Radiation Therapy for Dupuytren's Contracture

Overseen By Lance Warhold, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dartmouth-Hitchcock Medical Center

Disqualifiers: Pregnancy, Neuromuscular disorders, others

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: 1

Duration: 12-14 weeks

95 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to learn about preventing recurrence of Dupuytren's Contracture. The main question it aims to answer are: • Does targeted radiation therapy decrease recurrence of Dupuytren's contracture after treatment with Collagenase Clostridium Histolyticum? Participants will undergo: * Release of Dupuytren's Contracture after Collagenase Clostridium Histolyticum injection * Daily radiation therapy treatment for 5 days followed by 6-8 week rest period and then another course of 5 days of radiation therapy

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this treatment for Dupuytren's Contracture?

Research on intraoperative radiotherapy (IORT) shows it can effectively deliver high doses of radiation directly to the tumor bed, reducing recurrence in breast cancer patients. While this is not directly related to Dupuytren's Contracture, it suggests that targeted radiation can be effective in treating localized conditions. ^{1 2 3 4 5}

Is radiation therapy generally safe for humans?

Radiation therapy techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) have been used in various treatments, showing some risks of side effects such as gastrointestinal and genitourinary issues, but these are generally low. Advances in technology have improved safety, making these techniques common in clinical practice. ^{6 7 8 9 10}

How does radiation therapy differ from other treatments for Dupuytren's contracture?

Radiation therapy is unique for Dupuytren's contracture as it aims to prevent the progression of the disease in its early stages, unlike other treatments that may focus on surgical intervention after significant contracture has developed. It involves using targeted radiation to stop the disease from worsening, which is not a standard approach for this condition. ^{11 12 13 14 15}

Research Team

Lance Warhold, MD

Principal Investigator

Dartmouth Health

Eligibility Criteria

This trial is for individuals over 45 with Dupuytren's Contracture (DC) who can't lay their finger and palm flat on a table due to the condition. It's open to those who've had non-surgical release using Collagenase Clostridium Histolyticum, but only for the first two joints treated. Post-menopausal women or those using contraception can join.

Inclusion Criteria

Only my first two joints treated with CCH injections will be considered.

I am 45 years old or older with ductal carcinoma.

I cannot fully straighten my arm or leg.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Collagenase Clostridium Histolyticum injection and release followed by two 5-day courses of radiation therapy separated by a 6-8 week rest period

12-14 weeks

Follow-up

Participants are monitored for recurrence of Dupuytren's Contracture and radiation toxicity

36 months

Visits at 1 month, 6 months, 12 months, 24 months, and 36 months post-radiation treatment

Treatment Details

Interventions

• Radiation Therapy

Trial Overview The study tests if targeted radiation therapy can prevent Dupuytren's contracture from coming back after treatment with an enzyme injection. Participants will receive daily radiation treatments for five days, rest for 6-8 weeks, then have another five-day course of radiation.

Participant Groups

Group I: Patients with Dupuytren's Contacture Experimental Treatment 1 Intervention

Patients with Dupuytren's Contacture will undergo Collagenase Clostridium Histolyticum injection and release followed by two 5-day courses of radiation therapy separated by 6-8 weeks. They will then be followed for 3 years for recurrence.

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?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Findings from Research

Intraoperative radiotherapy (IORT) was used in a study involving 1367 patients with 1400 tumors, showing a 5-year local recurrence rate of 5.98% for those receiving IORT only, which is comparable to other IORT studies but higher than standard whole breast radiation therapy (WBRT).

IORT offers benefits such as convenience and low complication rates, making it a viable option for patients meeting specific criteria, although the addition of WBRT was found to significantly reduce the risk of local recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT). Silverstein, MJ., Epstein, MS., Chen, P., et al.[2022]

Intraoperative radiotherapy (IORT), specifically electron intraoperative therapy (ELIOT), has been successfully used in over 1000 patients for early-stage breast cancer, demonstrating its feasibility as a primary radiation treatment.

