Imiquimod + Radiation Therapy for Mycosis Fungoides

Overseen By Dermatology Clinical Trials Unit

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Northwestern University

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Nursing, Psychiatric illness, others

Stay on Your Current Meds

No Placebo Group

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

Mycosis fungoides (MF) is the most common subtype of cutaneous T cell lymphoma (MF) and presents as cutaneous patches, plaques, and tumors. Radiation therapy (RT) is a frequently pursued management option for CTCL, especially in patients with more advanced skin disease. Imiquimod stimulates a Th1 lymphocyte response with increased IL-2 and IFN-α, but also induces IFN-α, TNF-α, IL-1α, IL-6, and IL-8, thereby bridging both innate and adaptive immunity. Dosing of both radiotherapy (RT) and imiquimod are based on standard-of-care doses/frequencies for CTCL. The reason imiquimod topical is given for a week before giving RT is to prime innate immune activity for when RT is delivered. It is believed that this serves as an adjuvant for the CD8+ antitumor response generated by RT. 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 conventional (CD4+) MF.

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.

What data supports the effectiveness of the treatment Imiquimod + Radiation Therapy for Mycosis Fungoides?

Research shows that Intensity-modulated radiotherapy (IMRT), a component of the treatment, can deliver high doses of radiation to tumors while minimizing exposure to healthy tissues, which may improve quality of life and treatment outcomes in various cancers. ^{1 2 3 4 5}

Is the combination of Imiquimod and Radiation Therapy generally safe for humans?

Radiation therapy techniques like intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) have been studied for safety in various conditions, showing that while they can cause some side effects, they are generally considered safe with proper planning and safety checks. For example, in prostate cancer treatments, these techniques have been associated with manageable levels of side effects, such as gastrointestinal and genitourinary toxicities. ^{6 7 8 9 10}

How is the treatment of Imiquimod + Radiation Therapy for Mycosis Fungoides different from other treatments?

The combination of Imiquimod (a topical cream that stimulates the immune system) with Radiation Therapy (using high-energy rays to target cancer cells) is unique because it combines a skin-directed immune response with precise radiation, potentially enhancing effectiveness in treating Mycosis Fungoides, especially in cases resistant to other therapies. ^{11 12 13 14 15}

Research Team

Alan Zhou

Principal Investigator

Northwestern University

Eligibility Criteria

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).

Trial Timeline

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

Treatment Details

Interventions

• Imiquimod (Immunomodulator)
• Radiation Therapy (Radiation)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. Netherlands 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? [2022]

3. England pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy for the treatment of pediatric cancer patients. [2006]

4. France pubmed.ncbi.nlm.nih.gov

[Recurrence sites following definitive intensity-modulated conformational radiotherapy of squamous-cell carcinomas of the upper aerodigestive tract]. [2018]

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

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

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

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

Quality and Safety Considerations in Intensity Modulated Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

9. Japan 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. [2018]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

[Five-year results of IMRT for prostate cancer - toxicity]. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Complete resolution of mycosis fungoides tumors with imiquimod 5% cream: a case series. [2018]

12. England pubmed.ncbi.nlm.nih.gov

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

13. Germany pubmed.ncbi.nlm.nih.gov

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

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

Localized conventional radiotherapy in the treatment of Mycosis Fungoides: our experience in 100 patients. [2014]

15. France pubmed.ncbi.nlm.nih.gov

Role of radiation therapy in mycosis fungoides refractory to systemic therapy. [2018]