdominal ultrasound (or CT-scan of chest and abdomen or other investigations such as Positron Emission Tomography [PET] scan or biopsy if required) Adequate bone marrow function with platelets more than 100 × 10^9/l and neutrophils more than 2.0 × 10^9/l Creatinine clearance more than 50 ml/min Serum bilirubin less than 2.0 × Upper Limit of institutional Normal range (ULN) Written informed consent is obtained prior to commencement of trial treatment (confirmed the signature on the consent form for the proposed project and the standard medical consent form for radiotherapy within the abdominal cavity). Exclusion Criteria: Rectal cancer other than adeno- or mucinous carcinoma Previous or concurrent malignancies, with the exception of adequately treated basal cell carcinoma of the skin Patients with locally advanced inoperable disease, such as T4-tumour Presence of metastatic disease or recurrent rectal tumour Any previous chemotherapy or radiotherapy, and any investigational treatment for rectal cancer Concurrent uncontrolled medical conditions Pregnancy or breast feeding Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease) or myocardial infarction within the last six months Evidence of hereditary colorectal cancer (Hereditary Non-Polyposis Colorectal Cancer [HNPCC] and Familial Adenomatous Polyposis [FAP]) Medical or psychiatric conditions that compromise the patient's ability to give informed consent No agreement for randomisation

Central Contact Person:

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

Adam Idasiak, MD

Phone

+4832278819

aidasiak@op.pl

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

Rafal Suwinski, MD

Phone

+48322788805

rafals@io.gliwice.pl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rafal Suwinski, MD

Organizational Affiliation

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland

Official's Role

Principal Investigator

Facility Information:

Facility Name

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch

City

Gliwice

State/Province

Wybrzeze AK 15

ZIP/Postal Code

44-100

Country

Poland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Adam Idasiak, MD

Phone

+48322788819

aidasiak@op.pl

First Name & Middle Initial & Last Name & Degree

Rafal Suwinski, MD, PhD

12. IPD Sharing Statement

Citations:

PubMed Identifier

17499451

Citation

Suwinski R, Wzietek I, Tarnawski R, Namysl-Kaletka A, Kryj M, Chmielarz A, Wydmanski J. Moderately low alpha/beta ratio for rectal cancer may best explain the outcome of three fractionation schedules of preoperative radiotherapy. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):793-9. doi: 10.1016/j.ijrobp.2007.03.046. Epub 2007 May 17.

Results Reference

background

PubMed Identifier

16730087

Citation

Suwinski R, Wydmanski J, Pawelczyk I, Starzewski J. A pilot study of accelerated preoperative hyperfractionated pelvic irradiation with or without low-dose preoperative prophylactic liver irradiation in patients with locally advanced rectal cancer. Radiother Oncol. 2006 Jul;80(1):27-32. doi: 10.1016/j.radonc.2006.05.001. Epub 2006 May 26.

Results Reference

background

PubMed Identifier

21377377

Citation

Gerard JP, Rostom Y, Gal J, Benchimol D, Ortholan C, Aschele C, Levi JM. Can we increase the chance of sphincter saving surgery in rectal cancer with neoadjuvant treatments: lessons from a systematic review of recent randomized trials. Crit Rev Oncol Hematol. 2012 Jan;81(1):21-8. doi: 10.1016/j.critrevonc.2011.02.001. Epub 2011 Mar 5.

Results Reference

background

PubMed Identifier

33618522

Citation

Idasiak A, Galwas-Kliber K, Rajczykowski M, Debosz-Suwinska I, Zeman M, Stobiecka E, Mrochem-Kwarciak J, Suwinski R. Tumor regression grading after preoperative hyperfractionated radiotherapy/chemoradiotherapy for locally advanced rectal cancers: interim analysis of phase III clinical study. Neoplasma. 2021 May;68(3):631-637. doi: 10.4149/neo_2021_201217N1366. Epub 2021 Feb 24.

Results Reference

derived

PubMed Identifier

28466686

Citation

Idasiak A, Galwas-Kliber K, Behrendt K, Wzietek I, Kryj M, Stobiecka E, Chmielik E, Suwinski R. Pre-operative hyperfractionated concurrent radiochemotherapy for locally advanced rectal cancers: a phase II clinical study. Br J Radiol. 2017 Jun;90(1074):20160731. doi: 10.1259/bjr.20160731. Epub 2017 May 23.

Results Reference

derived

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Preoperative Hyperfractionated Radiotherapy or Radiochemotherapy in Locally Advanced Rectal Cancer.

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