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

Trial Summary

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.

What data supports the effectiveness of the treatment MRI-Guided Radiation + Chemotherapy for Rectal Cancer?

Research on MRI-guided radiation therapy (MRgRT) shows promise in improving treatment outcomes by better targeting tumors and sparing healthy organs, as seen in studies on pancreatic and prostate cancers. This suggests that similar benefits might be expected for rectal cancer, potentially enhancing the effectiveness of the treatment. ^{1 2 3 4 5}

Is MRI-guided radiation therapy safe for treating cancer?

MRI-guided radiation therapy has been used safely in treating various cancers, including prostate and abdominal tumors. Studies have shown that it can reduce side effects compared to traditional methods, with some patients experiencing mild to moderate side effects like urinary or gastrointestinal issues, which generally improve over time. ^{5 6 7 8 9}

What makes MRI-Guided Radiation + Chemotherapy for Rectal Cancer unique compared to other treatments?

This treatment is unique because it uses MRI-guided radiation therapy, which provides better imaging of soft tissues and allows for real-time adjustments during treatment to target tumors more precisely while sparing healthy organs. This approach can potentially reduce side effects and improve outcomes compared to traditional radiation therapy. ^{4 5 6 9 10}

What is the purpose of this trial?

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

Research Team

William A. Hall

Principal Investigator

Medical College of Wisconsin

Carrie Peterson, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Exploring MR regression patterns in rectal cancer during neoadjuvant radiochemotherapy with daily T2- and diffusion-weighted MRI. [2021]

3. Ireland pubmed.ncbi.nlm.nih.gov

Fast and robust online adaptive planning in stereotactic MR-guided adaptive radiation therapy (SMART) for pancreatic cancer. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Identification of patients with locally advanced pancreatic cancer benefitting from plan adaptation in MR-guided radiation therapy. [2020]

5. United States 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

MRI-guided Pelvic Radiation Therapy: A Primer for Radiologists. [2023]

7. Switzerland 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A daily end-to-end quality assurance workflow for MR-guided online adaptive radiation therapy on MR-Linac. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience. [2023]