Chemoradiation for Rectal Cancer

Overseen By Sophie Dessureault, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Experimental therapies

Disqualifiers: Prior rectal malignancy, Metastatic disease, Inflammatory bowel disease, Active seizure disorder, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if MRI-guided adaptive chemoradiation therapy can enhance treatment effectiveness for patients with rectal cancer. It combines chemotherapy, including drugs like Capecitabine and the FOLFOX regimen, with radiation, adjusting the treatment based on MRI scans to address tumor changes. The trial suits those diagnosed with rectal adenocarcinoma who can take oral medications and have no history of severe health issues. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the chance to contribute to groundbreaking advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any other experimental therapies while participating in the study. If you are on stable doses of anticoagulant therapy, you may continue with those medications.

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

Research has shown that capecitabine, a drug for colorectal cancer, is usually well-tolerated. In one study, only 12% of patients experienced serious side effects, and most handled the treatment without major issues.

The FOLFOX regimen, a combination of drugs, is generally safe for certain types of colorectal cancer. It is effective, with manageable side effects for most patients, making it a widely accepted treatment worldwide.

Radiation therapy is also a standard part of rectal cancer treatment. Studies indicate it often leads to good results with generally acceptable side effects in both the short and long term.

Overall, these treatments are commonly used and tolerable for many patients. However, individual experiences can differ, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this treatment for rectal cancer because it uses MRI-guided adaptive radiation, a cutting-edge technique that tailors radiation doses based on daily and weekly tumor changes. This approach allows for more precise targeting of the cancer, potentially reducing side effects and improving effectiveness compared to standard radiation treatments. Additionally, the use of MR-linac systems to guide radiation therapy in real-time is a significant advancement, offering the possibility of better outcomes for patients.

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

Research has shown that using capecitabine with oxaliplatin effectively treats colorectal cancer and works as well as 5-FU, a common treatment. In this trial, participants will receive capecitabine-based chemoradiotherapy, which includes radiation therapy. Studies also indicate that the FOLFOX regimen, which includes these drugs, is effective before surgery for rectal cancer, with some patients experiencing a significant reduction in tumor size. Early findings suggest that MRI-guided adaptive radiation therapy, part of this trial, can target tumors more precisely, potentially reducing side effects and improving results. This method uses real-time imaging to adjust treatment based on the tumor's response. Together, these treatments aim to enhance the effectiveness of rectal cancer therapy. ^{1 6 7 8 9}

Who Is on the Research Team?

Jessica Frakes, MD

Principal Investigator

Moffitt Cancer Center

Seth I Felder, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Stage II or III rectal adenocarcinoma, confirmed by MRI. Participants must be able to take oral meds, have good organ function and blood counts, not be pregnant or breastfeeding, and willing to use birth control. Excluded are those with unresectable cancer, prior invasive rectal malignancy, metastatic disease outside the radiation field, HIV/AIDS, inability to undergo MRI due to medical reasons (except controlled anxiety), major surgery within 12 weeks before enrollment, known DPD deficiency.

Inclusion Criteria

My blood clotting tests are normal, or I'm stable on blood thinners like warfarin.

Adequate hematologic function within 28 days before registration as defined in protocol

I can swallow and keep down pills.

Exclusion Criteria

I have been diagnosed with HIV/AIDS.

I have not had cancer treatment in the last 3 years, except for basal cell skin cancer or cervical cancer.

I have not had a heart attack, stroke, or severe chest pain in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Participants receive capecitabine-based chemoradiotherapy with MRI-guided adaptive radiation

6 weeks

Consolidated Chemotherapy

Standard of care consolidated chemotherapy (FOLFOX) is administered following chemoradiotherapy

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• FOLFOX regimen
• Radiation Therapy

Trial Overview The study tests if MRI-guided adaptive chemoradiation therapy can better treat locally advanced rectal cancer. It involves using Capecitabine pills alongside radiation therapy and possibly adding FOLFOX regimen (a combination of chemotherapy drugs) depending on individual responses.

How Is the Trial Designed?

Group I: MRI-guided adaptive radiation Experimental Treatment 3 Interventions

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)

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Viewray Inc.

Industry Sponsor

Trials

13

Recruited

1,100+

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Published Research Related to This Trial

In a study involving 67 patients with stage II and III rectal adenocarcinoma, capecitabine was found to be at least as effective as 5-Fluorouracil in adjuvant chemoradiotherapy, with no significant differences in toxicity or overall survival rates.

There was a notable trend towards improved loco-regional recurrence-free survival in patients treated with capecitabine, suggesting it may work better in combination with radiotherapy compared to 5-Fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer. Kurt, M., Ozkan, L., Kurt, E., et al.[2015]

Capecitabine (Xeloda) is an oral chemotherapy that delivers 5-FU directly to tumors, offering superior response rates and equivalent survival outcomes compared to intravenous 5-FU in first-line metastatic colorectal cancer (MCRC).

Capecitabine has a favorable safety profile, with manageable side effects like hand-foot syndrome and diarrhea, allowing for prompt dose adjustments without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. Sternberg, CN., Reichardt, P., Holland, M.[2015]

In a phase II study involving 54 patients with locally advanced rectal cancer, the combination of capecitabine and radiotherapy resulted in a pathologic complete response rate of 18% and a significant downstaging of tumors in 51% of patients, indicating its efficacy as a neoadjuvant treatment.

