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

NCT ID: NCT05274945

Last Updated: 2022-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2022-01-01

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.

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Radiotherapy

Intervention Type: RADIATION

radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil

consolidation chemotherapy

Intervention Type: DRUG

6 cycles of FOLFOX or CAPOX

TME or APR

Intervention Type: PROCEDURE

total mesorectal excision or abdominoperineal resection

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.

Group Type: ACTIVE_COMPARATOR

Radiotherapy

Intervention Type: RADIATION

radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil

TME or APR

Intervention Type: PROCEDURE

total mesorectal excision or abdominoperineal resection

Interventions

Radiotherapy

radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil

Intervention Type: RADIATION

consolidation chemotherapy

6 cycles of FOLFOX or CAPOX

Intervention Type: DRUG

TME or APR

total mesorectal excision or abdominoperineal resection

Intervention Type: PROCEDURE

Other Intervention Names

Radiation therapy; CTX; proctectomy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexandria University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ahmed Samir Ashoor

Alexandria, , Egypt

Countries

Egypt

Other Identifiers

122019

Identifier Type: -

Identifier Source: org_study_id