MRI-Guided Radiation + Chemotherapy for Rectal Cancer

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical College of Wisconsin

Must not be taking: Antiretrovirals, Chemotherapy, Immunomodulators

Disqualifiers: Metastatic disease, Prior malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and advanced radiation therapy for rectal cancer. Researchers aim to determine if MRI-guided radiation can more precisely target the cancer while reducing harm to surrounding healthy tissue. Participants will receive specific doses of radiation and chemotherapy drugs such as Capecitabine (Xeloda) and FOLFOX. The trial is open to individuals with rectal cancer that has not spread to distant organs and who can tolerate chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it does mention that patients taking nonprotocol-specified chemotherapy or immune-modulating agents cannot participate. It's best to discuss your current medications with the trial's principal investigator.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MRI-guided adaptive radiation therapy is generally safe, with a low risk of serious side effects. Most patients may experience mild to moderate discomfort, such as some pain, but serious issues like stomach ulcers or tears are rare.

The chemotherapy drugs Capecitabine and FOLFOX are already used to treat other cancers, which provides reassurance about their safety. Capecitabine might cause nausea and diarrhea, while FOLFOX can lead to tiredness and low blood cell counts. These side effects are usually manageable with medical care.

As this trial is in an early stage, it focuses on assessing the safety of these treatments when used together. Participants receive close monitoring to address any side effects promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because MRI-guided adaptive radiation therapy allows for real-time adjustments to radiation delivery, making it more precise than traditional radiation methods. This could minimize damage to healthy tissues and improve outcomes for rectal cancer patients. Additionally, combining this advanced radiation technique with chemotherapy regimens like Capecitabine and FOLFOX might enhance the overall effectiveness of the treatment by targeting cancer cells more aggressively. These innovations offer a promising approach compared to standard treatments, which might not adapt as dynamically to changes in tumor size or location during therapy.

What evidence suggests that this trial's treatments could be effective for rectal cancer?

This trial will evaluate MRI-Guided Adaptive Radiation Therapy (MRIgART) combined with chemotherapy for rectal cancer. Research has shown that MRIgART can effectively treat rectal cancer. Studies have found that MRIgART allows doctors to adjust radiation doses during treatment, targeting the cancer more precisely. This precision helps protect healthy tissue from damage. Additionally, research indicates that MRIgART can safely increase radiation doses to tumors and affected lymph nodes, potentially improving treatment outcomes. Although more studies are needed, early findings suggest this method could enhance the effectiveness of radiation therapy for rectal cancer patients. ^{1 2 3 6 7}

Who Is on the Research Team?

William A. Hall

Principal Investigator

Medical College of Wisconsin

Carrie Peterson, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for adults over 18 with rectal cancer that's not spread far (stage I-III). They must be able to swallow pills, have certain blood counts and organ function, and undergo MRI scans. Pregnant women can't join, nor those with recent major surgery or other serious health issues.

Inclusion Criteria

My condition is confirmed rectal adenocarcinoma.

My cancer has not clearly spread to distant parts of my body.

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, Total bilirubin < 2 x upper normal mg/dL, Alkaline phosphatase < 4 x upper limit of normal, Not on hemodialysis, Ability to swallow oral medications, Patients must be determined by medical oncology to be a candidate for systemic chemotherapy, Patients must provide study-specific informed consent prior to study entry, Negative serum pregnancy test (if applicable), Women of childbearing potential and male participants who are sexually active must practice adequate contraception

Exclusion Criteria

I haven't had major surgery in the last 28 days, except for specific minor procedures.

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, 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, 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, Poor functional status such that patients are not able to be positioned for radiation treatments, Gadolium allergy, If age over 60, history of hypertension, diabetes or liver transplant, and glomerular filtration rate (GFR) at enrollment is < 30.

