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

NCT05274945 | Completed Phase 2

• 1 other identifier: 122019
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• pathological assessment of response to treatment

  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 Outcomes (1)

• adverse events of chemotherapy

  6 months

Study Arms (2)

total neoadjuvant therapy

EXPERIMENTAL

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; Drug: consolidation chemotherapy; Procedure: TME or APR

standard neoadjuvant therapy

ACTIVE COMPARATOR

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; Procedure: TME or APR

Interventions

Radiotherapy RADIATION

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

Also known as: Radiation therapy

standard neoadjuvant therapy; total neoadjuvant therapy

consolidation chemotherapy DRUG

6 cycles of FOLFOX or CAPOX

Also known as: CTX

total neoadjuvant therapy

TME or APR PROCEDURE

total mesorectal excision or abdominoperineal resection

Also known as: proctectomy

standard neoadjuvant therapy; total neoadjuvant therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Alexandria University: lead

Study Sites (1)

Ahmed Samir Ashoor

Alexandria, Egypt

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy; Consolidation Chemotherapy; Low Density Lipoprotein Receptor-Related Protein-1; Proctectomy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Drug Therapy; LDL-Receptor Related Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, LDL; Receptors, Lipoprotein; Receptors, Cell Surface; Membrane Proteins; Surgical Procedures, Colorectal; Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2022
• First Posted: March 11, 2022
• Study Start: January 1, 2020
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: March 11, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)