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

Phase 2 Study of Total Neoadjuvant mFOLFOX and Short-Course Radiotherapy in Resectable Rectal Cancer

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

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Chemotherapy; Radiation: Radiation Therapy

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).

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Massey IIT Research Operations, RN; Phone Number: 804-628-6430; Email: masseyepd@vcu.edu

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23230
      • Recruiting
      • Virginia Cancer Institute
      • Contact: Sue Moore, MSN, RN; Phone Number: 1261 804-287-3000; Email: smoore@vacancer.com
      • Principal Investigator: Purvi Shah, MD
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University Massey Cancer Center
      • Principal Investigator: Khalid Matin, MD
      • Contact: Massey CTO GI Team, RN; Phone Number: 804-628-6430; Email: masseygi@vcu.edu
    • South Hill, Virginia, United States, 23970
      • Recruiting
      • VCU Community Memorial Healthcenter
      • Principal Investigator: Khalid Matin, MD
      • Contact: Massey CTO GI Team; Phone Number: 804-628-6430; Email: masseygi@vcu.edu
    • Tappahannock, Virginia, United States, 22560
      • Not yet recruiting
      • VCU Health Tappahannock Hospital
      • Principal Investigator: Khalid Matin, MD
      • Contact: Massey CTO GI Team; Phone Number: 804-628-6430; Email: masseygi@vcu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concurrent Chemotherapy/ Radiation Therapy; 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.	Drug: Chemotherapy; Neoadjuvant chemotherapy with 2 months of combination oxaliplatin and 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX); Radiation: Radiation Therapy; Pelvic Intensity-modulated radiation therapy (IMRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Three-year disease free survival (DFS)	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).	3 years after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of Adverse events (AEs) per participant	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)	39 Months
Number of patients who do not require an ostomy at time of surgery	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	116 Days
Pathologic complete response (pCR) rate	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).	3 Years after end of treatment
Clinical complete response (cCR) following total neoadjuvant therapy (TNT) based on tumor response	Determine the cCR using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), in patients evaluable for response	3 Years after end of treatment
Progression (PFS) Rate	PFS defined as the time from initiation of chemotherapy until date of progression	3 Years after end of treatment
Overall Survival (OS) Rate	OS defined as the time from initiation of chemotherapy until death by any cause.	3 Years after end of treatment

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Khalid Matin, MD, Massey Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2021
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2033

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Resectable; Rectal
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Therapeutics; Radiotherapy; Drug Therapy
• Other Study ID Numbers: MCC-18-14260; HM20020384 (Other Identifier: Virginia Commonwealth University); NCI-2020-13796 (Other Identifier: NCI CTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No