Reduced-Dose Radiation + Chemotherapy for Anal Cancer

(REDEL Trial)

Recruiting at 2 trial locations

Overseen By Jordan Kharofa, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Cincinnati

Must be taking: Capecitabine, Mitomycin C

Disqualifiers: Prior pelvic radiation, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 31

Duration: 5.5 to 6 weeks

33 Participants Needed

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}

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.

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
• Mitomycin c
• Radiation (reduced elective nodal dose (30.6 Gy))

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 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?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Findings from Research

In a phase II trial involving 31 patients with epidermoid anal carcinoma, the combination of capecitabine, mitomycin C, and radiotherapy showed a high complete clinical response rate of 77% after 4 weeks, indicating strong efficacy.

The treatment was well tolerated with minimal toxicity; only one patient experienced severe diarrhea, and there were no treatment-related deaths, suggesting a favorable safety profile for future studies.

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]

In a study of 66 patients with stage I-III anal canal squamous cell carcinoma, the combination of capecitabine (CAP) and mitomycin C (MMC) during chemo-radiotherapy was well tolerated, with a high dose intensity of 98% and a low rate of severe toxicity (20% experienced dose reductions).

After a median follow-up of 20 months, 94% of patients showed no evidence of cancer relapse, suggesting that CAP may be an effective alternative to 5-fluorouracil in this treatment setting, although further research is needed to confirm outcomes with varying radiation doses.

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]

In a pooled analysis of 1343 patients with anal cancer, longer overall treatment time (OTT) was associated with a higher rate of locoregional failure (22.8%), indicating that prolonged treatment duration may negatively impact patient outcomes.

Five-year progression-free survival (PFS) was significantly higher in women and patients with smaller tumors, highlighting the importance of gender and tumor size in treatment outcomes, with an overall PFS rate of 65.7%.

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]

In a phase III trial involving 310 patients, the addition of mitomycin (MMC) to the chemoradiation regimen significantly improved colostomy-free survival (71% vs. 59%) and disease-free survival (73% vs. 51%) compared to treatment with only radiotherapy and fluorouracil, despite higher toxicity rates in the MMC group.

Salvage chemoradiation was effective in 50% of patients with residual tumors after initial treatment, suggesting it is a viable option before considering radical surgery.

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]

In a prospective trial involving 30 patients with advanced anal canal carcinomas, the combination of 5-fluorouracil and cisplatin with radiotherapy showed a high tumor response rate, with 96% of patients achieving a complete response after treatment.

The treatment was generally well tolerated, with manageable toxicity levels; only one patient experienced a serious adverse event (pulmonary embolism), and no toxic deaths occurred, indicating a favorable safety profile.

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]

In a study of 84 previously untreated patients with advanced colorectal cancer, the combination of capecitabine and mitomycin C showed an overall response rate of 38%, with an additional 33.3% of patients achieving stable disease over 12 weeks.

The treatment demonstrated a favorable safety profile, with manageable side effects such as hand-foot syndrome (19.7%) and diarrhea (10%), making it a potential option for patients who cannot tolerate other chemotherapy regimens.

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]

Mitomycin-C, an antitumor antibiotic, has shown an overall response rate of 35% when administered intermittently at high doses (20 mg/m2 every 6 to 8 weeks), making it an effective treatment option for certain cancers.

While acute toxicities like mild nausea and vomiting are manageable, chronic toxicities such as myelosuppression and pulmonary toxicity require careful monitoring, especially when incorporating mitomycin-C into breast cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Mitomycin C is effective in salvage therapy for breast cancer patients who have not responded to first-line treatments, despite its potential side effect of prolonged myelosuppression.

The choice of salvage chemotherapy should consider previous treatments, with combinations including mitomycin C, doxorubicin, and vinca alkaloids being preferred to minimize disruption to the patient's lifestyle.

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]

In a study of 110 patients with primary epidermoid anal cancers, the addition of mitomycin to radiation therapy significantly improved tumor control rates (87% vs. 58% at 4 years) and cause-specific survival (80% vs. 64%) compared to radiation therapy with 5-FU alone.

While mitomycin increased the effectiveness of treatment, it was associated with hematologic toxicity as the most common acute side effect, but no long-term toxicity was reported, indicating a favorable safety profile in the context of improved cancer control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a phase 1 study involving 18 patients with locally advanced anal cancer, the combination of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with capecitabine and mitomycin C resulted in a high complete response rate of 83%, indicating strong efficacy in treating this type of cancer.

The maximum tolerated dose of capecitabine was established at 825 mg/m² twice daily, with manageable side effects such as radiation dermatitis and fatigue, suggesting that this treatment regimen is both tolerable and effective for patients.

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]

The combined radiochemotherapy using mitomycin C and 5-fluorouracil showed a high 3- and 5-year survival rate of 79% and a local tumor control rate of 88% and 77%, respectively, in 20 patients with anal carcinoma treated between 1989 and 1994.

While the treatment was generally well tolerated, with only 10% of patients experiencing moderate late effects, the study suggests that combined radiochemotherapy may be superior to radiotherapy alone, supporting its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a study involving three patients with anal canal squamous cell carcinoma, a treatment combining radiotherapy with S-1 and mitomycin C resulted in complete responses without recurrences.

Despite high rates of grade 3 toxicity, including neutropenia and leucopenia in all patients, the treatment was tolerated well, indicating that this regimen is both safe and effective for this type of cancer.

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]