Adaptive Radiation for Locally Advanced Rectal Adenocarcinoma

NCT05108428 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: MCC-20911
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the feasibility of using magnetic resonance imaging (MRI)-guided adaptive chemoradiation therapy to improve response to treatment.

Conditions

Rectal Adenocarcinoma

Keywords

colon cancer; rectal cancer

Outcome Measures

Primary Outcomes (1)

• Feasibility of MRI guided dose adaptive chemoradiation therapy

  Investigators will demonstrate if MRI guided dose-adaptation based on MR morphologic objective measurements during primary chemoradiation is feasible. Feasibility will be recorded for each patient as an indicator variable (1=feasible; 0=not feasible)

  Up to 6 weeks

Secondary Outcomes (2)

• Number of Participants with Complete Clinical Response (cCR)

  Up to 6 months

• Number of Participants with Pathological Complete Response (pCR)

  Up to 6 months

Other Outcomes (1)

• Number of Participants with Disease-Free Survival (DFS)

  Up to 5 years

Study Arms (1)

MRI-guided adaptive radiation

EXPERIMENTAL

Patients will receive capecitabine-based chemoradiotherapy (chemotherapy with capecitabine + radiation). Dosing will be modified based on tumor changes measured daily and weekly by MR-guided radiotherapy (MRgRT) utilizing MR-linac (MRL) systems. Chemoradiotherapy will be followed by standard of care consolidated chemotherapy. (FOLFOX)

Drug: Capecitabine; Radiation: Radiation Therapy; Drug: FOLFOX regimen

Interventions

Capecitabine DRUG

Capecitabine 825 mg/m\^2 twice daily orally 5 days per week on days of planned radiation therapy.

Also known as: Xeloda

MRI-guided adaptive radiation

Radiation Therapy RADIATION

Participants will receive varying doses of radiotherapy based on MRI guidance, beginning at 28-33 fractions (1.8 Gray units) .

MRI-guided adaptive radiation

FOLFOX regimen DRUG

Standard of Care FOLFOX regimen consists of 8 cycles (each cycle is 14 days) of 5-fluorouracil, leucovorin, and oxaliplatin. Dosage is as follows: Oxaliplatin 85 mg/m\^2 IV over 2 hours day 1 each cycle. Leucovorin (optional) 400 mg/m\^2 IV over 2 hours day 1 each cycle. 5-fluorouracil bolus\* (optional) 400 mg/m\^2 IV push day 1 of each cycle, and 5-fluorouracil infusion 2400 mg/m\^2 IV continuous infusion over 46 hours day 1 each cycle.

MRI-guided adaptive radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance status of 0, 1
• Histologically confirmed diagnosis of adenocarcinoma of the rectum.
• Clinical Stage II or III as determined on rectal MRI with a distal tumor extent/margin no more than 1 cm proximal to the anterior peritoneal reflection.
• Must have the ability to swallow and retain oral medications
• Adequate hematologic function within 28 days before registration as defined in protocol.
• Adequate hepatic function within 45 days before registration, as defined in protocol.
• Adequate renal function within 28 days before registration, as defined in protocol.
• International normalized ratio of prothrombin time (INR) and prothrombin time (PT) within 28 days before registration must be within normal limits for the lab. Patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history
• Pregnancy test done within 14 days before registration must be negative (for women of childbearing potential only). Pregnancy testing should be performed according to institutional standards.

You may not qualify if:

• Patients with one or more of the following conditions are NOT eligible for this study:
• Rectal cancer histology other than adenocarcinoma (i.e., sarcoma, lymphoma, squamous cell carcinoma, mucosal melanoma, mixed adenoneuroendocrine, anal adenocarcinoma, etc.).
• History of prior invasive rectal malignancy, regardless of disease-free interval or history of familial polyposis syndrome (Lynch, FAP, etc.).
• Patients with a history of antineoplastic treatment for prior malignancy within the past 3 years, except for adequately treated basal cell skin carcinoma or in situ cervical cancer. Note: Hormone therapy for breast cancer is permitted.
• Primary unresectable rectal cancer. Note: A tumor is considered unresectable when invading adjacent organs and an en bloc resection will not achieve negative margins.
• Synchronous colorectal adenocarcinomas.
• Tumor may not be causing symptomatic bowel obstruction
• Definitive clinical or radiologic evidence of metastatic disease or nodal disease outside of the prescribed radiation field. Note: Required imaging studies must have been performed within 28 days prior to enrollment.
• Patients with a history of an arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), myocardial infarction, transient ischemic attack (TIA), Cardiovascular Accident (CVA). Note: Patients with a history of venous thrombotic episodes such as deep venous thrombosis, pulmonary embolus occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Similarly, patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy.
• No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matric metalloprotease inhibitors, thalidomide, anti-VEGF (vascular endothelial growth factor) monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
• Inflammatory bowel disease or have a history of abdominal surgery that may interfere with gastrointestinal motility or absorption.
• Ineligibility to undergo MR imaging or treatment on the MRL due to medical or physical reasons. Anxiety disorders will be permitted if pre-medicated with anxiolytics.
• Active seizure disorder uncontrolled by medication.
• Major surgery within 12 weeks before enrollment.
• Any prior pelvic radiation.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Viewray Inc.: collaborator
• Natera, Inc.: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Rectal Neoplasms; Colonic Neoplasms

Interventions

Capecitabine; Radiotherapy; Folfox protocol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Colonic Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Jessica M Frakes, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

• Seth Felder, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2021
• First Posted: November 5, 2021
• Study Start: December 23, 2021
• Primary Completion: October 9, 2023
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)