Chemotherapy + Radiation for HIV-Associated Anal Cancer

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretroviral therapy

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Live vaccines, Autoimmune disease, 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: 10

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the effects of chemotherapy, radiation, and immunotherapy in treating HIV-associated anal cancer. It targets both low-risk and high-risk patients, aiming to kill cancer cells and help the immune system prevent the cancer from coming back.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, participants must be on a stable antiretroviral therapy (ART) regimen for at least 2 weeks before enrollment and should not change it within 12 weeks after enrollment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment for HIV-associated anal cancer?

Research shows that using a combination of chemotherapy drugs like 5-fluorouracil (5-FU) and mitomycin C with radiation therapy can lead to complete remission in many patients with anal cancer, including those who are HIV-positive. Additionally, intensity-modulated radiation therapy (IMRT) can help reduce side effects while maintaining effective treatment. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiation generally safe for treating anal cancer in humans?

The combination of chemotherapy drugs like 5-Fluorouracil (5-FU) and Mitomycin with radiation therapy has been used safely in humans for treating anal cancer, including in HIV-positive patients. However, some patients may experience side effects such as blood-related issues and gastrointestinal problems, especially if they have low immune cell counts. ^{1 2 3 6 7}

How is the treatment of chemotherapy and radiation for HIV-associated anal cancer unique?

This treatment combines chemotherapy drugs like capecitabine and fluorouracil with intensity-modulated radiation therapy (IMRT), which allows for precise targeting of the cancer while sparing healthy tissue, potentially reducing side effects. It is tailored for HIV-positive patients who may experience greater toxicity, with adjustments in chemotherapy dosing and radiation field sizes to improve tolerance and effectiveness. ^{1 2 3 4 8}

Research Team

Rafi Kabarriti

Principal Investigator

AIDS Malignancy Consortium

Eligibility Criteria

This trial is for adults with HIV-associated anal cancer. Low-risk patients have T1-2N0M0 tumors ≤4 cm, while high-risk patients have stage T3-T4N0M0 or T2-4N1M0 tumors. All must understand the study, sign consent, have a life expectancy over 6 months, adequate blood counts and organ function, be on stable HIV treatment with controlled viral load, agree to contraception if applicable, and not be pregnant or breastfeeding.

Inclusion Criteria

My diarrhea is mild or moderate.

I have a specific type of anal cancer that is at a certain stage and has not spread to distant parts of my body.

Participant must have a life expectancy of greater than 6 months

Exclusion Criteria

Uncontrolled intercurrent illness

I need steroids or other drugs that lower my immune system.

My last surgery was more than 4 weeks ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for ECHO, sigmoidoscopy/colonoscopy, anoscopy/proctoscopy, digital rectal exam, CT, and blood sample collection

Treatment (Low-risk stratum)

Patients receive mitomycin IV and either fluorouracil IV or capecitabine PO, along with intensity modulated radiation therapy (IMRT) for 20-23 sessions over 6 weeks

6 weeks

Daily visits for radiation therapy, regular visits for chemotherapy administration

Treatment (High-risk stratum)

Patients receive nivolumab IV every 4 weeks for up to 6 cycles

24 weeks

Visits every 4 weeks for nivolumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 6 weeks, every 3 months for years 1-2, every 6 months for year 3, and annually for years 4-5

Treatment Details

Interventions

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

Trial Overview The trial tests chemotherapy (mitomycin, fluorouracil/capecitabine) combined with intensity-modulated radiation therapy for low-risk anal cancer patients. High-risk patients receive standard care plus nivolumab post-treatment to reduce tumor recurrence risk. Nivolumab is an immunotherapy that may help the immune system fight cancer more effectively.

