Hypofractionated Radiation Therapy for Merkel Cell Carcinoma

Overseen By Devarati Mitra

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Previous radiation, Distant metastases, Pregnancy, Under 18, 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: 10

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using radiation therapy to treat Merkel cell carcinoma, a rare skin cancer. The treatment, hypofractionated radiation therapy, delivers higher doses of radiation over fewer days than traditional methods. This approach may offer more convenience for patients and better preserve the immune system. Individuals with a confirmed diagnosis of Merkel cell carcinoma, whose cancer has not spread to distant parts of their body, may be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to benefit from innovative care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does allow for immunotherapy at any time, which suggests some flexibility with existing treatments.

What prior data suggests that hypofractionated radiation therapy is safe for treating Merkel cell carcinoma?

Research shows that hypofractionated radiation therapy for Merkel cell carcinoma is generally well-tolerated by patients. Studies comparing this treatment to standard radiation therapy indicate similar effectiveness. Although some studies involved fewer participants, the available data suggests that hypofractionated radiation works as well as regular radiation for treating this type of cancer.

Regarding safety, no strong evidence links major side effects specifically to the hypofractionated approach, suggesting that the treatment is likely safe for most patients. However, since this is a Phase 2 trial, it is important to understand that this phase focuses on further assessing the treatment's effectiveness and checking for any possible side effects. Generally, treatments reaching Phase 2 have already passed initial safety tests in earlier stages. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about hypofractionated radiation therapy for Merkel Cell Carcinoma because it offers a potentially quicker and more convenient treatment schedule. Unlike the standard radiation therapy, which often requires multiple sessions spread over several weeks, this method delivers radiation in just 10 sessions over two weeks. This shorter schedule can significantly reduce the time patients spend undergoing treatment, potentially leading to faster recovery and less disruption to their daily lives. Additionally, the concentrated dosing may enhance the therapy's effectiveness against cancer cells, although this is still being studied.

What evidence suggests that hypofractionated radiation therapy might be an effective treatment for Merkel cell carcinoma?

Research has shown that hypofractionated radiation therapy, which participants in this trial will receive, might work as well as standard radiation therapy for treating Merkel cell carcinoma. One study found that this type of radiation produced results similar to the traditional method. Another study, despite involving a small number of patients, suggested that hypofractionated radiation could be as effective as standard radiation. Early findings also hint that this approach might be even more effective. Overall, the evidence suggests that hypofractionated radiation could be a promising treatment for Merkel cell carcinoma. ^{4 6 7 8 9}

Who Is on the Research Team?

Devarati Mitra, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Merkel Cell Carcinoma (MCC) who've had surgery to remove the tumor or affected lymph nodes within the last 4 months and show no signs of cancer spread. They must be able to consent, use contraception, and have a performance status allowing daily activities with some limitations.

Inclusion Criteria

I am capable of limited self-care.

I had a positive lymph node biopsy and am planning radiation therapy without full lymph node removal.

I had surgery to remove my primary MCC tumor less than 4 months ago and am planning radiation therapy.

Exclusion Criteria

My cancer has spread to distant parts of my body.

I've had radiation before in the same area where my current cancer needs treatment.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients receive hypofractionated radiation therapy in 10 daily fractions (M-F) over 2 weeks

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of local and nodal control rates and disease outcomes

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Radiation Therapy

Trial Overview The study tests if a shorter course of radiation therapy (3.6 Gy x 10 fractions) is as safe and effective as the standard longer course in treating MCC patients, who may also be receiving immunotherapy treatments at any stage.

How Is the Trial Designed?

Group I: Radiation therapy Experimental Treatment 1 Intervention

Patients receive radiation therapy in 10 daily fractions (M-F) over 2 weeks.

Hypofractionated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in European Union as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in Canada as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 3518 breast cancer patients, moderately hypofractionated whole-breast radiotherapy (HFRT) resulted in significantly lower rates of acute dermatitis, breast edema, and hyperpigmentation compared to normofractionated radiotherapy (NFRT), indicating HFRT's safety and efficacy in real-life settings.

HFRT also led to less pain in patients (33.4% vs. 53.7% with NFRT), suggesting it may be a preferable treatment option, especially for patients with higher BMI or larger breast sizes, despite these factors being associated with increased dermatitis risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable safety profile of moderate hypofractionated over normofractionated radiotherapy in breast cancer patients: a multicentric prospective real-life data farming analysis. Issoufaly, I., Petit, C., Guihard, S., et al.[2022]

Hypofractionated radiation therapy (HFRT) at a dose of 52.5 Gy over 15 fractions was found to be feasible and effective for selected elderly patients with newly diagnosed glioblastoma, showing a median overall survival of 8 months and a 12-month overall survival rate of 30%.

The study indicated that HFRT resulted in limited toxicity, with no increase in steroid use during treatment, and some patients even experienced a reduction in steroid requirements, suggesting a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of hypofractionated radiation therapy in elderly patients with newly diagnosed glioblastoma with poor prognosis. Navarria, P., Pessina, F., Cozzi, L., et al.[2019]

In a study of 274 early breast cancer patients treated with hypofractionated radiation treatment (HFRT) over a median follow-up of 7 years, the local recurrence-free survival rate was very high at 97.2%, indicating that HFRT is effective in preventing local cancer recurrence.

The acute toxicity associated with HFRT was generally low, with most patients experiencing less than grade 3 side effects, suggesting that HFRT is a safe treatment option for eligible patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation treatment in early breast cancer: Results in a New Zealand setting. James, ML., Dehn, G., Robinson, BA.[2018]

In a study of 81 patients with localized breast cancer treated with hypofractionated radiotherapy (HFRT), the treatment was well-tolerated, with low rates of late toxicities such as chest pain (11%) and limb pain (12%).

