MRI-Guided Adaptive Radiation Therapy for Organ Preservation in Rectal Cancer

NCT04808323 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: PRO00040139
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, open-label, phase I design.

Conditions

Rectal Adenocarcinoma

Keywords

MR-guided radiation therapy; Rectal adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• The number of subjects in Cohort A with serious adverse events during radiation.

  This will be measured by NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grades 3, 4 and 5 will be serious.

  Up to 11.5-week period

• The number of subjects in Cohort B with serious adverse events during radiation.

  This will be measured by NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grades 3, 4 and 5 will be serious.

  Up to 11.5-week period

• The number of subjects in Cohort C with serious adverse events during radiation.

  This will be measured by NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grades 3, 4 and 5 will be serious.

  Up to a 12.1-week period.

Secondary Outcomes (13)

• The number of subjects in Cohort A with a complete clinical response (CCR) to treatment.

  31.5 weeks

• The number of subjects in Cohort B with a complete clinical response (CCR) to treatment.

  31.5 weeks

• The number of subjects in Cohort C with a complete clinical response (CCR) to treatment.

  32.1 weeks

• The number of subjects in Cohort A with a noncomplete response (NCR) to treatment.

  31.5 weeks

• The number of subjects in Cohort B with a noncomplete response (NCR) to treatment.

  31.5 weeks

Study Arms (3)

Cohort A

EXPERIMENTAL

Radiation dose: 64 Gy over 32 fractions, prophylactic nodes treated to 50 Gy over 25 fractions, boost to tumor and radiologically positive nodes to total dose of 64 Gy over 32 total fractions.

Drug: Capecitabine; Device: Initial Dose of Radiation before Dose Escalation; Device: Cohort A: Dose Escalation Radiation; Drug: FOLFOX

Cohort B

EXPERIMENTAL

Radiation dose: 68 Gy over approximately 34 fractions, prophylactic nodes treated to 50 Gy over 25 fractions, boost to tumor and radiologically positive nodes to 68 Gy over 34 total fractions.

Drug: Capecitabine; Device: Initial Dose of Radiation before Dose Escalation; Device: Cohort B: Dose Escalation Radiation; Drug: FOLFOX

Cohort C

EXPERIMENTAL

Radiation dose: 72 Gy over 36 total fractions, prophylactic nodes treated to 50 Gy over 25 fractions, boost to tumor and radiologically positive nodes to 72 Gy over 36 total fractions

Drug: Capecitabine; Device: Initial Dose of Radiation before Dose Escalation; Device: Cohort C: Dose Escalation Radiation; Drug: FOLFOX

Interventions

Cohort A: Dose Escalation Radiation DEVICE

Cohort A will receive 14 Gy boost for a total of 64 Gy over 32 total fractions.

Cohort A

Capecitabine DRUG

825 mg/m\^2 twice daily during radiation therapy. (Fluorouracil (5-FU) may be used at the discretion of the treating medical oncologists.) This chemotherapy will be given during the initial radiation dose (50 Gy over 25 frac) and continue for Cohorts A, B, and C.

Also known as: Xeloda

Cohort A; Cohort B; Cohort C

Initial Dose of Radiation before Dose Escalation DEVICE

50 Gy over 25 frac.

Cohort A; Cohort B; Cohort C

Cohort B: Dose Escalation Radiation DEVICE

Cohort B will receive 18 Gy boost for a total of 68 Gy over 34 total fractions.

Cohort B

Cohort C: Dose Escalation Radiation DEVICE

Cohort C will receive 22 Gy boost for a total of 72 Gy over 36 total fractions.

Cohort C

FOLFOX DRUG

After the completion of radiation, subjects will receive up to eight cycles of systemic chemotherapy. (FOLFIRINOX may be used at the discretion of the treating medical oncologists.)

Also known as: Oxaliplatin de Gramont, OxMdG

Cohort A; Cohort B; Cohort C

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18.
• Pathologically confirmed (histologic or cytological), adenocarcinoma of the rectum.
• Determined on staging evaluation to be clinical stage I, II or III.
• No concerning unequivocal or biopsy-proven metastatic disease. Patients are eligible with either no evidence of distant metastatic disease, or "equivocal" evidence of distant metastatic disease, as judged by the multidisciplinary tumor board. This "equivocal" definition can include small lung or liver lesions that are not able to be radiographically characterized otherwise.
• Eastern Cooperative Oncology Group (ECOG) status 0-2 within 45 days of study entry.
• History/physical examination, including collection of weight and vital signs within 45 days prior to start of treatment.
• MR of the rectum is mandatory for staging and follow-up.
• Chest CT scan within 45 days prior to study entry.
• Radiation treatment planning abdominal CT. A mandatory pelvic MR will be done as a simulation (SIM) (ideally with interpretation). The CT SIM will not be done with interpretation. Ability to undergo abdominal MR scans for staging and radiation planning and follow-up is mandatory.
• Laboratory values (CBC, Chem24) 45 days prior to treatment as follows:
• Carcinoembryonic antigen (CEA) (any value).
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3.
• Platelets ≥50,000 cells/mm3.
• Hemoglobin ≥ 8.0 g/dl. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 4 x upper limit of normal.

You may not qualify if:

• Biopsy-proven distant metastatic disease or high clinical concern for metastatic disease and tumor conference consensus of stage IV disease.
• Prior invasive malignancy (except nonmelanomatous skin cancer, noninvasive breast cancer (DCIS), or prostate cancer under active surveillance). Other malignancies are allowed if patient has been disease free for a minimum of three years
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Any major surgery within 28 days prior to study entry, except colonic stent placement, intestinal diversion without resection or vascular access insertion.
• Severe, active comorbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last six months.
• Transmural myocardial infarction within three months prior to study entry.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration.
• Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function.
• Any unresolved intestinal obstruction.
• Acquired immune deficiency syndrome (AIDS), based upon current Centers for Disease Control and Prevention (CDC) definition. Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because patients receiving antiretroviral therapy may experience possible pharmacokinetic interactions with required treatment medications, such as capecitabine.
• Absence of any significant medical comorbidity which would preclude the consideration of major intestinal surgery.
• Participation in another interventional clinical treatment trial while on study (observational trials are permitted).
• Patients taking nonprotocol-specified chemotherapy agents or immune-modulating agents for other medical conditions are not permitted to participate in this trial. Any medication questions should be reviewed by the PI.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; 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

Intervention Hierarchy (Ancestors)

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

Study Officials

• William Hall, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Carrie Peterson, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

414-805-8900; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: March 22, 2021
• Study Start: June 17, 2021
• Primary Completion (Estimated): April 14, 2027
• Study Completion (Estimated): January 20, 2029
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)