Imiquimod + Radiation Therapy for Mycosis Fungoides

Overseen By Dermatology Clinical Trials Unit

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Northwestern University

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Nursing, Psychiatric illness, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for mycosis fungoides, a type of skin lymphoma that causes patches, plaques, and tumors on the skin. The study combines a topical cream called imiquimod with radiation therapy to enhance the body's immune response against cancer cells. Researchers aim to determine if this combination is safe and effective for treating the disease. Individuals with confirmed stage IA-IIB mycosis fungoides who have not responded to standard treatments and have multiple skin lesions might be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot be on current systemic or topical CTCL therapy unless you have been stable on it for more than 6 months.

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

Research is examining the safety of combining imiquimod and radiation therapy to treat mycosis fungoides, a type of skin cancer. Imiquimod, a cream, boosts the body's immune system, while radiation therapy directly targets cancer cells. This trial is in its early stages, so limited safety information is available. However, both treatments are already used separately in standard care, suggesting they might work well together. Previous studies have shown that radiation therapy effectively treats mycosis fungoides, yielding good results for various tumor sizes. Since this combination is new, monitoring for side effects is crucial to understanding its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment for mycosis fungoides because it combines imiquimod cream with localized radiation therapy, offering a unique dual approach. Unlike standard treatments like topical corticosteroids or phototherapy, this method uses imiquimod, which boosts the immune system's response right at the tumor site. Additionally, combining this with precise radiation therapy targets lesions more effectively, potentially leading to better outcomes with less overall radiation exposure. This innovative combination has the potential to enhance treatment effectiveness while minimizing side effects.

What evidence suggests that this combination of imiquimod and radiation therapy could be effective for mycosis fungoides?

In this trial, participants will receive a combination of a cream called imiquimod and radiation therapy to treat mycosis fungoides, a type of skin cancer. Research has shown that imiquimod helps the immune system fight cancer cells, and early results suggest it can enhance the effectiveness of radiation therapy. Radiation therapy alone is already very effective, with up to 95% of smaller skin tumors completely responding. This combination aims to improve these results by using the immune system to target the cancer more effectively. ^{1 2 3 4 6}

Who Is on the Research Team?

Alan Zhou

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-90 with confirmed stage IA-IIB mycosis fungoides, a type of skin lymphoma. They should have tried at least one standard treatment without success and have stable disease for over six months. Participants need multiple distinct lesions and must understand and consent to the study.

Inclusion Criteria

I have tried at least one standard treatment for myelofibrosis without success.

My condition has been stable for more than 6 months.

My condition is early-stage mycosis fungoides (stage IA-IIB).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical imiquimod for 6 weeks, with radiation therapy administered during the second week

6 weeks

Weekly visits for imiquimod application and radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including microbiome and immune response assessments

6 weeks

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Imiquimod
• Radiation Therapy

Trial Overview The trial tests combining a cream called Imiquimod with local radiotherapy on skin lesions caused by mycosis fungoides. The idea is that the cream boosts the body's immune response which may help make the radiation treatment more effective against this skin cancer.

How Is the Trial Designed?

Group I: Topical IMQ and localized RT Experimental Treatment 2 Interventions

After the initial study visit, patients will immediately begin use of imiquimod cream at designated lesions (those with combined size \>50cm2) nightly for 5 consecutive days a week over 6 weeks. One week into the imiquimod treatment course, radiation therapy will be administered at Northwestern Medicine by radiation oncologists familiar with MF in 2 fractions of 4 Gy (total 8 Gy) over 2 days to the same designated lesions.

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

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

Intensity-modulated radiation therapy (IMRT) can deliver higher doses of radiation to tumors while minimizing exposure to surrounding healthy tissues, which is particularly important in pediatric patients.

Although IMRT has been successfully used in various adult cancers, its application in children is still limited, highlighting the need for further research and exploration of its potential benefits and challenges in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy for the treatment of pediatric cancer patients. Rembielak, A., Woo, TC.[2006]

Local radiation therapy has been found to be an effective and tolerable treatment option for patients with relapsed or resistant early-stage mycosis fungoides (MF), particularly when other systemic therapies, like bexarotene, have failed.

This approach is not only efficient but also cost-effective, highlighting its potential as a viable alternative in the management of early-stage MF, where treatment options can vary widely based on individual patient factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radiation therapy in mycosis fungoides refractory to systemic therapy. de Sanctis, V., Persechino, S., Fanelli, A., et al.[2018]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

Whole-skin electron therapy is highly effective for treating mycosis fungoides, achieving complete remission in 93% of cases when administered at doses over 30 Gy, compared to only 18% remission with doses under 10 Gy.

Combining whole-skin electron therapy (30 Gy) with chemotherapy or total lymphoid irradiation (30 Gy) offers a promising new treatment strategy for advanced stages of this malignant T-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Whole-skin electron therapy: a therapeutic concept for mycosis fungoides and Sézary syndrome. 2: Therapy]. Herbst, M.[2006]

Intensity Modulated Radiation Therapy (IMRT) is now the primary technique for delivering radiation treatment, allowing for higher doses to be targeted precisely while protecting surrounding healthy tissue.

The updated consensus emphasizes the importance of quality and safety in IMRT planning and delivery, requiring a team-based approach and comprehensive quality assurance programs to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Intensity Modulated Radiation Therapy: An ASTRO Safety White Paper Update. Moran, JM., Bazan, JG., Dawes, SL., et al.[2023]

Topical 5% imiquimod cream demonstrated complete resolution of mycosis fungoides (MF) tumors in two stage IIB patients, with no recurrence observed over follow-up periods of 8 years and 2 years, respectively.