The five-year overall survival rate was 76.5%, and there were no locoregional recurrences, indicating that HFRT is effective in controlling the disease while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy. Sindhu, M., Malik, M., Ahmed, SF., et al.[2022]

Hypofractionated radiation therapy (HypoRT) was found to be effective in treating inoperable advanced non-small cell lung cancer (NSCLC), with an overall response rate of 83% among 30 patients, and a median follow-up of 13 months.

The treatment was well-tolerated, with manageable acute toxicities; however, 37% of patients experienced locoregional recurrence, and 57% developed distant metastasis, indicating the need for further studies to compare HypoRT with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Osti, MF., Agolli, L., Valeriani, M., et al.[2018]

High-dose, hypofractionated radiotherapy (HFRT) demonstrated a high overall response rate of 79% and a one-year local-progression free rate of 50% in treating head-and-neck malignancies, based on a retrospective analysis of 48 patients.

The study found that delivering doses of 6Gray or higher per fraction improved locoregional control, and increased toxicity was not observed with doses of 8Gray or more, suggesting that HFRT can be both effective and safe for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated radiotherapy is effective and safe for tumors in the head-and-neck. Teckie, S., Lok, BH., Rao, S., et al.[2022]

In a study of 1,010 breast cancer patients, hypofractionated radiotherapy (HFRT) showed similar locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) rates compared to conventionally fractionated radiotherapy (CFRT) after a median follow-up of 49.5 months.

While HFRT was effective across various nodal stages and molecular subtypes, it tended to show lower DFS in N2-3 patients with triple-negative breast cancer compared to CFRT, indicating a need for further investigation in this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Practice of Hypofractionated Radiotherapy in Patients With Invasive Breast Cancer. Chen, F., Hui, TSK., Ma, L., et al.[2022]

In a study of 56 patients with head and neck cancers treated with hypofractionated intensity modulated radiation therapy (H-IMRT), the two-year locoregional control rate was 87%, and the median overall survival was 46 months, indicating promising efficacy.

The treatment was well tolerated, with no severe grade 4 or 5 toxicities reported, and only 79% of patients experienced acute grade 2 or 3 toxicity, suggesting that H-IMRT is a safe option for patients with head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Toxicity of Hypofractionated Intensity Modulated Radiation Therapy for Head and Neck Cancer. Mayo, ZS., Ilori, EO., Matia, B., et al.[2022]

In a study of 56 breast cancer patients receiving hypofractionated external beam radiotherapy (HFRT) after mastectomy, the treatment was well tolerated with mild to moderate acute skin toxicity, and no severe hematological toxicity was observed, indicating a favorable safety profile.

HFRT effectively delivered targeted doses to the chest wall while minimizing exposure to surrounding organs, with mean lung and heart doses remaining within safe limits, suggesting that HFRT can be a viable option for post-mastectomy radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer. Deshmukh, S., Sharan, K., Fernandes, DJ., et al.[2022]

Hypofractionated radiation therapy, which delivers fewer but larger doses of radiation over a shorter period, has shown comparable outcomes to conventional radiation in treating breast cancer, suggesting it could be an effective alternative.

Ongoing phase 3 trials are investigating hypofractionated whole breast irradiation and accelerated partial breast irradiation, which may lead to broader acceptance of these methods for early-stage breast cancer, although concerns about patient selection and late toxicity remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation therapy in the treatment of early-stage breast cancer. Freedman, GM.[2021]

In a study involving 160 prostate cancer patients, both hypofractionated radiation therapy regimens (56 Gy in 16 fractions and 67 Gy in 25 fractions) were found to be safe, with manageable levels of acute gastrointestinal and urinary toxicity.

Acute grade ≥2 gastrointestinal toxicity occurred in 26% of patients in the 56 Gy group and 20% in the 67 Gy group, indicating that both treatment schedules are effective options with acceptable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial. Fonteyne, V., Sarrazyn, C., Swimberghe, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39394124/

Hypofractionated versus standard fractionation ... Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation.

2. merkelcell.org merkelcell.org/news-and-publications/2024/la/

Hypofractionated versus standard fractionation radiotherapy ... Although this study had a small number of patients, it suggests that hypofractionated radiation might work as well as standard radiation for MCC ...

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(22)00252-3/fulltext

Characterization of clinical outcomes after shorter course ... (B) Merkel cell carcinoma-specific survival by fractionation status showing two-year rates of 86.6 % and 84.7 % for conventional radiotherapy ...

4. scholarlycommons.baptisthealth.net scholarlycommons.baptisthealth.net/cgi/viewcontent.cgi?article=6835&context=se-all-publications

Hypofractionated versus standard fractionation radiotherapy ... Similarly, there has been some suggestion of increased efficacy with hypofractionated radiation regimens over those using standard fractionation ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S036030162400230X

Hypofractionated Radiotherapy for Merkel Cell Carcinoma Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05100095

Hypofractionated Radiation Therapy for Merkel Cell ... This phase II trial tests whether hypofractionated radiation works to treat patients with Merkel cell carcinoma. Radiation therapy uses high energy x-rays to ...

7. withpower.com withpower.com/trial/phase-3-carcinoma-3-2022-eba92

Hypofractionated Radiation Therapy for Merkel Cell ... This phase II trial tests whether hypofractionated radiation works to treat patients with Merkel cell carcinoma. Radiation therapy uses high energy x-rays ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11468079/

Hypofractionated versus standard fractionation ... Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation.

9. sciencedirect.com sciencedirect.com/science/article/pii/S0167814022002523

Characterization of clinical outcomes after shorter course ... (A) Overall survival by radiation regimen showing two-year rates of 84.4 % and 62.6 % for conventional radiotherapy and hypofractionated radiotherapy cohorts, ...