BRAZIL-TNT: Brazilian Total Neoadjuvant Therapy Trial

Sponsor

Hospital Israelita Albert Einstein (Other)

Overall Status

Recruiting

CT.gov ID

NCT05081687

Collaborator

Ministry of Health, Brazil (Other)

150

Enrollment

Location

Arms

46.3

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms	Drug: Folfirinox	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be randomized 1:1 to one of two arms: TNT and conventional therapy (control). Randomization will be stratified by study site and tumor stage (II vs III)Patients will be randomized 1:1 to one of two arms: TNT and conventional therapy (control). Randomization will be stratified by study site and tumor stage (II vs III)

Masking:

None (Open Label)

Masking Description:

This is an open-label study

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 20, 2020

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Total neoadjuvant therapy (TNT) 4 cycles of mFOLFIRINOX every 14 days: Oxaliplatin 85 mg/m2 Irinotecan 150mg/m2 5-FU 2.400mg/m2 Dexamethasone 12mg Atropine 0.5mg Netupitant/palonosetron	Drug: Folfirinox 5-FU 2400mg/m2; Oxaliplatin 85 mg/m2, Irinotecan 150mg/m2 Other Names: mFOLFIRINOX FOLFOXIRI 5-FU, oxaliplatin, irinotecan
No Intervention: Standard of care Standard post-radiation care

Arm

Intervention/Treatment

Experimental: Total neoadjuvant therapy (TNT)

4 cycles of mFOLFIRINOX every 14 days: Oxaliplatin 85 mg/m2 Irinotecan 150mg/m2 5-FU 2.400mg/m2 Dexamethasone 12mg Atropine 0.5mg Netupitant/palonosetron

Drug: Folfirinox

5-FU 2400mg/m2; Oxaliplatin 85 mg/m2, Irinotecan 150mg/m2

Other Names:

mFOLFIRINOX

FOLFOXIRI

5-FU, oxaliplatin, irinotecan

No Intervention: Standard of care

Standard post-radiation care

Outcome Measures

Primary Outcome Measures

cCR + PathCR [12 weeks after the end of chemoradiation]
Complete clinical response or pathological response

Secondary Outcome Measures

Rate of R0 resection [12 weeks]
Rate of tumor resection with negative margins
Rate of organ preservation [6 months after surgery]
Rate of patients who remain colostomy-free
Overall toxicity [12 weeks]
Grade 3-4 toxicities according to CTCAE 4.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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