Total Neoadjuvant Therapy With mFOLFOX and Short-course Radiation in Resectable Rectal Cancer

Virginia Commonwealth University (VCU)

Status and phase: Enrolling; Phase 2

Conditions: Rectal Cancer

Treatments: Radiation: Radiation Therapy; Drug: Chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT04643366

NCI-2020-13796 (Other Identifier)

MCC-18-14260

HM20020384 (Other Identifier)

Details and patient eligibility

About

This is phase 2 trial of neoadjuvant therapy and short-course radiotherapy in resectable rectal cancer.

Full 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).

Enrollment: 54 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 1 patient group

Concurrent Chemotherapy/ Radiation Therapy

Experimental group

Description:

5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) four 14-day cycles will be given before CRT starts. Pelvic Intensity-modulated radiation therapy (IMRT): 25 Gy in 5 fractions over 5 days + Continuous infusion 5-fluorouracil (5-FU) for 4 days (96 hours) followed by four 14-day cycles of (mFOLFOX6) to be given after CRT ends.

Treatment:

Drug: Chemotherapy

Radiation: Radiation Therapy