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

NCT ID: NCT04808323

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-17
• Study Completion Date: 2029-01-20

Brief Summary

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

Detailed Description

Study Rationale: There are limited studies evaluating real-time adaptive radiation therapy for locally advanced (Stage I-III) rectal adenocarcinoma with the goal of accomplishing organ preservation. We are testing higher doses of radiation therapy, using a novel method of real-time adaptive MRI-based radiation therapy treatment.

Hypothesis: We hypothesize that adaptive magnetic resonance (MR) -guided radiation therapy will result in acceptable toxicity and that a maximum-tolerated dose can be determined in a phase I setting.

Intervention Description: The intervention in this circumstance is higher doses of radiation therapy focused within the tumor given using adaptive MR guidance. Radiation Doses being applied in this study:

Cohort A- 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.

Cohort B- 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.

Cohort C- 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.

Dose-Limiting Toxicity from Radiation Therapy: A dose-limiting toxicity (DLT) as per NCI CTCAE version 5. Specifically, this encompasses the need for additional treatments including the following: transfusion, invasive intervention, or hospitalization indicated. The presence of such a DLT would result in the halting of radiation therapy and impact on the dose levels of radiation therapy applied in the trial.

Conditions

Rectal Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

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.

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: 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.

Initial Dose of Radiation before Dose Escalation

Intervention Type: DEVICE

50 Gy over 25 frac.

Cohort A: Dose Escalation Radiation

Intervention Type: DEVICE

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

FOLFOX

Intervention Type: 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.)

Cohort B

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.

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: 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.

Initial Dose of Radiation before Dose Escalation

Intervention Type: DEVICE

50 Gy over 25 frac.

Cohort B: Dose Escalation Radiation

Intervention Type: DEVICE

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

FOLFOX

Intervention Type: 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.)

Cohort C

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

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: 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.

Initial Dose of Radiation before Dose Escalation

Intervention Type: DEVICE

50 Gy over 25 frac.

Cohort C: Dose Escalation Radiation

Intervention Type: DEVICE

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

FOLFOX

Intervention Type: 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.)

Interventions

Capecitabine

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.

Intervention Type: DRUG

Initial Dose of Radiation before Dose Escalation

50 Gy over 25 frac.

Intervention Type: DEVICE

Cohort A: Dose Escalation Radiation

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

Intervention Type: DEVICE

Cohort B: Dose Escalation Radiation

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

Intervention Type: DEVICE

Cohort C: Dose Escalation Radiation

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

Intervention Type: DEVICE

FOLFOX

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.)

Intervention Type: DRUG

Other Intervention Names

Xeloda; Oxaliplatin de Gramont; OxMdG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18.

2. Pathologically confirmed (histologic or cytological), adenocarcinoma of the rectum.

3. Determined on staging evaluation to be clinical stage I, II or III.

4. 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.

5. Eastern Cooperative Oncology Group (ECOG) status 0-2 within 45 days of study entry.

6. History/physical examination, including collection of weight and vital signs within 45 days prior to start of treatment.

7. MR of the rectum is mandatory for staging and follow-up.

8. Chest CT scan within 45 days prior to study entry.

9. 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.

10. Laboratory values (CBC, Chem24) 45 days prior to treatment as follows:

1. Carcinoembryonic antigen (CEA) (any value).

2. Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3.

3. Platelets ≥50,000 cells/mm3.

4. Hemoglobin ≥ 8.0 g/dl. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)

5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 4 x upper limit of normal.

6. Total bilirubin < 2 x upper normal mg/dL.

7. Alkaline phosphatase < 4 x upper limit of normal.

11. Not on hemodialysis.

12. Ability to swallow oral medications.

13. Patients must be determined by medical oncology to be a candidate for systemic chemotherapy.

14. Patients must provide study-specific informed consent prior to study entry.

15. Negative serum pregnancy test (if applicable).

16. Women of childbearing potential and male participants who are sexually active must practice adequate contraception.

Exclusion Criteria

1. Biopsy-proven distant metastatic disease or high clinical concern for metastatic disease and tumor conference consensus of stage IV disease.

2. 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

3. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.

4. Any major surgery within 28 days prior to study entry, except colonic stent placement, intestinal diversion without resection or vascular access insertion.

5. Severe, active comorbidity, defined as follows:

1. Unstable angina and/or congestive heart failure requiring hospitalization within the last six months.

2. Transmural myocardial infarction within three months prior to study entry.

3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.

4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration.

5. Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function.

6. Any unresolved intestinal obstruction.

7. 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.

8. Absence of any significant medical comorbidity which would preclude the consideration of major intestinal surgery.

6. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during the course of the study and for women three months after study therapy is completed and for men six months after study therapy is completed. This exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

7. Participation in another interventional clinical treatment trial while on study (observational trials are permitted).

8. 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.

9. Poor functional status such that patients are not able to be positioned for radiation treatments.

10. Gadolium allergy.

11. If age over 60, history of hypertension, diabetes or liver transplant, and glomerular filtration rate (GFR) at enrollment is < 30.

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

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

William Hall

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William Hall, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Carrie Peterson, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

Role: CONTACT

cccto@mcw.edu

414-805-8900

Facility Contacts

William Hall, MD

Role: primary

whall@mcw.edu

414-805-4400

Carrie Peterson, MD

Role: backup

cypeterson@mcw.edu

414-955-5783

Other Identifiers

PRO00040139

Identifier Type: -

Identifier Source: org_study_id