Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

March 7, 2022 updated by: Alexandria University

The National Comprehensive Cancer Network (NCCN) guidelines recommend trimodality treatment for patients with middle and low LARC with neoadjuvant chemoradiotherapy (NA-CRT), surgical resection with TME, plus additional chemotherapy (CT), in the adjuvant setting. This has markedly reduced pelvic local recurrence from historically about 25% to about 5-10%. However, the 5-year distant relapse is approximately 30% and continues to be the major cause of rectal cancer death.

One strategy to address this issue is to deliver induction chemotherapy before surgery. Induction chemotherapy may be associated with better treatment compliance and may enable full systemic doses of chemotherapy to be delivered.

The above cited considerations, plus favorable data from preliminary reports exploring this strategy, provides a solid rationale for shifting systemic treatment earlier into the treatment paradigm. The current study will evaluate the efficacy and the safety of total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients as regards effects on tumor downstaging, pathological complete response, surgical difficulty and early functional outcome.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Colorectal cancer is the third most commonly diagnosed cancer and the third leading cause of cancer death in men and women in the USA.

Surgery using the total mesorectal excision (TME) remains the cornerstone of curative therapy for patients with nonmetastatic, locally advanced middle and low rectal cancer (LARC).

The National Comprehensive Cancer Network (NCCN) guidelines recommend trimodality treatment for patients with middle and low LARC with neoadjuvant chemoradiotherapy (NA-CRT), surgical resection with TME, plus additional chemotherapy (CT), in the adjuvant setting.

This has markedly reduced pelvic local recurrence from historically about 25% to about 5-10%. However, the 5-year distant relapse is approximately 30% and continues to be the major cause of rectal cancer death.

Several other trials have attempted to demonstrate the benefits of postoperative chemotherapy as an adjunct to preoperative radiation and surgery. These trials either failed to demonstrate an advantage, or were closed early due to poor accrual. One common theme among these trials is poor compliance with adjuvant chemotherapy. Completion rates for planned chemotherapy ranged from 43 to 74% in these trials.

The current rectal cancer treatment might lead to delay in the initiation of adjuvant chemotherapy especially in patients with postoperative complications, and this delay is theoretically disadvantageous in that it allows a window for growth of distant micrometastases which may already exist.

One strategy to address this issue is to deliver induction chemotherapy before surgery. Induction chemotherapy may be associated with better treatment compliance and may enable full systemic doses of chemotherapy to be delivered.

Other theoretical advantage of induction chemotherapy includes the possibility of shrinking or downstaging a locally advanced tumor, thereby facilitating more effective local treatment.

Initial chemotherapy also permits delivery of chemotherapy agents directly to the primary tumor while it has a fully intact vasculature, undisrupted by radiation or surgery.

It was supposed that increased chemoradiation-to-surgery interval would result in increased fibrosis and surgical difficulty.However, previous studies showed no increase in the technical difficulty of the operation with total neoadjuvant therapy.

The above cited considerations, plus favorable data from preliminary reports exploring this strategy, provides a solid rationale for shifting systemic treatment earlier into the treatment paradigm. The current study will evaluate the efficacy and the safety of total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients as regards effects on tumor downstaging, pathological complete response, surgical difficulty and early functional outcome.

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Alexandria, Egypt
        • Ahmed Samir Ashoor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinical diagnosis of rectal cancer
  • Inferior margin within 12 cm from the anal verge
  • staging must be T3-4,N0 or any T, N +ve

Exclusion Criteria:

  • Recurrent or metastatic disease.
  • Rectal cancer on top of IBD.
  • Hereditary non-polyposis colorectal cancer (HNPCC), or hereditary rectal cancer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: total neoadjuvant therapy
patients will be treated by total neoadjuvant therapy, including concurrent chemoradiotherapy in the form of radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil + Calcium leucoverin for first 4 days and last 3 days of radiotherapy or capecitabine at 825 mg\m2 twice daily. Then, after 2-3 weeks preoperative chemotherapy will be started in the form of 6 cycles of FOLFOX or CAPOX. Then, after 3-4 weeks surgery will be done.
Radiation: Radiotherapy
radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil
Other Names:
  • Radiation therapy
Drug: consolidation chemotherapy
6 cycles of FOLFOX or CAPOX
Other Names:
  • CTX
Procedure: TME or APR
total mesorectal excision or abdominoperineal resection
Other Names:
  • proctectomy
Active Comparator: standard neoadjuvant therapy
patients will be treated by standard neoadjuvant therapy , including concurrent chemoradiotherapy in the form of radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil + Calcium leucoverin for first 4 days and last 3 days of radiotherapy or capecitabine at 825 mg\m2 twice daily . Then, after 6-8 weeks surgery will be performed followed by adjuvant chemotherapy.
Radiation: Radiotherapy
radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil
Other Names:
  • Radiation therapy
Procedure: TME or APR
total mesorectal excision or abdominoperineal resection
Other Names:
  • proctectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pathological assessment of response to treatment
Time Frame: 10 days
The histological sections will be reviewed by the same pathologists and the regression grade will be quantified according to Mandard tumor regression grade with sore 1 representing complete response with no viable tumor cells to score 5 representing no regression.
10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
adverse events of chemotherapy
Time Frame: 6 months
clinical and laboratory follow up to detect hematological and non hematological adverse effects of chemotherapy
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexandria University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Actual)

January 1, 2022

Study Completion (Actual)

January 1, 2022

Study Registration Dates

First Submitted

January 7, 2022

First Submitted That Met QC Criteria

March 7, 2022

First Posted (Actual)

March 11, 2022

Study Record Updates

Last Update Posted (Actual)

March 11, 2022

Last Update Submitted That Met QC Criteria

March 7, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 122019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rectal Cancer

Clinical Trials on Radiotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe