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Neo-adjuvant Short Course Chemo-radiation Therapy in Locally Advanced Rectal Cancer Patients

Primary Purpose

Neo-adjuvant Short Course Chemo-radiotherapy in Locally Advanced Cancer Rectum

Status
Recruiting
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
short course chemo-radiation with 5-fluorouracil
Sponsored by
Assiut University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neo-adjuvant Short Course Chemo-radiotherapy in Locally Advanced Cancer Rectum focused on measuring CCRTH

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pathological confirmed cancer rectum
  • Age between 20-80
  • Clinical T3\4 or node positive disease by MRI

Exclusion Criteria:

  • Early stage cancer rectum
  • M1 disease confirmed by imaging or pathological

Sites / Locations

  • Assiut UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

neoadjuvant chemo-radiation

Arm Description

Short-course RT: 5 fractions of 5 Gy to a total dose of 25 Gy over 5 consecutive days. IMRT plans are generated with 6 MV photons. Dose-escalated concurrent 5-FU: The 3 doses levels of 5-FU are 100, 150, and 200 mg/m2/d. 5-FU will be given by continuous infusion for 20 hours every day starting on the morning of radiation. mFOLFOX: will be given 2 weeks after concurrent chemoradiation for a total of 4 cycles, with each cycle being 14 days. Surgery will be omitted in patients with complete pathological response and proceed to adjuvant chemotherapy. If patient develops progressive or metastatic disease, he/she will be omitted from the investigators study. The surgery will be considered 4-8 weeks after end of therapy. Adjuvant mFOLFOX6: 6 cycles chemotherapy will begin between 4 weeks and 8 weeks after surgery. Toxicities assessment: be using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Outcomes

Primary Outcome Measures

Incidence of treatment adverse events as assessed by National Cancer Institute Common Terminology Criteria for adverse events version 4.0
Dose limiting toxicity is defined as any of the following occurring during chemo radiation or within 21 days from the completion of the treatment like grade 4 non hematological toxicity, grade 4 febrile neutropenia, grade 4 thrombocytopenia or neutropenia toxicity lasting 7 days, grade 3 non hematological toxicity preventing treatment more than 3 days, elevation of ALT or AST more than 10 the upper limit of normal for 7 days

Secondary Outcome Measures

assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery.
assess disease local control measured by disease free survival in months and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery measured by either complete pathological response 0r partial response or no response

Full Information

First Posted
April 25, 2020
Last Updated
February 14, 2022
Sponsor
Assiut University
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1. Study Identification