My cancer has spread to distant parts of my body, confirmed by a biopsy or doctor's consensus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive adaptive MRI-guided radiation therapy with varying doses depending on cohort

11.5-12.1 weeks

Follow-up

Participants are monitored for safety and effectiveness after radiation therapy

4 weeks

Long-term Follow-up

Participants are evaluated for long-term outcomes including ctDNA and quality of life assessments

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• FOLFOX
• MRI-Guided Adaptive Radiation Therapy

Trial Overview The study tests how well patients respond to different doses of radiation therapy guided by MRI scans alongside chemotherapy drugs like Capecitabine and FOLFOX. It's a phase I trial where the safety and best dose of radiation are being figured out.

How Is the Trial Designed?

Group I: Cohort C Experimental Treatment 4 Interventions

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 II: Cohort B Experimental Treatment 4 Interventions

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 III: Cohort A Experimental Treatment 4 Interventions

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.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

The SMART3CM strategy for adaptive radiation therapy in locally advanced pancreatic cancer significantly reduces the number of required optimizations (4 vs 18) compared to the standard FULLOAR method, while maintaining equivalent target coverage (mean V95%=89%).

Using SMART3CM results in lower doses to surrounding organs at risk (OARs) and better adherence to dose constraints, demonstrating its efficacy in sparing healthy tissue during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast and robust online adaptive planning in stereotactic MR-guided adaptive radiation therapy (SMART) for pancreatic cancer. Bohoudi, O., Bruynzeel, AME., Senan, S., et al.[2022]

MRI-guided radiation therapy (MRIgRT) offers significant advantages over traditional CT-based methods, particularly for pelvic tumors, by providing better soft-tissue contrast and the ability to visualize organ motion, which can lead to more precise targeting of aggressive tumor areas.

MRIgRT allows for real-time adaptation of treatment, reducing toxic effects on surrounding healthy tissues and improving overall oncologic outcomes, especially in mobile pelvic structures like those found in prostate, cervical, and bladder cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-guided Pelvic Radiation Therapy: A Primer for Radiologists. Zhong, J., Kobus, M., Maitre, P., et al.[2023]

In a study of 100 prostate cancer patients treated with 1.5T MR-guided stereotactic body radiotherapy (SBRT), the treatment showed promising safety outcomes with manageable acute and late toxicity, including only a few cases of significant urinary and gastrointestinal side effects.

Quality of life assessments indicated substantial improvement in overall health and comfort after treatment, although sexual function remained a concern, highlighting the need for further long-term studies to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1.5T MR-Guided Daily-Adaptive SBRT for Prostate Cancer: Preliminary Report of Toxicity and Quality of Life of the First 100 Patients. Alongi, F., Rigo, M., Figlia, V., et al.[2022]

In a phase 1 trial involving 22 prostate cancer patients, stereotactic MR-guided adaptive radiation therapy (SMART) demonstrated a low risk of acute urinary (22.7%) and gastrointestinal (4.5%) toxic effects, with no severe grade 3+ events reported.

Daily plan adaptation during SMART significantly improved dosimetry, ensuring that 100% of treatment plans were optimized to protect critical organs, highlighting the importance of real-time adjustments in radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Prostate Stereotactic Body Radiation Therapy With Daily Online Plan Adaptation: Results of a Prospective Phase 1 Trial and Supplemental Cohort. Leeman, JE., Cagney, DN., Mak, RH., et al.[2022]

MRI-guided radiotherapy (MRIgRT) has been effectively used in treating 642 patients over 4.5 years, with breast and gastrointestinal cancers being the most common indications, showcasing its broad applicability in radiation oncology.

Adaptive radiotherapy (ART) was utilized in 190 patients, with a significant 67.6% of treatment fractions being adapted, particularly for abdominal cancers, indicating the technology's ability to adjust treatment based on real-time anatomical changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience. Henke, LE., Contreras, JA., Green, OL., et al.[2023]

This study analyzed 171 MRI scans from 8 patients with locally advanced rectal cancer during neoadjuvant radiochemotherapy, finding that MRI can help predict treatment response, specifically identifying volumetric changes that correlate with pathological complete response (pCR).

The research established that T2- and diffusion-weighted imaging (DWI) volumetric measurements at two and four weeks into treatment were significant predictors of pCR, while average tumor ADC values were not effective in distinguishing between treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring MR regression patterns in rectal cancer during neoadjuvant radiochemotherapy with daily T2- and diffusion-weighted MRI. Bostel, T., Dreher, C., Wollschläger, D., et al.[2021]

In a study of 44 patients with inoperable pancreatic cancer, those receiving high-dose MRgRT (biologically effective dose >70) showed a significant improvement in 2-year overall survival (49% vs 30%) compared to those receiving standard-dose treatment.

High-dose MRgRT was associated with lower rates of severe gastrointestinal toxicity, as no grade 3 or higher GI toxicity was reported in the high-dose group, while three patients in the standard-dose group experienced such toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Rudra, S., Jiang, N., Rosenberg, SA., et al.[2021]

In a study of 36 patients with locally advanced pancreatic cancer, daily plan adaptation during MR-guided radiation therapy significantly improved target coverage and reduced high doses to nearby organs at risk, with compliance to institutional constraints increasing from 43.9% to 83.3%.

Adaptive planning was beneficial in about 52.8% of treatment fractions, particularly when the distance from the tumor to adjacent organs at risk was 3 mm or less, highlighting the importance of personalized treatment approaches in radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of patients with locally advanced pancreatic cancer benefitting from plan adaptation in MR-guided radiation therapy. Bohoudi, O., Bruynzeel, AME., Meijerink, MR., et al.[2020]

The newly developed end-to-end quality assurance (QA) workflow for MR-guided online adaptive radiation therapy (MRgOART) takes only 10 minutes to complete and effectively checks the performance and connectivity of all components involved, ensuring safe and accurate treatment delivery.

This QA process has successfully identified communication issues and discrepancies in isocenter shifts, allowing for timely resolutions before patient treatment, thus enhancing the reliability of MRgOART in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A daily end-to-end quality assurance workflow for MR-guided online adaptive radiation therapy on MR-Linac. Chen, X., Ahunbay, E., Paulson, ES., et al.[2020]

Stereotactic MRI-guided adaptive radiotherapy (SMART) demonstrated a 2-year local control rate of 74% for abdominal and pelvic tumors, with significantly better outcomes for lesions treated with higher doses (BED10 ≥100).

The treatment was associated with minimal morbidity, with only 0.9% of patients experiencing acute grade three toxicities and no grade four toxicities, indicating that SMART may reduce the risk of gastrointestinal side effects compared to traditional SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of stereotactic magnetic resonance image-guided adaptive radiotherapy for primary and metastatic tumors in the abdomen and pelvis. Yoon, SM., Luterstein, E., Chu, FI., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053429623000681

MRI-Guided Adaptive Radiation Therapy Approximately 94% of their patients developed at least grade 2 pain and many patients developed severe GI ulceration or perforation.33 MRIgRT improves ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11395642/

Efficacy and safety of MR-guided adaptive simultaneous ... The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04808323

MRI-Guided Adaptive Radiation Therapy for Organ ... Study Rationale: There are limited studies evaluating real-time adaptive radiation therapy for locally advanced (Stage I-III) rectal adenocarcinoma with the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11367860/

Dose tracking assessment for magnetic resonance guided ... This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the ...

5. phiro.science phiro.science/article/S2405-6316(25)00052-1/fulltext

Efficient strategy for magnetic resonance image-guided ... This retrospective study included 50 fractions from 10 patients with rectal cancer undergoing preoperative radiotherapy.

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2818117

Safety and Tolerability of Online Adaptive High-Field ... The findings of this study suggest that online adaptive MR-guided radiotherapy is associated with a low risk of high-grade acute toxic effects.

7. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/radiol.2020202747

MRI-guided Radiation Therapy: An Emerging Paradigm in ... This review describes emerging innovations in offline and online MRI-guided RT, exciting opportunities they offer for advancing research and clinical care.