Total-Skin Electron Beam Therapy + Brentuximab for Skin Cancer

Overseen By Bouthaina Dabaja, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Systemic anticancer, Strong CYP3A4

Disqualifiers: Neuropathy, Renal impairment, Hepatic impairment, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special type of radiation therapy, combined with the drug brentuximab vedotin (Adcetris), can help control mycosis fungoides, a type of skin cancer. Individuals whose cancer has recurred or not responded to previous treatments might be suitable candidates. Participants will receive radiation to the entire skin surface over two days, along with the experimental drug treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications for this trial?

You may need to stop taking certain medications, especially if they are systemic anticancer agents or treatments for mycosis fungoides or Sezary syndrome. However, if you are on stable doses of topical or systemic steroids, you might be able to continue them after discussing with the Principal Investigator. There is no required washout period for prior therapies, but you should avoid strong CYP3A4 inhibitors or inducers.

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

Research has shown that brentuximab vedotin is generally well-tolerated by patients with CD30-expressing cutaneous T-cell lymphoma, a specific type of skin cancer. In one study, 93% of patients experienced complete disappearance of their cancerous skin lesions, suggesting the treatment is effective and relatively safe.

The FDA has already approved brentuximab vedotin for certain cancers, indicating thorough safety testing in those cases. While this does not guarantee safety for every condition, it provides some reassurance about its overall safety in humans.

In summary, current evidence indicates that brentuximab vedotin is usually well-tolerated and significantly effective in treating certain skin cancers. Clinical trial participants will be closely monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Brentuximab vedotin is unique because it combines an antibody with a drug to specifically target cancer cells. Most treatments for skin cancer involve surgery or general chemotherapy, which can affect healthy cells too. Brentuximab vedotin works differently by linking an antibody to a potent drug, allowing it to directly deliver the drug to the cancer cells, minimizing harm to healthy cells. This targeted approach not only has the potential to be more effective but also could reduce side effects compared to traditional treatments. Researchers are excited about this treatment because it offers a more precise attack on cancer cells, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for mycosis fungoides?

Research has shown that brentuximab vedotin, which participants in this trial may receive, effectively treats certain skin cancers, specifically CD30-expressing cutaneous T-cell lymphoma (CTCL). Studies have found that this treatment leads to better results compared to other options. For instance, one study showed that 54.7% of patients responded well to brentuximab vedotin, significantly higher than the 12.5% response rate with standard treatments. This drug targets specific cancer cells and delivers a substance that can kill them. It is approved for use when other treatments have already been tried. ^{1 2 4 5 6}

Who Is on the Research Team?

Bouthaina S. Dabaja

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory mycosis fungoides, a type of skin lymphoma. Participants must have at least 1% CD30 expression in their cancer cells and be stable on certain medications if needed. HIV+ patients can join if treated and with a CD4 count >200. People are excluded if they have severe kidney or liver issues, another primary malignancy treatment, grade 2+ neuropathy, or women not using birth control.

Inclusion Criteria

No required wash-out period for prior therapies

Ability to understand and willingness to sign a written informed consent document

I am on a stable dose of steroids, and stopping them might cause harm.

Exclusion Criteria

My kidney function is severely impaired.

I do not have any serious illnesses that would affect my treatment.

Receipt of systemic therapy for another primary malignancy (other than T-cell lymphoma) after discussion with Principal Investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive ultra-low-dose total-skin electron beam therapy over 2 days

2 days

2 visits (in-person)

Treatment

Participants receive brentuximab vedotin quarterly over 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Ultra-Low-Dose Total-Skin Electron Beam Therapy

Trial Overview The study tests ultra-low-dose total-skin electron beam therapy (ULD-TSEBT) combined with brentuximab vedotin to see its effectiveness against mycosis fungoides over a year. There's no wait time after previous cancer treatments before starting this trial.

How Is the Trial Designed?

Group I: Brentuximab vedotin Experimental Treatment 1 Intervention

Participant will receive radiation therapy to the entire skin surface over the course of 2 days. Each dose will take about 60 to 90 minutes and will vary from one patient to another

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Published Research Related to This Trial

In a study of 434 epithelial skin cancers treated with electron beam therapy, both 54 Gy in 18 fractions and 44 Gy in 10 fractions showed high local recurrence-free rates, with 3-year rates of 97.6% and 96.9% for basal cell carcinomas (BCC) respectively, indicating the efficacy of both treatment schedules.

