Brazilian Total Neoadjuvant Therapy Trial

Colorectal Neoplasms Clinical Trial

— BRAZIL-TNT  

Official title:

A Prospective Randomized Controlled Trial of Total Neo-adjuvant Therapy vs Conventional Chemo-radiation Aiming at Increasing Rates of Clinical Complete Response in Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05081687
• Other study ID #: 4015-20
• Status: Recruiting
• Phase: Phase 3
• Start date: February 20, 2020
• Est. completion date: December 30, 2023

Study information

• Verified date: October 2022
• Source: Hospital Israelita Albert Einstein
• Contact: Diogo Gomes, MD
• Phone: +55-11-2151-8056
• Email: diogo.gomes[@]einstein.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Standard therapy for localized rectal cancer includes chemotherapy and radiation therapy, followed by a "recovery" period of 7-12 weeks, surgery and adjuvant chemotherapy for 3-6 months. Even though this protocol achieves high cure rates, many patients need a rectal amputation with placement of definitive colostomies. About 10-20% of patients have a complete clinical response to chemo-radiation and no tumor can be found in the surgical specimen. These patients can be followed with close surveillance and avid surgery. The aim of this study is to evaluate if a strategy including the use of a highly active chemotherapy called "FOLFIRINOX" during the 12 weeks between the end of radiation therapy and evaluation for surgery increases the rates of complete response and, therefore, allows more patients to undergo non-surgical management.

Description:

Adult patients with locally advanced rectal cancer who have completed conventional long-course chemo-radiation of 54Gy with capecitabine will be randomized 1:1 to a total neo-adjuvant therapy (TNT) protocol or to a control group. Patients in the TNT arm will receive 4 cycles of interval chemotherapy with FOLFIRINOX (5-FU, irinotecan, oxaliplatin) between the end of chemo-radiation and re-staging and those in the control group will undergo standard post-radiation care during this period. All patients will be re-staged with colonoscopy and pelvic MRI 12 weeks after the end of chemo-radiation. Those with a complete clinical response will be placed under a watch-and-wait protocol with digital rectal examinations every 2 months and pelvic MRI and sigmoidoscopy every 6 months. Those wih residual tumors will undergo resection with total mesorectal excision (TME). Patients with a "near complete response", as defined by a multidisciplinary tumor board, will be re-staged at week 16 or 18 after chemo-radiation before undergoing surgery. Adjuvant chemotherapy will be done following the local standard of care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 30, 2023
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 y/o
• Biopsy-confirmed rectal adenocarcinoma
• Tumor Stage T3+ or N+ M0
• Adequate liver function (total bilirubin < = 4.0)
• Adequate kidney function (calculate creatinine-clearance >=30ml/m2/min)
• Adequate bone marrow function (Platelet counts >=90.000, hemoglobin >=8mg/dl, neutrophile count >= 1.500/cm3)
• Completed chemo-radiation with at least 54Gy and capecitabine 1650mg/m2/d

Exclusion Criteria:

• Prior tumor resection
• Prior radiation to the pelvis
• Prior chemotherapy for rectal cancer
• Life expectancy < 6 months
• Unfit for surgery
• Need for urgent/ immediate surgery

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• Folfirinox
5-FU 2400mg/m2; Oxaliplatin 85 mg/m2, Irinotecan 150mg/m2

Locations

Country	Name	City	State
Brazil	Hospital Municipal Vila Santa Catarina	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein	Ministry of Health, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cCR + PathCR	Complete clinical response or pathological response	12 weeks after the end of chemoradiation
Secondary	Rate of R0 resection	Rate of tumor resection with negative margins	12 weeks
Secondary	Rate of organ preservation	Rate of patients who remain colostomy-free	6 months after surgery
Secondary	Overall toxicity	Grade 3-4 toxicities according to CTCAE 4.0	12 weeks

External Links

•   Program of the Brazilian Ministry of Health that us sponsoring the trial