Bexarotene + Radiotherapy for Cutaneous T-Cell Lymphoma

Recruiting at 2 trial locations

Overseen By Shamir Geller

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Oral retinoids, Gemfibrozil

Disqualifiers: Anaplastic large cell lymphoma, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 82 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of a vitamin A-based drug called bexarotene and a specialized skin-focused radiation therapy known as Total Skin Electron Beam (TSEB) to treat mycosis fungoides, a common type of cutaneous T-cell lymphoma. The goal is to determine if these treatments are more effective together than individually. The trial seeks participants diagnosed with mycosis fungoides, particularly those with persistent skin symptoms unresponsive to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify that you must stop all current medications, but you cannot take oral retinoid therapy within 3 weeks of starting the study drug. Gemfibrozil is prohibited, and you should avoid strong/moderate CYP3A4 inducers and inhibitors if possible. Systemic steroids are not allowed within two weeks of the first dose, unless approved by the investigator.

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

You may need to stop certain medications before joining the trial. Specifically, you cannot take oral retinoid therapy within 3 weeks of starting the study drug, and you should avoid gemfibrozil and certain other medications that interact with bexarotene. It's best to discuss your current medications with the study team to see if any changes are needed.

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

Research has shown that bexarotene, a type of vitamin A, was tested for safety in people with cutaneous T-cell lymphoma (CTCL). In studies involving 193 patients, bexarotene was generally well-tolerated, though some experienced side effects like higher cholesterol levels and skin reactions.

Studies have found Total Skin Electron Beam (TSEB) radiotherapy to be safe in the short term. This radiation therapy targets only the skin's surface, leaving deeper tissues unaffected. Minor side effects might occur, but they are usually manageable and temporary.

Both treatments have been studied separately and are generally safe for people with CTCL. This trial will combine them to determine if they work better together. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Cutaneous T-Cell Lymphoma, which often involve standalone therapies like topical corticosteroids, phototherapy, or systemic retinoids, the combination of Bexarotene and Total Skin Electron Beam (TSEB) radiotherapy offers a dual approach. Bexarotene is a retinoid that targets specific receptors in cancer cells, potentially reducing tumor growth and spread. When paired with TSEB, which delivers precise radiation to the skin's surface, this combination could enhance effectiveness, potentially achieving faster and more significant reductions in disease severity. Researchers are excited about this treatment because it merges a targeted drug with an advanced radiotherapy technique, possibly offering a more comprehensive attack on the cancer while minimizing damage to healthy tissue.

What evidence suggests that combining bexarotene with TSEB radiotherapy might be an effective treatment for mycosis fungoides?

Research has shown that bexarotene effectively treats all stages of cutaneous T-cell lymphoma (CTCL), with about 45% of patients responding well in clinical trials. Some studies even reported a higher response rate of 80% after 24 weeks of treatment. Bexarotene activates certain proteins that can stop cancer cells from growing. In this trial, participants will receive a combination of bexarotene and total skin electron beam (TSEB) therapy. TSEB effectively targets and kills cancer cells on the skin's surface. Combining bexarotene with TSEB might enhance overall effectiveness against mycosis fungoides, a common type of CTCL, by leveraging the strengths of both treatments. ^{5 6 7 8 9}

Who Is on the Research Team?

Brandon Imber, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with a skin lymphoma called mycosis fungoides (MF) can join this trial. They should be in relatively good health, able to consent, and have an ECOG performance status of 0-2. Participants must not be pregnant, use two forms of contraception if applicable, and cannot have had certain other treatments or conditions that would interfere with the study.

Inclusion Criteria

Baseline mSWAT score of at least 10

My skin cancer is at least stage IB or I have Sézary syndrome, and I haven't had systemic treatments or they didn't work.

I am using stable doses of medications to manage itching.

Exclusion Criteria

Pregnancy

High likelihood of protocol non-compliance (in opinion of investigator)

I have been diagnosed with ALCL or another type of non-Hodgkin lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bexarotene and TSEB radiotherapy. Bexarotene starts at 150 mg daily on Day 1, increasing to 300 mg daily on Day 15. TSEB starts on Day 22 with safety assessment on Day 52.

82 days

Multiple visits for treatment and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of radiation dermatitis and skin response.

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Bexarotene
• Total Skin Electron Beam (TSEB)

Trial Overview The trial is testing the safety and effectiveness of combining bexarotene (a vitamin A-like drug) with TSEB radiotherapy—a type of radiation treatment for the skin—in treating MF. The goal is to see if using both treatments together works better than using them separately.

How Is the Trial Designed?

Group I: Bexarotene Combined With Radiotherapy Experimental Treatment 2 Interventions

Patients will be initiated on bexarotene 150 mg daily on Day 1, with dose increase to 300 mg daily on Day 15. Patients will receive Cycle 1 of TSEB on Day 22 (with 2 Gy given on two consecutive days -Day 22 and 23), with safety assessment on Day 52. Efficacy will first be assessed on Day 52 and then again on Day 82 by global response assessment, including mSWAT. Patients who have less than 70% reduction from baseline mSWAT score will be eligible for subsequent cycles of TSEB (administered as 4 Gy over 2 consecutive days), until mSWAT score reduction of ≥ 70%, and up to a total of 6 cycles. Treatment may continue until disease progression, unacceptable toxicity, recommended termination by treating physician, or termination of the study.