Unique Protocol Identification Number
NCT04370418
Brief Title
Neo-adjuvant Short Course Chemo-radiation Therapy in Locally Advanced Rectal Cancer Patients
Official Title
Evaluation of the Efficacy and Toxicity of Neo-adjuvant Short Course Radiation Therapy Concurrently With Continuous Infusion 5-fluorouracil in the Management of Locally Advanced Rectal Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2020 (Actual)
Primary Completion Date
June 1, 2021 (Actual)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Assiut University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of this trial is to assess the safety and feasibility of 5-FU when given concurrently with5 Gy x 5 fractions IMRT. The secondary endpoint is to assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery.
Detailed Description
Neo-adjuvant radiotherapy is associated with the improvement of local control for rectal cancer. For locally advanced stage II-III resectable rectal cancer, either preoperative short-course radiotherapy of 25 Gy in 5 consecutive days or long-course chemo-radiotherapy followed by radical Total Meso-rectal Excision is recommended. The Swedish Rectal Cancer Trial has demonstrated the lower rate of early toxicity of short course radiotherapy when compared to chemo-radiation. Short-course irradiation reduced the risk of local recurrence with evidence of overall survival improvement. Short-course regimen is less expensive and more convenient, especially in centers with long waiting lists. Two meta-analyses showed that short course is as effective as long course chemo-radiation in the management of locally advanced rectal cancer in the terms of sphincter preservation rates, down-staging, R0 resection, local control, and grade 3-4 toxicity. Despite reduction in local-regional recurrence risk with neo-adjuvant short course radiotherapy, distant disease recurrence remains a substantial risk for patients with locally advanced disease. In a controlled randomized trial, a short course radiotherapy followed by consolidation chemotherapy prior to surgery yielded superior overall survival outcomes compared to chemo-radiotherapy, without significant differences in disease-free survival, nor local or distant disease control rates. The phase III RAPIDO and STELLAR clinical trials are also evaluating short course radiotherapy and consolidation chemotherapy. The Stockholm III trial was a 3-arm trial that compared short-course RT with the standard 1-week delay to surgery, short-course RT with a 4- to 6-week delay to surgery, and long-course chemoradiation with a 4- to 6-week delay to surgery. The results show similar outcomes between the groups, but delaying the surgery after short-course RT decreased the rates of high-grade toxicity and allowed for an expedited treatment program.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neo-adjuvant Short Course Chemo-radiotherapy in Locally Advanced Cancer Rectum
Keywords
CCRTH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
neoadjuvant chemo-radiation
Arm Type
Other
Arm Description
Short-course RT: 5 fractions of 5 Gy to a total dose of 25 Gy over 5 consecutive days. IMRT plans are generated with 6 MV photons. Dose-escalated concurrent 5-FU: The 3 doses levels of 5-FU are 100, 150, and 200 mg/m2/d. 5-FU will be given by continuous infusion for 20 hours every day starting on the morning of radiation. mFOLFOX: will be given 2 weeks after concurrent chemoradiation for a total of 4 cycles, with each cycle being 14 days. Surgery will be omitted in patients with complete pathological response and proceed to adjuvant chemotherapy. If patient develops progressive or metastatic disease, he/she will be omitted from the investigators study. The surgery will be considered 4-8 weeks after end of therapy. Adjuvant mFOLFOX6: 6 cycles chemotherapy will begin between 4 weeks and 8 weeks after surgery. Toxicities assessment: be using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Intervention Type
Drug
Intervention Name(s)
short course chemo-radiation with 5-fluorouracil
Other Intervention Name(s)
5-fu
Intervention Description
neo-adjuvant short course chemo-radiation in locally advanced rectal cancer patients followed by delayed surgery
Primary Outcome Measure Information:
Title
Incidence of treatment adverse events as assessed by National Cancer Institute Common Terminology Criteria for adverse events version 4.0
Description
Dose limiting toxicity is defined as any of the following occurring during chemo radiation or within 21 days from the completion of the treatment like grade 4 non hematological toxicity, grade 4 febrile neutropenia, grade 4 thrombocytopenia or neutropenia toxicity lasting 7 days, grade 3 non hematological toxicity preventing treatment more than 3 days, elevation of ALT or AST more than 10 the upper limit of normal for 7 days
Time Frame
baseline
Secondary Outcome Measure Information:
Title
assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery.
Description
assess disease local control measured by disease free survival in months and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery measured by either complete pathological response 0r partial response or no response
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathological confirmed cancer rectum Age between 20-80 Clinical T3\4 or node positive disease by MRI Exclusion Criteria: Early stage cancer rectum M1 disease confirmed by imaging or pathological
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
mariam m khalil, MD
Phone
+201223117062
Email
mariammohsenkhalil@aun.edu.eg
First Name & Middle Initial & Last Name or Official Title & Degree
abeer f amin, professor
Email
abeeramin210@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
taha z mohran, professor
Organizational Affiliation
Assiut University
Official's Role
Study Director
Facility Information:
Facility Name
Assiut University
City
Assiut
State/Province
Assuit
ZIP/Postal Code
71515
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariam M Khalil, master
Phone
+201223117062
Email
mariammohsenkhalil@aun.edu.eg

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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Citation
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Neo-adjuvant Short Course Chemo-radiation Therapy in Locally Advanced Rectal Cancer Patients

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