Reduced-Intensity Chemoradiation for Anal Cancer

Recruiting at 710 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: Warfarin, Dilantin

Disqualifiers: Prior radiation, Cardiovascular disease, 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: 5

Duration: 4-6 weeks

252 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well lower-dose chemotherapy plus radiation (chemoradiation) therapy works in comparison to standard-dose chemoradiation in treating patients with early-stage anal cancer. Drugs used in chemotherapy, such as mitomycin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells. This study may help doctors find out if lower-dose chemoradiation is as effective and has fewer side effects than standard-dose chemoradiation, which is the usual approach for treatment of this cancer type.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on warfarin and considering capecitabine, you must switch to a different blood thinner. Also, if you are taking Dilantin for seizures and will receive capecitabine, your Dilantin levels need to be checked weekly.

What data supports the effectiveness of the treatment Reduced-Intensity Chemoradiation for Anal Cancer?

Research shows that using capecitabine, a drug similar to 5-fluorouracil (5-FU), with mitomycin C and radiation therapy is effective for treating anal cancer. Studies have found that capecitabine can replace 5-FU in this treatment, and newer radiation techniques like intensity-modulated radiation therapy (IMRT) may improve outcomes. ^{1 2 3 4 5}

Is reduced-intensity chemoradiation for anal cancer safe for humans?

Studies have shown that treatments using capecitabine, mitomycin-C, and intensity-modulated radiation therapy (IMRT) are generally safe for humans, though they can cause some side effects like gastrointestinal and genitourinary issues. These treatments have been evaluated for anal cancer and other conditions, and while they are considered safe, they may still cause some discomfort or side effects. ^{1 2 3 6 7}

How is the treatment for anal cancer using Capecitabine, Fluorouracil, Intensity-Modulated Radiation Therapy, and Mitomycin different from other treatments?

This treatment is unique because it uses capecitabine, an oral drug, as an alternative to the traditional intravenous 5-fluorouracil (5-FU), combined with mitomycin C and advanced radiation techniques like intensity-modulated radiation therapy (IMRT), which may improve treatment effectiveness and patient convenience. ^{1 3 4 8 9}

Research Team

Jennifer A Dorth

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with early-stage anal cancer (T1-2N0M0) and tumors <=4 cm, who haven't had prior radiation or chemotherapy. HIV-positive patients must have a CD4 count >=300 without lymph node involvement. Participants need good organ function and can't be pregnant or breastfeeding. They should not have other serious illnesses or recent cardiovascular events.

Inclusion Criteria

Patients who are HIV-positive must have A CD4 count >= 300

My anal cancer is early stage, hasn't spread, and the tumor is 4 cm or smaller.

I am willing to switch from warfarin to another blood thinner if I decide to use capecitabine.

Exclusion Criteria

My cancer involves specific lymph nodes near the rectum.

My lymph nodes do not make me ineligible for this study.

Morphologic features of irregular border or central necrosis based on CT / MRI

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard-dose or de-intensified chemoradiation therapy, including mitomycin and either fluorouracil or capecitabine, alongside intensity-modulated radiation therapy (IMRT).

4-6 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 6 weeks, every 3 months for years 1-2, every 6 months for year 3, then annually for years 4-5.

5 years

Multiple visits over 5 years

Treatment Details

Interventions

• Capecitabine
• Fluorouracil
• Intensity-Modulated Radiation Therapy
• Mitomycin

Trial Overview The DECREASE Study is testing whether lower-dose chemoradiation therapy is as effective as the standard dose for treating early-stage anal cancer. It involves drugs like mitomycin, fluorouracil, capecitabine combined with intensity-modulated radiation therapy to see if it reduces side effects while still being effective.

Participant Groups

Group I: Arm B (de-intensified chemoradiation) Experimental Treatment 12 Interventions

Patients undergo 20 or 23 fractions of IMRT. Within 24 hours, patients also receive mitomycin IV over 30 minutes or less on day 1 and either fluorouracil IV over 24 hours on days 1-4 or capecitabine PO BID 5 days per week (Monday - Friday) until completion of IMRT in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/MRI or receive FDG and undergo PET/CT during baseline. Patients undergo CT or MRI on the trial. Patients also undergo tissue biopsy during screening and at the discretion of the treating physician. Additionally, patients undergo blood sample collection throughout the trial.

