Reduced-Dose Radiation + Chemotherapy for Anal Cancer

(REDEL Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: University of Cincinnati

Must be taking: Capecitabine, Mitomycin C

Disqualifiers: Prior pelvic radiation, Autoimmune, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

To determine the efficacy of reduced elective nodal radiation in anal cancer patients undergoing chemoradiation in reducing toxicity compared to standard nodal irradiation.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be able to receive treatment with capecitabine and Mitomycin C, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Reduced-Dose Radiation + Chemotherapy for Anal Cancer?

Research shows that using capecitabine (an oral chemotherapy drug) and mitomycin C with radiation therapy is effective for treating anal cancer, similar to the standard treatment with 5-fluorouracil and mitomycin C. Studies have confirmed that capecitabine can replace 5-fluorouracil successfully, maintaining treatment effectiveness. ^{1 2 3 4 5}

Is the combination of reduced-dose radiation and chemotherapy, including drugs like Mitomycin C and Capecitabine, generally safe for humans?

Mitomycin C, used in various cancer treatments, has shown tolerable acute side effects like mild nausea and vomiting, but can cause serious long-term effects such as blood cell suppression, lung, kidney, and heart issues. Capecitabine combined with Mitomycin C has been used in colorectal cancer with manageable side effects, including hand-foot syndrome and diarrhea, suggesting a favorable safety profile. ^{6 7 8 9 10}

How does the reduced-dose radiation and chemotherapy treatment for anal cancer differ from other treatments?

This treatment is unique because it combines reduced-dose radiation with chemotherapy drugs capecitabine and mitomycin C, aiming to maintain effectiveness while potentially reducing side effects. The use of capecitabine, an oral drug, offers a more convenient administration compared to traditional intravenous chemotherapy. ^{3 11 12 13 14}

Research Team

Eligibility Criteria

This trial is for adults over 18 with locally advanced anal cancer, confirmed by PET scan and CT/MRI within the last 60 days. Eligible patients have specific stages of cancer (T1-4N+M0 or T3/T4N0M0) and may include those with large tumors (>4 cm) or HPV-related perianal cancer extending to the anal verge. Participants must be physically able to undergo treatment, have a creatinine clearance >30 ml/min, and understand consent.

Inclusion Criteria

I am fully active or able to carry out light work.

I am 18 years old or older.

My cancer was removed but it had spread to my lymph nodes or was large at the primary site.

Exclusion Criteria

I have had radiation therapy in the pelvic area before.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine

I do not have any severe illnesses that would stop me from receiving radiation or capecitabine.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive reduced elective nodal radiation (30.6 Gy) with concurrent Capecitabine and Mitomycin C over 5.5 to 6 weeks

5.5 to 6 weeks

28-30 visits (in-person, Monday to Friday)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of toxicity and disease-free survival

3 to 6 months

Visits at 3 and 6 months post-treatment

Long-term Follow-up

Participants are followed for overall survival and colostomy-free survival

3 years

Treatment Details

Interventions

• Capecitabine (Anti-metabolites)
• Mitomycin c (Alkylating agents)
• Radiation (reduced elective nodal dose (30.6 Gy)) (Radiation)

Trial Overview The REDEL Trial is testing whether reducing the radiation dose to elective nodal areas (to 30.6 Gy), while undergoing chemotherapy with Capecitabine and Mitomycin C, can lessen toxicity without compromising effectiveness in treating anal cancer compared to standard radiation doses.

Participant Groups

Group I: Reduced Elective Dose + Concurrent Capecitabine/Mitomycin C Experimental Treatment 3 Interventions

Reduced elective nodal dose (30.6 Gy); (28- 30 fractions given M-F for approximately 5.5 to 6 weeks) Capecitabine 825 mg/m2 BID on days with RT Mitomycin C 10 mg/m2 slow IV push Days 1 and 29

Capecitabine is already approved in Canada, Japan for the following indications:

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Vermont Burlington, VT

University of Cincinnati Medical Center Cincinnati, OH

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Patients Recruited

639,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EXTRA--a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. Glynne-Jones, R., Meadows, H., Wan, S., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. Thind, G., Johal, B., Follwell, M., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled Analysis of external-beam RADiotherapy parameters in phase II and phase III trials in radiochemotherapy in Anal Cancer (PARADAC). Rivin Del Campo, E., Matzinger, O., Haustermans, K., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. Flam, M., John, M., Pajak, TF., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of a phase II study of high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients with anal canal cancer: a French cooperative study. Peiffert, D., Seitz, JF., Rougier, P., et al.[2020]

A short-term intensive schedule of intravesical Mitomycin C (MMC) showed good ablative power in treating recurrent non-muscle-invasive bladder cancer (NMIBC), with a complete response rate of 61.7% in the intensive treatment group after 39 months.

No systemic toxicity was observed in patients, and local toxicities were similar between treatment groups, indicating that this MMC schedule is safe and could potentially replace traditional surgical methods in selected NMIBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoablation with Intensive Intravesical Mitomycin C Treatment: A New Approach for Non-muscle-invasive Bladder Cancer. Racioppi, M., Di Gianfrancesco, L., Ragonese, M., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer. Rao, S., Cunningham, D., Price, T., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitomycin-C in breast cancer. Hortobagyi, GN.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitomycin C in the chemotherapy of advanced breast cancer. Garewal, HS.[2018]

In a study involving 35 patients, MitoExtra (ME) was found to be bioequivalent to mitomycin C (MMC) in terms of pharmacokinetics, indicating that ME effectively releases MMC in the body.

Both treatments showed similar levels of hematologic and nonhematologic toxicities, but ME had no infusion-related complications, suggesting it may be a safer alternative to MMC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I bioequivalency study of MitoExtra and mitomycin C in patients with solid tumors. Kozuch, P., Hoff, PM., Hess, K., et al.[2017]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitomycin in anal canal carcinoma. Cummings, BJ., Keane, TJ., O'Sullivan, B., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous integrated boost-intensity modulated radiation therapy with concomitant capecitabine and mitomycin C for locally advanced anal carcinoma: a phase 1 study. Deenen, MJ., Dewit, L., Boot, H., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Outcome of simultaneous radiochemotherapy of anal carcinoma]. Fraunholz, IB., Adamietz, IA., Lorenz, M., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Three cases of radiotherapy combined with S-1 and mitomycin C for anal canal squamous cell carcinomas]. Shiozawa, M., Nishimura, K., Nonaka, T., et al.[2013]

References

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

EXTRA--a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. [2022]

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

Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pooled Analysis of external-beam RADiotherapy parameters in phase II and phase III trials in radiochemotherapy in Anal Cancer (PARADAC). [2020]

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

Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Preliminary results of a phase II study of high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients with anal canal cancer: a French cooperative study. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Chemoablation with Intensive Intravesical Mitomycin C Treatment: A New Approach for Non-muscle-invasive Bladder Cancer. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer. [2018]

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

Mitomycin-C in breast cancer. [2018]

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

Mitomycin C in the chemotherapy of advanced breast cancer. [2018]

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

Phase I bioequivalency study of MitoExtra and mitomycin C in patients with solid tumors. [2017]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Mitomycin in anal canal carcinoma. [2018]

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

Simultaneous integrated boost-intensity modulated radiation therapy with concomitant capecitabine and mitomycin C for locally advanced anal carcinoma: a phase 1 study. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

[Outcome of simultaneous radiochemotherapy of anal carcinoma]. [2013]

14. Japan pubmed.ncbi.nlm.nih.gov

[Three cases of radiotherapy combined with S-1 and mitomycin C for anal canal squamous cell carcinomas]. [2013]