The treatment was well tolerated, with manageable side effects, and showed a sphincter preservation rate of 67% for tumors located close to the anal verge, making it a convenient alternative to traditional 5-FU infusion methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Krishnan, S., Janjan, NA., Skibber, JM., et al.[2022]

Neoadjuvant chemoradiation, particularly with fluorouracil (5-FU) plus radiation, is now the preferred treatment for stage II/III rectal cancer, showing lower local relapse rates and better safety compared to postoperative treatments.

Capecitabine (Xeloda) plus radiation has been found to be as effective as 5-FU plus radiation, making it a viable alternative, while combinations with oxaliplatin or irinotecan show promise for improved outcomes and warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation for rectal cancer: is more better? Patel, A., Puthillath, A., Yang, G., et al.[2018]

The Phase I study determined that the maximal tolerated dose of capecitabine combined with standard radiotherapy for rectal cancer is 1600 mg/m²/day, which is important for future treatment protocols.

Dose-limiting toxicities were observed at lower doses, including Grade 3 diarrhea and skin toxicity, indicating that while capecitabine can be effective, careful monitoring for side effects is necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer. Souglakos, J., Androulakis, N., Mavroudis, D., et al.[2019]

Concurrent radiotherapy with chemotherapy (5-fluorouracil and mitomycin-C) is an established treatment for anal canal squamous cell carcinoma, but there is potential for improving tumor control and reducing side effects.

Recent studies are exploring newer chemotherapeutic agents like cisplatin and capecitabine, as well as advanced radiation techniques like intensity-modulated radiation therapy, to enhance treatment efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging treatment strategies for anal cancer. Meyer, J., Willett, C., Czito, B.[2021]

Xeloda (capecitabine) is an oral medication designed to convert into 5-fluorouracil (5-FU) specifically within tumors, potentially increasing anti-tumor activity while reducing systemic toxicity, as shown in various phase I and II trials.

In a phase II trial for colorectal cancer, Xeloda demonstrated a response rate of 21-24% across different regimens, with good tolerability and a longer time to disease progression for the intermittent regimen, which was selected for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Xeloda in colorectal cancer and other solid tumors. Cassidy, J.[2017]

In a phase II study involving 77 previously untreated patients with metastatic colorectal cancer, the combination of capecitabine, irinotecan, and bevacizumab showed a promising progression-free survival rate of 61% at 9 months, with median overall survival of 24.8 months.

While 62% of patients experienced at least one severe adverse event, the regimen was generally well-tolerated, and quality of life remained stable throughout the treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study. Garcia-Alfonso, P., Chaves, M., Muñoz, A., et al.[2018]

In a study of 45 patients with locally advanced rectal cancer, preoperative chemoradiation using capecitabine resulted in significant tumor downstaging, with 63% of primary tumors and 90% of lymph nodes showing downstaging, and a pathologic complete response in 31% of patients.

The treatment was found to be safe and well-tolerated, with no severe hematologic toxicities and manageable Grade 3 side effects, suggesting that capecitabine can effectively enhance surgical options, including sphincter-preserving surgeries for tumors near the anal verge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Kim, JS., Kim, JS., Cho, MJ., et al.[2022]

Citations

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Evaluation of the effectiveness of using capecitabine ... The purpose of this study was to assess and compare the clinical effectiveness of capecitabine monotherapy and that of capecitabine combined with oxaliplatin.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3097797/

Capecitabine in the management of colorectal cancer - PMC Increasing evidence suggests that capecitabine is noninferior as monotherapy and in combination with oxaliplatin when compared to 5-FU in the advanced and ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1773224724012140

Capecitabine in the modern management of colon cancer The 5-year survival rate for stage 4 CRC is less than 10 %, most likely because to the low efficacy of existing therapies. According to the American Cancer ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.54

The efficacy of capecitabine as a salvage treatment in ... The median progression free survival (mPFS) and median overall survival (mOS) was 2.77 (95% CI, 2.495-3.045) and 9.60 months (95% CI, 7.625- ...

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The integration of oral capecitabine into chemoradiation ... A number of phase I/II studies have demonstrated that capecitabine is effective and well tolerated in combination with preoperative radiotherapy in patients ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29661620/

Tolerability, Safety, and Outcomes of Neoadjuvant ... A pathologic complete response was found in 7.5%. The 2- and 5-year DFS and OS rates were 58.5% and 40.7% and 81.0% and 58.2%, respectively. Conclusion: The ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)35639-X/fulltext

Single-agent capecitabine as maintenance therapy after ... This study was to evaluate the efficacy and safety of maintenance therapy with capecitabine versus observation following inductive chemotherapy in patients ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.17_suppl.LBA3513

A phase II study of capecitabine plus concomitant radiation ... After treatment, a clinical response percentage of 81.8% was observed; 3 patients had progression of disease due to local and/or metastases ...

9. tandfonline.com tandfonline.com/doi/full/10.2147/CMR.S11250

Capecitabine in the management of colorectal cancer Increasing evidence suggests that capecitabine is noninferior as monotherapy and in combination with oxaliplatin when compared to 5-FU in the ...