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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to determine the feasibility of using magnetic resonance imaging (MRI)-guided adaptive chemoradiation therapy to improve response to treatment.

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.

What data supports the effectiveness of the treatment for rectal cancer?

Research shows that using capecitabine (Xeloda) with radiation therapy is effective in treating locally advanced rectal cancer. This combination helps shrink tumors and is better tolerated than some traditional treatments, making it a good option for patients. ^{1 2 3 4 5}

Is chemoradiation for rectal cancer generally safe for humans?

Capecitabine, a drug used in chemoradiation, is generally well-tolerated and can be taken at home, but it may cause side effects like hand-foot syndrome (redness and swelling of the hands and feet), mouth sores, and diarrhea. When combined with radiotherapy for rectal cancer, studies have been conducted to find the safest dose, and while it is generally safe, some patients may experience treatment-related toxicity, especially with certain drug combinations. ^{6 7 8 9 10}

How is the chemoradiation treatment for rectal cancer unique?

This treatment combines capecitabine, an oral drug that targets cancer cells more selectively, with radiation therapy, offering a convenient alternative to the traditional 5-fluorouracil infusion. It has shown similar effectiveness in reducing tumor size before surgery, making it a promising option for patients with rectal cancer. ^{2 4 10 11 12}

Research Team

Jessica Frakes, MD

Principal Investigator

Moffitt Cancer Center

Seth I Felder, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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.

My rectal cancer cannot be surgically removed due to its spread.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

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

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. [2022]

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

Neoadjuvant chemoradiation for rectal cancer: is more better? [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. [2022]

5. China pubmed.ncbi.nlm.nih.gov

Capecitabine for locally advanced and metastatic colorectal cancer: A review. [2021]

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

Dosing considerations for capecitabine-irinotecan regimens in the treatment of metastatic and/or locally advanced colorectal cancer. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study. [2018]

9. Scotland pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. [2015]

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

Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer. [2019]

11. Greece pubmed.ncbi.nlm.nih.gov

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer. [2015]

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

Current and emerging treatment strategies for anal cancer. [2021]