Colorectal Neoplasms
Conditions
Keywords
Rectal cancer, Neoadjuvant chemo-radiation, Total neoadjuvant therapy, Watch-and-wait
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.
Interventions
DRUGFolfirinox
5-FU 2400mg/m2; Oxaliplatin 85 mg/m2, Irinotecan 150mg/m2
Sponsors
Ministry of Health, Brazil
Hospital Israelita Albert Einstein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| cCR + PathCR | 12 weeks after the end of chemoradiation | Complete clinical response or pathological response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Brazil
Contacts
Primary ContactDiogo Gomes, MD
Backup ContactLeticia Brito, MD
Outcome results
None listed