The 44 Gy in 10 fractions schedule is recommended as the preferred option due to its similar effectiveness and greater convenience for patients, while maintaining a cancer-specific survival rate of 100% for BCC and 98% for squamous cell carcinomas (SCC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a hypofractionated schedule in electron beam radiotherapy for epithelial skin cancer: Analysis of 434 cases. van Hezewijk, M., Creutzberg, CL., Putter, H., et al.[2018]

The combination of low-dose total skin electron beam therapy (LD-TSEBT) and mogamulizumab was well-tolerated and led to global complete responses in two patients with refractory Sézary syndrome, despite their previous treatments failing.

Both patients achieved significant clinical improvement, with one responding in 4 weeks and the other in 9 weeks, and maintained their complete responses for up to 72 weeks, suggesting this combination could be an effective treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Total Skin Electron Beam Therapy Combined With Mogamulizumab for Refractory Mycosis Fungoides and Sézary Syndrome. Fong, S., Hong, EK., Khodadoust, MS., et al.[2022]

In a study of 8 patients with oligoprogressive metastatic Merkel cell carcinoma (mMCC) undergoing radiotherapy while on avelumab, the addition of radiotherapy resulted in a high objective response rate of 75% and significantly prolonged progression-free survival (PFS) after treatment, with 60% of patients remaining progression-free at 1 year.

No significant treatment-related toxicities were observed, indicating that combining radiotherapy with immunotherapy is a safe approach for managing limited progression in mMCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance? Ferini, G., Zagardo, V., Critelli, P., et al.[2023]

In a study of 92 patients with locally advanced squamous cell carcinoma of the head and neck, the combination of cetuximab and radiotherapy resulted in significant skin and mucosal toxicities, with 37% of patients experiencing severe dermatitis and 57.6% suffering from severe mucositis.

Despite the treatment's potential benefits, severe toxicities led to frequent interruptions in radiotherapy, which negatively impacted overall survival, highlighting the need for careful management of side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab. Roman, J., Dissaux, G., Gouillou, M., et al.[2018]

Combining external beam radiotherapy (EBRT) with carbon ions and endoradiotherapy using radiolabeled agents, like 131I-Cetuximab, significantly enhances tumor targeting and growth inhibition in cancer models, showing improved uptake of the radiolabeled agents after EBRT.

The combination therapy not only reduced tumor growth more effectively than either treatment alone but also altered gene expression related to DNA repair and immune response, suggesting a promising new approach in precision cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined external beam radiotherapy with carbon ions and tumor targeting endoradiotherapy. Melzig, C., Golestaneh, AF., Mier, W., et al.[2019]

In a study of 10 patients with Stage IB-II mycosis fungoides, low-dose total skin electron beam therapy (4 Gy) resulted in complete responses in 2 patients and partial responses in 6 patients, although the duration of these responses was relatively short, averaging around 2 months.

The treatment was well-tolerated with only mild side effects like skin desquamation and erythema, indicating that it may be a safe option for palliative care in mycosis fungoides, allowing for repeated treatments without severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides. Kamstrup, MR., Specht, L., Skovgaard, GL., et al.[2008]

Modulated electron radiotherapy (MERT) can improve dose distribution for treating shallow tumors while minimizing exposure to surrounding critical organs, using photon multileaf collimators to create narrow segments for electron beams.

The study demonstrated that accurate dose calculations for MERT are feasible with existing technology, achieving excellent agreement between calculated and measured doses, which supports the potential for more effective and conformal radiotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of calculations for electrons modulated with conventional photon multileaf collimators. Klein, EE., Vicic, M., Ma, CM., et al.[2019]

In a study of 389 patients with nonmelanoma skin carcinoma, both electron beam therapy and superficial x-ray therapy showed a low overall local recurrence rate of 4.9%, indicating effective treatment options.

Electron beam therapy provided better cosmetic outcomes compared to superficial x-ray therapy, especially for larger tumors, suggesting it may be the preferred method for treating nonmelanoma skin cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electron beam therapy is not inferior to superficial x-ray therapy in the treatment of skin carcinoma. Griep, C., Davelaar, J., Scholten, AN., et al.[2006]

In a study of 99 head-and-neck cancer patients receiving simultaneous integrated boost intensity-modulated radiotherapy with cetuximab, 34% experienced severe dermatitis (Grade 3/4), significantly higher than the 3% in a control group treated with cisplatin.