Group II: Arm A (standard-dose chemoradiation) Active Control 12 Interventions

Patients undergo 28 fractions of intensity-modulated radiation therapy (IMRT). Within 24 hours, patients also receive mitomycin IV over 30 minutes or less on day 1 and either fluorouracil IV over 24 hours on days 1-4 and 29-32 or capecitabine PO BID 5 days per week (Monday - Friday) until completion of IMRT in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/MRI or receive FDG and undergo PET/CT during baseline. Patients undergo CT or MRI on the trial. Patients also undergo tissue biopsy during screening and at the discretion of the treating physician. Additionally, patients undergo blood sample collection throughout the trial.

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?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 11 patients with anal squamous cell carcinoma treated with cisplatin/capecitabine and intensity-modulated radiation therapy, all patients achieved a clinical complete response, indicating high efficacy of this treatment approach.

After a median follow-up of 30 months, there were no local recurrences or distant metastases, and both two-year colostomy-free survival and disease-free survival rates were 100%, demonstrating the safety and effectiveness of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin/capecitabine with intensity-modulated radiation therapy in anal squamous cell carcinoma: a preliminary study. Li, J., Xu, H., Zou, J., et al.[2022]

In a study of 147 anal squamous cell carcinoma patients treated with chemoradiation therapy, capecitabine combined with mitomycin C showed similar overall toxicity levels compared to the standard treatment of 5-fluorouracil and mitomycin C, with no treatment-related deaths reported.

Patients receiving capecitabine experienced significantly less grade 3 hematologic toxicity (4%) compared to those on 5-FU (27%), suggesting that capecitabine may be a safer alternative in terms of blood-related side effects, although further research is needed to fully understand its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity, Tolerability, and Compliance of Concurrent Capecitabine or 5-Fluorouracil in Radical Management of Anal Cancer With Single-dose Mitomycin-C and Intensity Modulated Radiation Therapy: Evaluation of a National Cohort. Jones, CM., Adams, R., Downing, A., et al.[2019]

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]

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]

In a phase 2 trial involving 63 anal cancer patients, dose-painted intensity modulated radiation therapy (DP-IMRT) did not significantly reduce the overall rate of grade 2+ gastrointestinal and genitourinary adverse events compared to conventional treatment, but it did show a notable reduction in grade 3+ gastrointestinal (21% vs. 36%) and dermatologic (23% vs. 49%) toxicities.

DP-IMRT was found to be feasible, but a high rate of pretreatment planning revisions (81%) highlights the need for careful real-time quality assurance in radiation therapy to ensure patient safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Kachnic, LA., Winter, K., Myerson, RJ., 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]

Concurrent chemoradiotherapy (CRT) using 5-fluorouracil (5-FU) and mitomycin C (MMC) remains the standard treatment for anal carcinoma, as recent trials showed that adding induction or maintenance chemotherapy did not improve outcomes.

While cisplatin combined with MMC showed promising response rates in a phase II trial, patient compliance was an issue, indicating that the traditional 5-FU/MMC-CRT regimen is still the most effective and widely used approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined-modality treatment for anal cancer: current strategies and future directions. Fraunholz, I., Rabeneck, D., Weiss, C., et al.[2021]

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]

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

Cisplatin/capecitabine with intensity-modulated radiation therapy in anal squamous cell carcinoma: a preliminary study. [2022]

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

Toxicity, Tolerability, and Compliance of Concurrent Capecitabine or 5-Fluorouracil in Radical Management of Anal Cancer With Single-dose Mitomycin-C and Intensity Modulated Radiation Therapy: Evaluation of a National Cohort. [2019]

4. 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]

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

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

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

RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. [2022]

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

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

8. Germany pubmed.ncbi.nlm.nih.gov

Combined-modality treatment for anal cancer: current strategies and future directions. [2021]

9. 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]