Total-Skin Electron Beam Therapy + Brentuximab for Skin Cancer

Overseen by Bouthaina S. Dabaja

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Systemic anticancer, Strong CYP3A4

Disqualifiers: Neuropathy, Renal impairment, Hepatic impairment, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of low-dose skin radiation and a targeted cancer drug. It focuses on patients with a specific type of skin lymphoma that is hard to treat. The treatment works by using radiation to reduce cancer cells on the skin and a drug to kill them directly.

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.

What data supports the effectiveness of the treatment Total-Skin Electron Beam Therapy + Brentuximab for Skin Cancer?

Research shows that low-dose total skin electron beam therapy is effective in treating skin conditions like mycosis fungoides, and electron beam therapy is comparable to x-ray therapy for skin cancer. This suggests potential effectiveness when combined with Brentuximab, a drug known for its antitumor properties. ^{1 2 3 4 5}

Is Total-Skin Electron Beam Therapy combined with Brentuximab generally safe for humans?

Brentuximab, used in targeted cancer therapies, can cause skin-related side effects that may require changes in treatment. It's important to monitor for these reactions to ensure safety and maintain quality of life during treatment. ^{6 7 8 9 10}

How is the treatment Total-Skin Electron Beam Therapy + Brentuximab Vedotin unique for skin cancer?

Total-Skin Electron Beam Therapy combined with Brentuximab Vedotin is unique because it uses a targeted approach where Brentuximab Vedotin, an antibody-drug conjugate, specifically targets cancer cells expressing CD30, a protein found on some skin cancers, while the electron beam therapy treats the entire skin surface, potentially enhancing the overall effectiveness of the treatment. ^{11 12 13 14 15}

Research Team

Bouthaina S. Dabaja

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

I am 18 years old or older.

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

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

Trial Timeline

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

Treatment Details

Interventions

• Brentuximab Vedotin (Monoclonal Antibodies)
• Ultra-Low-Dose Total-Skin Electron Beam Therapy (Radiation)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

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

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy of a hypofractionated schedule in electron beam radiotherapy for epithelial skin cancer: Analysis of 434 cases. [2018]

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

Low-Dose Total Skin Electron Beam Therapy Combined With Mogamulizumab for Refractory Mycosis Fungoides and Sézary Syndrome. [2022]

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

A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides. [2008]

4. England pubmed.ncbi.nlm.nih.gov

Validation of calculations for electrons modulated with conventional photon multileaf collimators. [2019]

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

Electron beam therapy is not inferior to superficial x-ray therapy in the treatment of skin carcinoma. [2006]

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

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Radiosensitization by BRAF inhibitors. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. [2019]

9. Switzerland 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? [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Side effects of systemic oncological therapies in dermatology. [2012]

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

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. [2015]

12. France 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. [2018]

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

Combined external beam radiotherapy with carbon ions and tumor targeting endoradiotherapy. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Combined effects of C225 and 125-iodine seed radiation on colorectal cancer cells. [2021]

15. Ireland pubmed.ncbi.nlm.nih.gov

Carbon ion irradiation plus CTLA4 blockade elicits therapeutic immune responses in a murine tumor model. [2022]