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

Sponsor
Alexandria University (Other)
Overall Status
Completed
CT.gov ID
NCT05274945
Collaborator
(none)
58
1
2
24
2.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Radiation: Radiotherapy
  • Drug: consolidation chemotherapy
  • Procedure: TME or APR
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
58 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
Actual Study Start Date :
Jan 1, 2020
Actual Primary Completion Date :
Jan 1, 2022
Actual Study Completion Date :
Jan 1, 2022

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. pathological assessment of response to treatment [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.

    Secondary Outcome Measures

    1. adverse events of chemotherapy [6 months]

      clinical and laboratory follow up to detect hematological and non hematological adverse effects of chemotherapy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ahmed Samir Ashoor Alexandria Egypt

    Sponsors and Collaborators

    • Alexandria University

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alexandria University
    ClinicalTrials.gov Identifier:
    NCT05274945
    Other Study ID Numbers:
    • 122019
    First Posted:
    Mar 11, 2022
    Last Update Posted:
    Mar 11, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 11, 2022