Clinical trial NCT05081687: Brazilian Total Neoadjuvant Therapy Trial
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colorectal Neoplasms
Keywords: Rectal cancer
Neoadjuvant chemo-radiation
Total neoadjuvant therapy
Watch-and-wait
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
First posted: 2021-10-18
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: cCR + PathCR
timeFrame: 12 weeks after the end of chemoradiation
Secondary outcomes:
measure: Rate of R0 resection
timeFrame: 12 weeks
measure: Rate of organ preservation
timeFrame: 6 months after surgery
measure: Overall toxicity
timeFrame: 12 weeks
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital Municipal Vila Santa Catarina
Study officials:
affiliation: Hospital Israelita Albert Einstein
name: Diogo Gomes, MD
role: PRINCIPAL_INVESTIGATOR
References: