Node-Sparing Chemo-Radiation for Anal Cancer

(INSPIRE Trial)

Overseen By Kurian Joseph, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AHS Cancer Control Alberta

Disqualifiers: Prior pelvic radiation, Pregnancy, Metastases, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if skipping preventative radiation to the groin is as effective in treating anal cancer as including it. Researchers also aim to assess whether this approach results in fewer side effects and improved quality of life. Participants will receive chemo-radiation treatment, which combines chemotherapy and radiation therapy, with a focus on a smaller radiation target. Individuals with early-stage anal cancer (T1-3 N0 M0) and no groin lymph node involvement may be suitable for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that chemo-radiation treatment, which combines chemotherapy and radiation therapy, is generally well-tolerated. Studies have found that this method effectively controls the disease and helps maintain the function of the anal sphincter, ensuring the muscles at the end of the digestive tract work properly.

In one study, about 70% of patients remained disease-free two years after treatment, indicating effective cancer control over a significant period.

However, some patients may experience side effects. Common side effects include skin irritation, tiredness, and bowel discomfort. Despite these, the treatment is considered safe and is widely used for patients with anal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about this chemo-radiation treatment for anal cancer because it aims to improve outcomes by reducing the radiation target area. Unlike standard treatments that typically involve broader radiation fields, this approach spares the inguinal lymph nodes, potentially minimizing side effects while still using the effective combination of 5-fluorouracil and mitomycin-C. By focusing radiation more precisely, the treatment could offer a better quality of life for patients without compromising the cancer-fighting benefits.

What evidence suggests that this chemo-radiation treatment might be an effective treatment for anal cancer?

Research shows that combined chemotherapy and radiation treatments for anal cancer work well. In this trial, participants will receive chemo-radiation treatment using the drugs 5-fluorouracil (5-FU) and mitomycin-C (MMC). Some studies have shown that such treatments result in 71% to 79% of patients living at least five years after treatment. Additionally, about 73.9% of patients experienced a complete response, meaning their cancer disappeared after treatment. This suggests that chemo-radiation can effectively treat anal cancer, with good long-term results. In this trial, reducing radiation to the groin area might also decrease side effects, potentially improving patients' quality of life. ^{2 6 7 8 9}

Who Is on the Research Team?

Kurian Joseph, MD

Principal Investigator

AHS-CCI

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early-stage anal cancer (T1-3 N0 M0) who haven't had pelvic radiation, chemotherapy, or surgery for it except biopsy. They must be able to consent and have a good performance status. Women can't be pregnant/breastfeeding and must test negative for pregnancy; men agree not to donate sperm. All participants should commit to effective birth control and have no other health issues that could affect the study.

Inclusion Criteria

I am a woman who can have children and have a negative pregnancy test.

My cancer is confirmed to be squamous cell carcinoma.

My scans show no cancer in the groin lymph nodes.

Exclusion Criteria

Pregnancy or lactation

I am a T1N0 patient planning to have my first surgery.

I have had radiation therapy to my pelvic area before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Radiotherapy with concurrent 5-fluorouracil and mitomycin-C combination treatment. Radiotherapy consists of 5400 cGy delivered in 30 fractions over 6 weeks.

6 weeks

Weekly visits for radiotherapy sessions

Follow-up

Participants are monitored for disease-free survival and quality of life. Follow-up includes PET/CT imaging and quality of life assessments.

36 months

Every 3 months for 2 years, then every 6 months for another year

What Are the Treatments Tested in This Trial?

Interventions

• Chemo-Radiation Treatment

Trial Overview The study tests if avoiding groin radiation in patients with normal sentinel node biopsies and PET-CT scans is as effective as preventative groin radiation in treating anal canal cancer. It also examines whether this approach reduces side effects and improves quality of life.

How Is the Trial Designed?