Participant Groups

Group I: Low-risk stratum (mitomycin Experimental Treatment 17 Interventions

Patients receive mitomycin IV on day 1 and either fluorouracil IV on day 1 or capecitabine PO BID on Monday-Friday until the completion of radiation therapy at the discretion of the treating physician. Patients also undergo IMRT QD for 20-23 treatment sessions over 6 weeks. Patients also undergo digital rectal exam, anoscopy/proctoscopy and CT throughout the study, receive FDG IV and undergo PET/CT, PET/MRI and /or MRI during screening and follow-up as well as blood sample collection during screening and EOT. Some patients undergo lymph node biopsy during screening at the discretion of the treating physician.

Group II: High-risk stratum (nivolumab) Experimental Treatment 10 Interventions

Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO during screening as clinically indicated, sigmoidoscopy/colonoscopy, anoscopy/proctoscopy or digital rectal exam and CT throughout the study as well as blood sample collection during screening and EOT.

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?

National Cancer Institute (NCI)

Lead Sponsor

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]

Squamous cell anal cancer is becoming more common, particularly in individuals with HPV and HIV, and can be effectively treated with chemoradiotherapy, specifically using fluorouracil and mitomycin or cisplatin alongside radiation.

HIV-positive patients may experience increased treatment toxicity, especially with low CD4 counts, necessitating modifications to standard treatment protocols, such as adjusting chemotherapy doses and utilizing intensity-modulated radiation therapy (IMRT) to reduce side effects while maintaining effective tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of anal cancer in the HIV-positive population. Kauh, J., Koshy, M., Gunthel, C., et al.[2007]

In a study of 12 HIV-positive men with anal cancer, a combined treatment of chemotherapy (5-FU and mitomycin C) and radical radiotherapy resulted in a high complete remission rate of 9 out of 11 evaluable patients.

Despite some treatment-related toxicities, the study suggests that radical chemoradiation can be safely administered at conventional doses to HIV-positive patients, with a 2-year survival rate of 60% at a median follow-up of 4.8 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of HIV-associated invasive anal cancer with combined chemoradiation. Cleator, S., Fife, K., Nelson, M., et al.[2019]

In a study of six patients with HIV and invasive anal cancer, two patients achieved durable complete responses with a combination of chemotherapy and pelvic radiotherapy, indicating that this treatment can be effective for those with moderate immunosuppression and early-stage tumors.

However, the study also highlighted the risks, as two patients with more advanced disease died within six months, and moderate to severe skin reactions were common, suggesting that treatment outcomes can vary significantly based on the stage of cancer and the patient's immune status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermoid anal cancer in HIV infected patients. Bottomley, DM., Aqel, N., Selvaratnam, G., et al.[2019]

Combined-modality therapy for anal cancer, which includes radiation therapy and chemotherapy, leads to long-term disease-free survival and preservation of the anal sphincter in most patients.

Intensity-modulated radiation therapy (IMRT) may reduce the side effects associated with traditional chemoradiation, allowing for higher radiation doses in certain cases, which could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy for anal cancer. Czito, BG., Pepek, JM., Meyer, JJ., et al.[2013]

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 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 study involving four HIV-infected patients with anal cancer, treatment with radiotherapy and radiochemotherapy was generally well-tolerated, with only mild to moderate acute reactions observed.

All but one patient completed their treatment as scheduled, indicating that HIV-infected patients can tolerate these cancer therapies without excessive side effects, although long-term outcomes are still under evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low acute toxicity of radiotherapy and radiochemotherapy in patients with cancer of the anal canal and HIV-infection. Höcht, S., Wiegel, T., Kroesen, AJ., et al.[2019]

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

Management of anal cancer in the HIV-positive population. [2007]

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

Treatment of HIV-associated invasive anal cancer with combined chemoradiation. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Epidermoid anal cancer in HIV infected patients. [2019]

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

Intensity-modulated radiation therapy for anal cancer. [2013]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Mitomycin in anal canal carcinoma. [2018]

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

Low acute toxicity of radiotherapy and radiochemotherapy in patients with cancer of the anal canal and HIV-infection. [2019]