There was a clear link between the radiation dose to the skin and the severity of dermatitis in patients receiving cetuximab, indicating that higher radiation exposure increases the risk of severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Studer, G., Brown, M., Salgueiro, EB., et al.[2015]

The combination of the anti-EGFR monoclonal antibody C225 with 125-iodine radiation significantly enhances the inhibition of colorectal cancer cell growth compared to either treatment alone, with a sensitizer enhancement ratio of approximately 1.4.

C225 increases radiation-induced apoptosis and impairs DNA repair mechanisms, as evidenced by lower levels of DNA repair proteins and reduced Akt signaling, suggesting a mechanism for its radiosensitizing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of C225 and 125-iodine seed radiation on colorectal cancer cells. Liu, J., Wang, H., Qu, A., et al.[2021]

Combining carbon ion radiotherapy with CTLA4 inhibition led to complete tumor rejection in a murine model, demonstrating the potential for this approach to induce long-lasting antitumor immunity, even against non-irradiated tumors.

The study revealed that this combination therapy reshapes the immune cell composition within tumors, activating natural killer (NK) cells and enhancing T cell responses, suggesting a systemic immunological effect beyond the irradiated site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbon ion irradiation plus CTLA4 blockade elicits therapeutic immune responses in a murine tumor model. Hartmann, L., Osen, W., Eichmüller, OL., et al.[2022]

The collaboration between dermatologists and oncologists has led to the establishment of supportive oncodermatology clinics, which focus on managing skin toxicities associated with targeted therapies for blood cancers.

A systematic review of various targeted therapies revealed distinct cutaneous adverse event profiles, emphasizing the need for early diagnosis and management to enhance treatment tolerability and patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies. Ransohoff, JD., Kwong, BY.[2018]

In a study of seven melanoma patients undergoing combination therapy with a BRAF inhibitor and radiation, most patients experienced good local responses, indicating the efficacy of this treatment approach.

Severe skin toxicity was observed in only two patients, suggesting that while there is an increased risk of skin reactions, most patients tolerate the combination therapy well, making it a viable option for aggressive melanoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization by BRAF inhibitors. Strobel, SB., Pätzold, S., Zimmer, L., et al.[2018]

Concurrent immunoradiotherapy, combining immune checkpoint inhibitors with radiotherapy, showed a 30% overall response rate in 16 patients with metastatic melanoma who had progressed on nivolumab, with a notable 68.8% response rate in lesions within the radiation fields.

Nivolumab combined with radiotherapy demonstrated a 100% response rate inside the radiation fields, suggesting it may be more effective than ipilimumab in this setting, although some patients experienced grade 3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. Nomura, M., Otsuka, A., Yoshimura, M., et al.[2019]

The identification of driver mutations in tumors has led to the rise of personalized medicine in cancer treatment, allowing for targeted therapies like the BRAF inhibitor vemurafenib, which was approved for metastatic melanoma in 2012.

While targeted treatments are generally well-tolerated, they come with a new range of side effects that healthcare providers must understand and manage to ensure optimal patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of systemic oncological therapies in dermatology. Zimmer, L., Vaubel, J., Livingstone, E., et al.[2012]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36017748/

Brentuximab vedotin in the treatment of cutaneous T-cell ... Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment.

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Real-World Treatment Patterns and Clinical Outcomes With ... Based on the ALCANZA trial, brentuximab vedotin (BV) was FDA-approved in 2017 for the treatment of adult patients with pcALCL or CD30- ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1155/dth/7123954

Clinical Experience With Brentuximab Vedotin in Treating ... Brentuximab vedotin (BV) has been approved for CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2473952921005322

Randomized phase 3 ALCANZA study of brentuximab ... Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% ...

5. takedaoncology.com takedaoncology.com/news/news-releases/back-view-printer-friendly-version-takeda-and-seattle-genetics-announce-positive-data-from-phase-3-alcanza-clinical-trial-of-adcetris-brentuximab-vedotin-for-cd30-expressing-cutaneous-t-cell-lymphoma/

Takeda and Seattle Genetics Announce Positive Data from ... Takeda and Seattle Genetics Announce Positive Data from Phase 3 ALCANZA Clinical Trial of ADCETRIS® (Brentuximab Vedotin) for CD30-Expressing Cutaneous T-Cell ...

6. jaad.org jaad.org/article/S0190-9622(11)01252-7/fulltext

Resolution of malignant cutaneous lesions with ... Complete resolution of malignant cutaneous lesions was achieved in 93% of patients (14/15) with a median time to resolution of all lesions of 4.9 weeks (range, ...