Group I: chemo-radiation treatment Experimental Treatment 1 Intervention

Radiotherapy with concurrent 5-fluorouracil and mitomycin-C combination treatment. Radiotherapy consists of 5400 cGy delivered in 30 fractions over 6 weeks. The investigators will be using the current standard regimen for the study or no change in the current CCI treatment regimen. However, the radiotherapy target will be smaller than current practice since the investigators will be omitting prophylactic inguinal irradiation.

Chemo-Radiation Treatment is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Chemoradiation for:

• Anal cancer
• Rectal cancer
• Colorectal cancer

Approved in United States as Chemoradiation for:

• Anal cancer
• Rectal cancer
• Colorectal cancer

Approved in Canada as Chemoradiation for:

• Anal cancer
• Rectal cancer
• Colorectal cancer

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Published Research Related to This Trial

Volumetric intensity-modulated arc therapy (VMAT) significantly reduced high-grade acute organ toxicity, particularly proctitis, compared to 3-dimensional conformal radiotherapy (3DCRT) in patients with locally advanced anal carcinoma.

VMAT demonstrated superior 2-year locoregional control (100%) and disease-free survival (100%) compared to 3DCRT, which had rates of 80% and 73%, respectively, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Volumetric intensity-modulated arc therapy vs. 3-dimensional conformal radiotherapy for primary chemoradiotherapy of anal carcinoma: Effects on treatment-related side effects and survival. Weber, HE., Dröge, LH., Hennies, S., et al.[2018]

In a study of 20 patients who underwent salvage surgery for anal canal cancer after failing chemoradiotherapy, the 5-year overall survival rate was 37.4%, indicating that surgery can be a viable option for these patients.

The surgery had a morbidity rate of 35% but no postoperative mortality, suggesting that while there are risks involved, the procedure is generally safe and can effectively address persistent or recurrent cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of Surgical Salvage Treatment for Anal Canal Cancer: A Retrospective Analysis with Overview of the Literature. Pesi, B., Scaringi, S., Di Martino, C., et al.[2018]

In a study of 40 patients with early-stage node-negative anal carcinoma, those who underwent surgery followed by reduced-dose chemoradiation (S/CRT) had similar treatment outcomes to those who received standard definitive chemoradiation (CRT), with 5-year locoregional tumor control rates of 97.5% and overall survival rates of 90%.

Both treatment groups experienced comparable levels of acute and late toxicities, and the 5-year colostomy-free survival was 95% in both, suggesting that reduced-dose RT with or without chemotherapy is a safe and effective option for patients who have undergone R0/1 resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative versus definitive chemoradiation in early-stage anal cancer. Results of a matched-pair analysis. Berger, B., Menzel, M., Breucha, G., et al.[2021]

In a study comparing 40 HIV-positive patients on HAART with 81 HIV-negative patients, both groups showed high complete response rates to chemoradiotherapy (CRT), with 92% for HIV-positive and 96% for HIV-negative patients.

However, HIV-positive patients experienced significantly lower local disease control (38% vs. 87%) and higher rates of severe acute toxicity, indicating a need for improved treatment strategies to enhance long-term outcomes for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy. Oehler-Jänne, C., Huguet, F., Provencher, S., et al.[2022]

Chemoradiotherapy (CRT) was effective in treating anal squamous cell carcinoma, with one patient achieving a complete response and two others achieving partial responses despite treatment discontinuation due to adverse effects.

The outcomes varied among patients, with one patient surviving without recurrence for over three years after salvage surgery, while the others succumbed to comorbidities, highlighting the importance of monitoring overall health in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Three cases of anal squamous cell carcinoma treated with chemoradiotherapy]. Someno, Y., Ishikawa, T., Iwata, N., et al.[2015]

In a study of 30 patients with node-negative anal cancer, reducing the radiation dose to uninvolved lymph nodes to 39.6 Gy during chemoradiation was found to be safe and effective, with a 3-year overall survival rate of 90%.

The treatment resulted in a 100% local control rate of lymph nodes and a 93.3% colostomy-free survival rate, with manageable acute toxicities, indicating that this modified protocol could be a promising approach for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced radiation dose for elective nodal irradiation in node-negative anal cancer: back to the roots? Henkenberens, C., Meinecke, D., Michael, S., et al.[2018]

Chemoradiotherapy (CRT) for anal carcinoma in HIV-positive patients receiving antiretroviral therapy was effective, achieving a complete response in 81% of the 21 patients treated, with a 5-year cancer-specific survival rate of 75%.

Despite some acute toxicity and a significant drop in CD4 counts post-treatment, the immunologic parameters returned to baseline levels with follow-up, indicating that CRT can be safely administered without dose reductions in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for invasive anal carcinoma in human immunodeficiency virus-positive patients receiving highly active antiretroviral therapy. Fraunholz, I., Weiss, C., Eberlein, K., et al.[2022]

In a study of 100 patients undergoing chemoradiotherapy for localized anal cancer, patient-reported outcomes (PROs) indicated a higher incidence of acute toxicity compared to physician-assessed toxicity (CTCAE), highlighting the importance of incorporating PROs in evaluating treatment effects.

Proton therapy demonstrated superior dosimetric planning compared to IMRT and VMAT, suggesting it may reduce radiation exposure to surrounding healthy tissues, potentially leading to lower toxicity in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization. Kronborg, C., Serup-Hansen, E., Lefevre, A., et al.[2019]

In a study of 223 patients with anal squamous cell carcinoma treated with chemoradiotherapy, 48% experienced high-grade acute organ toxicity (HGAOT), primarily dermatitis, which was linked to significantly better disease-free survival rates.

High-grade acute hematologic toxicity (HGAHT) did not show a correlation with improved outcomes, indicating that HGAOT may serve as an independent prognostic factor for better oncological results after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute organ toxicity correlates with better clinical outcome after chemoradiotherapy in patients with anal carcinoma. Martin, D., Rödel, F., von der Grün, J., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3521268/

Long-Term Outcomes of Chemoradiation for Anal Cancer ... The aim of this study was to evaluate long-term oncologic outcomes after concurrent chemoradiation treatment for anal cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S294981982500010X

Review Optimising chemoradiotherapy in anal cancer It is reassuring that the standard 5-FU/MMC arms in all three trials reported very similar 5-year OS at 78%, 79%, and 71% in the RTOG 98-11, ACT ...

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1333558/full

Analysis of definitive chemo-radiation outcomes in anal ... For chemotherapy, group 1 comprised 23 patients who received 5-FU/Capecitabine with MMC, 17 of them (73.9%) achieved CR. On the other hand, all ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/0284186X.2021.1918763

Treatment outcomes and prognostic factors after ... State-of-the-art chemoradiotherapy for SCCA resulted in excellent outcomes, and improved survival compared with previous national data, with <15% treatment ...

5. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(25)00184-0/fulltext

A Retrospective Cohort Analysis Clinical Outcomes and Toxicity Profile of Chemoradiotherapy in Older Versus Younger Patients With Anal Cancer: A Retrospective Cohort Analysis.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10796166/

Analysis of definitive chemo-radiation outcomes in anal ... Chemoradiation offers a high level of disease control and successfully preserves the anal sphincter (15, 16). Data on the outcomes of anal ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8842324/

Outcomes and Toxicity of 428 Patients Treated at a Single ... In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00213-X/fulltext

short-term results of a phase 2 randomised controlled trial In conclusion, early results from the ACT4 trial indicate there is a high complete clinical response rate at 6 months with reduced-dose ...

9. ecancer.org ecancer.org/en/journal/article/1655-outcomes-of-patients-with-anal-cancer-treated-with-definitive-chemoradiation-a-single-centre-experience

Outcomes of patients with anal cancer treated ... Among the surviving participants, the 2-year disease-free survival rate was found to be more than two-thirds. Approximately 20% of the study ...