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

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether hypofractionated radiation works to treat patients with Merkel cell carcinoma. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a fewer number of days than tradition radiation therapy courses for Merkel cell carcinoma. This may be less suppressive of the immune response to tumors and should be helpful for patient convenience.

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 data supports the effectiveness of the treatment Hypofractionated Radiation Therapy for Merkel Cell Carcinoma?

Research shows that hypofractionated radiation therapy (HFRT) has been effective in treating various cancers, such as breast cancer and non-small cell lung cancer, by providing similar outcomes to conventional treatments with fewer sessions. This suggests that HFRT could be a promising approach for treating Merkel Cell Carcinoma as well. ^{1 2 3 4 5}

Is hypofractionated radiation therapy generally safe for humans?

Research shows that hypofractionated radiation therapy (HFRT) is generally safe for treating conditions like breast cancer, head-and-neck tumors, and prostate cancer. Studies have found it to be as safe as traditional radiation therapy, with manageable side effects. ^{5 6 7 8 9}

How is hypofractionated radiation therapy different from other treatments for Merkel Cell Carcinoma?

Hypofractionated radiation therapy (HFRT) is unique because it uses fewer, larger doses of radiation over a shorter period compared to traditional radiation treatments. This approach has been shown to be effective in other cancers, like breast and head-and-neck cancers, and may offer a more convenient treatment schedule with similar outcomes. ^{2 4 5 10 11}

Research Team

Devarati Mitra, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

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]

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]

References

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

Phase II study of hypofractionated radiation therapy in elderly patients with newly diagnosed glioblastoma with poor prognosis. [2019]

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

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

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

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Practice of Hypofractionated Radiotherapy in Patients With Invasive Breast Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated radiotherapy is effective and safe for tumors in the head-and-neck. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation treatment in early breast cancer: Results in a New Zealand setting. [2018]

7. United States 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. [2022]

8. England 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. [2022]

9. India pubmed.ncbi.nlm.nih.gov

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy. [2022]

10. Greece pubmed.ncbi.nlm.nih.gov

Limited Toxicity of Hypofractionated Intensity Modulated Radiation Therapy for Head and Neck Cancer. [2022]

11. India pubmed.ncbi.nlm.nih.gov

A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer. [2022]