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

NCT ID: NCT04643366

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-28
• Study Completion Date: 2033-01-31

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).

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

Neoadjuvant chemotherapy with 2 months of combination oxaliplatin and 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX)

Radiation Therapy

Intervention Type: RADIATION

Pelvic Intensity-modulated radiation therapy (IMRT)

Interventions

Chemotherapy

Neoadjuvant chemotherapy with 2 months of combination oxaliplatin and 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX)

Intervention Type: DRUG

Radiation Therapy

Pelvic Intensity-modulated radiation therapy (IMRT)

Intervention Type: RADIATION

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Khalid Matin, MD

Role: PRINCIPAL_INVESTIGATOR

Massey Cancer Center

Locations

Virginia Cancer Institute

Richmond, Virginia, United States

Site Status: RECRUITING

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status: RECRUITING

VCU Community Memorial Healthcenter

South Hill, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Massey IIT Research Operations, RN

Role: CONTACT

masseyepd@vcu.edu

804-628-6430

Facility Contacts

Sue Moore, MSN, RN

Role: primary

smoore@vacancer.com

804-287-3000 ext. 1261

Massey CTO GI Team, RN

Role: primary

masseygi@vcu.edu

804-628-6430

Massey SIIT Team

Role: primary

masseysiit@vcu.edu

Other Identifiers

HM20020384

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2020-13796

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-18-14260

Identifier Type: -

Identifier Source: org_study_id