Clinical trial NCT04643366: Total Neoadjuvant Therapy With mFOLFOX and Short-course Radiation in Resectable Rectal Cancer
Official title: Phase 2 Study of Total Neoadjuvant mFOLFOX and Short-Course Radiotherapy in Resectable Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Resectable
Rectal
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2020-11-25
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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 prior to registration:
* 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
* ECOG Performance Status ≤1
* 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 overlap of RT fields with the planned study treatment
* 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

Primary outcomes:
measure: Three-year disease free survival (DFS)
timeFrame: 3 years after end of treatment
Secondary outcomes:
measure: Pathologic complete response (pCR) rate
timeFrame: 3 Years after end of treatment
measure: Clinical complete response (cCR) following total neoadjuvant therapy (TNT) based on tumor response
timeFrame: 3 Years after end of treatment
measure: The number of Adverse events (AEs) per participant
timeFrame: 39 Months
measure: Progression (PFS) Rate
timeFrame: 3 Years after end of treatment
measure: Overall Survival (OS) Rate
timeFrame: 3 Years after end of treatment
measure: Number of patients who do not require an ostomy at time of surgery
timeFrame: 116 Days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: South Hill
country: United States
facility: VCU Community Memorial Healthcenter
state: Virginia
Study officials:
affiliation: Massey Cancer Center
name: Khalid Matin, MD
role: PRINCIPAL_INVESTIGATOR
References: