Rectal Cancer
Conditions
Keywords
Resectable, Rectal
Brief summary
This is phase 2 trial of neoadjuvant therapy and short-course radiotherapy in resectable rectal cancer.
Detailed description
This trial involves 4 cycles of systemic chemotherapy followed by short-course RT with concurrent 5-FU neoadjuvant chemoradiotherapy (CRT) and subsequent consolidation with 4 cycles of systemic chemotherapy prior to surgery or, for those who achieve cCR, the option of non-operative active surveillance.Three-year disease free survival (DFS) defined as the percentage of patients alive without recurrence of disease at 3 years measured from the date of clinical complete response (cCR) or date of total mesorectal excision (TME) at surgery (whichever is earlier).
Interventions
DRUGChemotherapy
Neoadjuvant chemotherapy with 2 months of combination oxaliplatin and 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX)
RADIATIONRadiation Therapy
Pelvic Intensity-modulated radiation therapy (IMRT)
Sponsors
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologic diagnosis of adenocarcinoma of the rectum (diagnosis by tissue biopsy) within 90 days prior to registration. At least a portion of the tumor must be located below the peritoneal reflection or begin within 12 cm of the anal verge on flexible endoscopy * Clinically staged (AJCC 8th ed.) T3-4 N0 M0 or T any N1-2 M0 based upon the following minimum diagnostic workup: * Colonoscopy, unless patient presents with an obstructing lesion * Within 30 days before initiating MFOLFOX6 treatment: * History/physical examination * Imaging to exclude distant metastases: either contrast-enhanced CT of the chest, abdomen, and pelvis; or whole-body PET-CT; or MRI * Pelvic MRI (preferred) or transrectal ultrasound (TRUS) for T staging Note: Patients may have initiated standard mFOLFOX6 treatment before study registration provided that they met the above criteria before initiating treatment and can feasibly continue to CRT according to the timeline described in Section * ECOG Performance Status ≤2 * Age ≥ 18 years * Adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,200 cells/mm3 * Platelets ≥ 100,000 cells/mm3 * Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥8.0 g/dL is acceptable.) * Adequate liver and renal function defined as follows: * AST and alkaline phosphatase \< 2.5 x upper limit of normal (ULN) * Bilirubin ≤ 2.5 ULN * Calculated creatinine clearance (CrCl) \> 30 mL/min using Cockcroft-Gault formula as calculated by the standard Cockcroft-Gault equation using age, actual weight, creatinine, and gender * Must be deemed a candidate for curative resection by the surgical oncologist who will be performing the operation * Women of childbearing potential (WCBP) must have a negative serum pregnancy test performed within 7 days prior to the start of chemotherapy. * WCBP and men must agree to use a medically accepted form of birth control during the treatment and for 3 months following completion of chemotherapy. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Prior RT that would result in unsafe overlap of RT fields with the planned study treatment, per the treating radiation oncologist * Clinically significant cardiac disease, including major cardiac dysfunction, that in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin. * Serious (ie, ≥ grade 3) uncontrolled infection * Pulmonary or respiratory condition that, in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin. * Major surgery within 28 days of study enrollment (other than diverting colostomy) * History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) requiring significant intervention (eg, hospitalization, surgery, immunosuppressive medications) that would, in the opinion of the investigator, preclude study therapy * Prior known allergic reaction to 5-fluorouracil, leucovorin, or oxaliplatin * Known dipyrimidine dehydrogenase deficiency (DPD) * Any evidence of distant metastases (M1) * Pregnant or breast feeding * Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Three-year disease free survival (DFS) | 3 years after end of treatment | The three-year disease free survival (DFS) defined as the number of patients alive without recurrence of disease at 3 years measured from the date of clinical complete response (cCR) or date of total mesorectal excision (TME) at surgery (whichever is earlier). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response (pCR) rate | 3 Years after end of treatment | The number of patients that achieve pathologic complete response(pCR)(defined as negative surgical margins and no evidence of residual viable tumor) at time of total mesorectal excision (TME). |
| Clinical complete response (cCR) following total neoadjuvant therapy (TNT) based on tumor response | 3 Years after end of treatment | Determine the cCR using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), in patients evaluable for response |
| The number of Adverse events (AEs) per participant | 39 Months | The number of Adverse events (AEs) per participant characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v. 5.0) |
| Progression (PFS) Rate | 3 Years and 5 years after end of treatment | PFS defined as the time from initiation of chemotherapy until date of progression |
| Overall Survival (OS) Rate | 5 Years after end of treatment | OS defined as the time from initiation of chemotherapy until death by any cause. |
| Number of patients who do not require an ostomy at time of surgery | 116 Days | After neoadjuvant therapy is complete patients will undergo assessment of disease status prior to determination of whether they will proceed to surgical resection or active surveillance |
Countries
United States
Contacts
CONTACTMassey IIT Research Operations, RN
PRINCIPAL_INVESTIGATORKhalid Matin, MD
Massey Cancer Center
Outcome results
None listed