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

Approved in United States as Targretin for:

• Cutaneous T-cell lymphoma

Approved in European Union as Targretin for:

• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a study involving eight patients with cutaneous T-cell lymphoma, bexarotene showed significant efficacy, with 71% of those taking the oral formulation achieving a partial response within an average of 27 days.

Bexarotene was generally well-tolerated, although the oral form caused hypertriglyceridemia in some patients; the topical gel showed long-lasting effects, with one patient maintaining a partial response for 31 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene capsules and gel for previously treated patients with cutaneous T-cell lymphoma: results of the Australian patients treated on phase II trials. Prince, HM., McCormack, C., Ryan, G., et al.[2019]

Bexarotene, an antitumoral agent for cutaneous T-cell lymphoma, has been shown to increase clotting times in both in vitro and in vivo studies, indicating its anticoagulant effects.

The drug primarily inhibits factor IX and factor X without significantly affecting other coagulation factors, suggesting that patients on bexarotene should be monitored for coagulation issues, especially if they have existing deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions of bexarotene (LGD1069, Targretin) with the coagulation system. Hespel, A., Mejdoubi-Charef, N., Yous, S., et al.[2018]

In a pilot trial involving 10 patients with advanced cutaneous T-cell lymphomas, bexarotene showed limited efficacy, achieving only short partial remissions in 2 patients and lasting stabilization in 4 patients, while 4 patients experienced disease progression.

Bexarotene treatment led to significant adverse effects, including hypertriglyceridemia in 6 patients, resulting in therapy suspension for 3 patients, indicating that the risks may outweigh the benefits for standard treatment use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences. Bohmeyer, J., Stadler, R., Kremer, A., et al.[2019]

In a study of 66 patients with advanced cutaneous T-cell lymphoma (CTCL), bexarotene showed an overall response rate of 44%, with 9% achieving complete response and 35% achieving partial response, indicating its efficacy across different stages of the disease.

Bexarotene was well tolerated, with common side effects including central hypothyroidism and hyperlipidaemia, both of which were manageable, suggesting a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene therapy for mycosis fungoides and Sézary syndrome. Abbott, RA., Whittaker, SJ., Morris, SL., et al.[2018]

Bexarotene is an effective treatment for cutaneous T-cell lymphoma, showing over a 50% response rate in patients who did not respond to or could not tolerate previous therapies, based on Phase II/III trials.

While bexarotene can cause side effects like central hypothyroidism and elevated cholesterol, these can be managed, making it a strong candidate for combination therapies with other treatments for cutaneous T-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene: a clinical review. Farol, LT., Hymes, KB.[2018]

Bexarotene, an antitumoral agent, causes hypertriglyceridemia by activating the RXR/LXR heterodimer, which specifically influences lipogenic gene expression in the liver.

The study found that while bexarotene increases triglyceride levels, it does not affect cholesterol homeostasis, indicating a selective action on metabolic pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via gene-specific permissivity of the RXR/LXR heterodimer in the liver. Lalloyer, F., Pedersen, TA., Gross, B., et al.[2021]

In a phase III study involving 50 patients with early-stage cutaneous T-cell lymphoma, topical bexarotene gel 1% showed substantial efficacy, with overall response rates of 44% to 54% depending on the assessment method used.

The treatment was generally well tolerated, with only mild to moderate side effects such as skin irritation and pruritus, and no serious treatment-related adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. Heald, P., Mehlmauer, M., Martin, AG., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11331325/

Bexarotene is effective and safe for treatment of ... - PubMed For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0001731024001601

Experience With Bexarotene to Treat Cutaneous T-Cell ... It has proven to be effective for all stages of CTCL, with an overall response (OR) rate of 45% in clinical trials.9, 10 Hypertriglyceridemia and central ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8941067/

Comparison of the Efficacy and Safety of Bexarotene and ... At 24 weeks after initiating treatment, the total response rate was 80.0% according to the modified Severity-Weighted Assessment Tool (mSWAT) ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2001.19.9.2456

Bexarotene Is Effective and Safe for Treatment of ... For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were ...

5. targretinhcp.com targretinhcp.com/clinical-studies/

Clinical Studies - Targretin When put to the test, TARGRETIN delivered results for all stages of CTCL across 4 clinical studies. Gel offers demonstrated efficacy across stages 1A and 1B.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/021055s006lbl.pdf

Targretin® (bexarotene) capsules, 75 mg - accessdata.fda.gov Targretin capsules were evaluated in 152 patients with advanced and early stage cutaneous T-cell lymphoma (CTCL) in two multicenter, open-label, historically- ...

7. ema.europa.eu ema.europa.eu/en/documents/product-information/targretin-epar-product-information_en.pdf

Targretin, INN-bexarotene - European Medicines Agency The safety of bexarotene has been examined in clinical studies of 193 patients with CTCL who ... cutaneous T-cell lymphoma (CTCL) whose disease has not responded ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/bexarotene-oral-route/description/drg-20067969

Bexarotene (oral route) - Side effects & dosage Bexarotene belongs to the group of medicines known as retinoids. It is used to treat a certain type of cancer called cutaneous T-cell lymphoma.

9. targretinhcp.com targretinhcp.com/

Targretin TARGRETIN (bexarotene) gel is indicated for the topical treatment of cutaneous lesions in patients with cutaneous T-cell lymphoma, CTCL (Stage 1A and 1B)