Imiquimod may serve as an effective alternative to localized radiation for treating isolated MF tumors, although some patients may experience mild adverse effects like application site irritation and flu-like symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete resolution of mycosis fungoides tumors with imiquimod 5% cream: a case series. Lewis, DJ., Byekova, YA., Emge, DA., et al.[2018]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

Intraoperative radiotherapy (IORT) for early-stage breast cancer significantly improves radiation-related quality of life (QoL) parameters, with patients reporting less pain and better functioning compared to those receiving external beam radiotherapy (EBRT).

In a study of 230 women, those treated with IORT alone experienced fewer breast and arm symptoms and better overall role functioning, indicating that IORT may be a more patient-friendly option than traditional EBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. Welzel, G., Boch, A., Sperk, E., et al.[2021]

Intensity-modulated radiotherapy (IMRT) significantly improves quality of life (QoL) for patients with head and neck cancers compared to traditional two-dimensional radiotherapy (2DRT) and three-dimensional conformal radiotherapy (3DCRT), particularly in areas like dry mouth and eating-related difficulties.

The review included 14 studies, highlighting that while IMRT shows promise for enhancing QoL, further prospective randomized studies are needed to confirm its benefits and justify the additional resources required for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy versus conventional and 3D conformal radiotherapy in patients with head and neck cancer: is there a worthwhile quality of life gain? Tribius, S., Bergelt, C.[2022]

In a study of 167 patients with head and neck squamous cell carcinoma, the locoregional control rates for cancer were 87.9% at 1 year and 77.6% at 2 years, indicating effective management of the disease with intensity-modulated radiotherapy (IMRT).

The analysis revealed that patients receiving higher doses (70 Gy) had a higher rate of relapse in high-risk areas, while those treated with lower doses (66 Gy and 50 Gy) experienced recurrences outside the irradiated volume, highlighting the importance of dose optimization in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recurrence sites following definitive intensity-modulated conformational radiotherapy of squamous-cell carcinomas of the upper aerodigestive tract]. Yossi, S., El Alouani, C., Pointreau, Y., et al.[2018]

Intensity-modulated radiotherapy (IMRT) has been shown to significantly reduce toxicity-related side effects compared to conventional radiotherapy in various cancers, including head and neck and breast cancers, based on evidence from 61 studies involving over 7,000 patients.

IMRT not only maintains better quality of life by preserving functions like saliva production in head and neck cancer patients but also allows for safer dose escalation in prostate cancer, indicating its efficacy in improving treatment outcomes across multiple tumor sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the clinical evidence for intensity-modulated radiotherapy. Staffurth, J.[2022]

In a retrospective study of 100 patients with Mycosis Fungoides, localized superficial radiotherapy achieved a high complete remission rate of 88%, demonstrating its efficacy as a treatment option.

The treatment was well tolerated with good cosmetic outcomes in 93% of cases, and the local control rate was 85% after 5 years, indicating that localized radiotherapy is both effective and safe for managing this skin condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized conventional radiotherapy in the treatment of Mycosis Fungoides: our experience in 100 patients. Piccinno, R., Caccialanza, M., Çuka, E., et al.[2014]

In a study of 233 men with localized prostate cancer treated with high-dose intensity modulated radiotherapy (IMRT), acute Grade 2 gastrointestinal toxicity occurred in 12.8% of patients, while acute Grade 2 genitourinary toxicity was seen in 18.1%, indicating manageable side effects during treatment.

With a median follow-up of 49.2 months, the 5-year cumulative incidence of Grade 2 gastrointestinal and genitourinary toxicity was 22.4% and 17.7%, respectively, demonstrating that IMRT allows for effective dose escalation while maintaining an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Five-year results of IMRT for prostate cancer - toxicity]. Doležel, M., Odrážka, K., Vaňásek, J., et al.[2019]

A case report highlights that a patient with tumor-stage mycosis fungoides of the scalp had a significant response to a single fraction of palliative radiotherapy.

This suggests that palliative radiotherapy could be an effective treatment option for localized tumor-stage mycosis fungoides, potentially offering a simpler alternative to more complex systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remarkable remission of a tumor-stage mycosis fungoides on the scalp by single fraction palliative radiotherapy. Katano, A.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05838599

Combining Topical Imiquimod With Local Radiotherapy for ... The primary aim of this study is to assess the safety and efficacy of a combination local radiotherapy and topical imiquimod approach for the treatment of ...

2. withpower.com withpower.com/trial/early-phase-1-mycoses-6-2023-21193

Imiquimod + Radiation Therapy for Mycosis Fungoides This Phase < 1 medical study run by Northwestern University is evaluating whether Radiation Therapy will have tolerable side effects & efficacy for patients ...

3. trial.medpath.com trial.medpath.com/clinical-trial/ffd35a6d3723964e/nct05838599-combining-topical-imiquimod-local-radiotherapy-treatment-mycosis-fungoides

Combining Topical Imiquimod With Local Radiotherapy for ... What molecular mechanisms underlie the synergy between imiquimod and radiotherapy in CD4+ mycosis fungoides? ... Outcome data and publication updates.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9563600/

Diagnostic Outcomes and Treatment Modalities in Patients ... At the last follow up, 17 (21%) patients achieved CR, 44 (54%) patients achieved partial responses (PR), 8 (10%) patients achieved stable ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4054991/

The current management of mycosis fungoides and Sézary ... A retrospective study of palliative superficial radiotherapy showed a CR rate of 95% for plaques and small tumors (<3 cm) and a CR rate of 93% for large tumors ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05916

Imiquimod and Local Radiotherapy for Treatment of ... This phase I/II trial tests the safety and side effects of imiquimod and radiation therapy and how well they work in treating patients with mycosis fungoides.