Chemotherapy + Radiation for HIV-Associated Anal Cancer

Recruiting at 16 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of combining chemotherapy and radiation for individuals with HIV-associated anal cancer. For low-risk cancer, the trial tests chemotherapy drugs such as mitomycin and capecitabine alongside radiation. In high-risk cases, after standard treatment, the trial adds nivolumab, an immunotherapy drug that enhances the immune system's ability to fight cancer. Suitable candidates for this trial include those living with HIV, diagnosed with either low-risk or high-risk anal cancer, and who have not undergone extensive cancer surgeries. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant advancements in cancer care.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that nivolumab is safe for people with HIV, similar to those without HIV who have cancer. Patients with HIV did not experience more side effects than expected, and there was no increase in virus activity, which is a positive outcome.

Research indicates that the combination of chemotherapy and radiation (using drugs like mitomycin, fluorouracil, capecitabine, and a type of radiation called IMRT) is generally well-tolerated. People with anal cancer had similar results whether they used capecitabine and mitomycin or fluorouracil and mitomycin. Both combinations proved effective and manageable for patients.

In summary, studies suggest that both nivolumab and the chemo-radiation treatments are safe for patients with HIV. These treatments might be suitable for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HIV-associated anal cancer because they bring a fresh approach compared to standard treatments. The high-risk stratum includes nivolumab, an immunotherapy drug that enhances the body's immune response to fight cancer, which is a different mechanism compared to traditional chemotherapy. For the low-risk group, the combination of mitomycin with either fluorouracil or capecitabine, alongside advanced Intensity-Modulated Radiation Therapy (IMRT), aims to target tumors more precisely, potentially reducing side effects and improving outcomes compared to standard radiation. These strategies represent a significant leap forward in treating this condition by integrating immunotherapy and advanced radiation techniques.

What evidence suggests that this trial's treatments could be effective for HIV-associated anal cancer?

Research has shown that chemotherapy combined with radiation therapy effectively treats anal cancer. In this trial, participants in the low-risk stratum will receive mitomycin with either capecitabine or fluorouracil (5-FU) alongside radiation therapy. This combination has proven effective and tends to be safer than other chemotherapy options. Participants in the high-risk stratum will receive nivolumab, an immunotherapy drug that helps the immune system fight cancer cells. Nivolumab has shown promise in managing cancer in HIV-positive patients with high-risk anal cancer by slowing tumor growth and spread. These treatments aim to better control the cancer and prevent its return. ^{2 3 5 6 7}

Who Is on the Research Team?

Rafi Kabarriti

Principal Investigator

AIDS Malignancy Consortium

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10528380/

Capecitabine/Mitomycin versus 5-Fluorouracil/Mitomycin in ... Conclusion: Capecitabine/mitomycin in combination with SIB RapidArc radiation therapy for anal cancer seems as effective as 5-FU-based chemotherapy and is well ...

2. redjournal.org redjournal.org/article/S0360-3016(24)00565-0/abstract

Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ ... HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04929028

UCSF Anal Cancer Trial → Therapy Adapted for High Risk ... This phase II trial studies the side effects of chemotherapy and intensity modulated radiation therapy in treating patients with low-risk HIV-associated anal ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301624005650

Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ ... HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status.

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)39722-2/fulltext

P-341 Capecitabine/mitomycin versus 5-fluorouracil ... Capecitabine associated with mitomycin and SIB-IMRT is a treatment as effective and safer than 5-FU-based chemotherapy for locally SCCAC. Legal entity ...

6. mountsinai.org mountsinai.org/clinical-trials/therapy-adapted-for-high-risk-low-risk-hiv-associated-anal-cancer

Therapy Adapted for High Risk and Low Risk HIV ... Summary: This phase II trial studies the side effects of chemotherapy and intensity modulated radiation therapy in treating patients with low-risk ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04166318

NCT04166318 | Lower-Dose Chemoradiation in Treating ... Patients undergo 28 fractions of intensity-modulated radiation therapy (IMRT). Within 24 hours, patients also receive mitomycin IV over 30 minutes or less on ...