The effectiveness of ELIOT relies on advanced technology and a well-coordinated multidisciplinary team, highlighting the importance of quality assurance and staff training in its implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative electron beam radiotherapy (ELIOT) to the breast: a need for a quality assurance programme. Orecchia, R., Ciocca, M., Tosi, G., et al.[2006]

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]

The HDR-IORT-DP technique, used in 16 patients with recurrent cancers, demonstrated feasibility and safety, with 75% achieving negative surgical margins and no severe grade 4+ toxicities reported.

The technique showed promising local control rates of 80% at 2 years, although overall survival was lower at 20%, indicating potential effectiveness in managing locally advanced or recurrent tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative high-dose-rate brachytherapy using dose painting technique: evaluation of safety and preliminary clinical outcomes. Morikawa, LK., Zelefsky, MJ., Cohen, GN., et al.[2018]

Radiation therapy is crucial in breast cancer treatment, significantly reducing local recurrence and improving survival rates, especially with advancements in techniques since the late 1980s.

Shorter courses of radiation therapy (3-4 weeks) are generally as effective as longer ones, and modern techniques like volumetric modulated arc therapy (VMAT) help minimize complications while enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of radiotherapy techniques in breast conservation treatment. Boyages, J., Baker, L.[2020]

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 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]

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]

Image-guided radiotherapy (IGRT) can lead to significant additional radiation exposure for patients, with kV-CBCT delivering a median dose of around 30 mGy to the pelvis, while 2D-kV imaging provides the lowest dose at less than 1 mGy per image pair.

Optimizing imaging protocols can substantially reduce radiation doses, potentially decreasing exposure by up to a factor of 10, highlighting the importance of tailored imaging strategies based on patient anatomy and treatment goals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monte Carlo-based software for 3D personalized dose calculations in image-guided radiotherapy. Le Deroff, C., Berger, L., Bellec, J., et al.[2022]

In a study of 58 patients receiving high-dose radiation therapy for prostate cancer, using gold markers for image-guided radiation therapy (IGRT) reduced residual positioning errors, particularly in the vertical direction.

Despite the reduction in positioning errors with gold markers, the overall differences in dose distributions were moderate, suggesting that daily megavoltage CT (MVCT) alone could be a sufficient and valid alternative for IGRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric implications of inter- and intrafractional prostate positioning errors during tomotherapy : Comparison of gold marker-based registrations with native MVCT. Wust, P., Joswig, M., Graf, R., et al.[2022]

In a study of 129 patients with Dupuytren's contracture, both radiotherapy treatment concepts (30 Gy in 10 sessions vs. 21 Gy in 7 sessions) effectively reduced symptoms and prevented disease progression, with no significant differences in efficacy between the two groups after 1 year.

Acute toxicity was minimal, with only 38% of hands experiencing mild skin reactions, and chronic side effects were low, indicating that both treatment regimens are well-tolerated for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Optimization of radiotherapy in Dupuytren's disease. Initial results of a controlled trial]. Seegenschmiedt, MH., Olschewski, T., Guntrum, F.[2019]

Radiotherapy (RT) effectively prevents disease progression in early-stage Dupuytren's contracture, with 92% of patients remaining stable and 75% showing objective symptom reduction at 3 months follow-up after treatment.

In long-term follow-up (mean 6 years), only 11% of cases progressed, indicating that RT can significantly delay or avoid the need for surgery in patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for prevention of disease progression in early-stage Dupuytren's contracture: initial and long-term results. Keilholz, L., Seegenschmiedt, MH., Sauer, R.[2019]

In a study involving 129 patients with Dupuytren's contracture, both prophylactic radiotherapy (RT) regimens (30 Gy in 10 sessions vs. 21 Gy in 7 sessions) were found to be equally effective in reducing symptoms and preventing disease progression over a 1-year follow-up period.

Acute toxicity from the treatments was minimal, with only slight differences in skin reactions between the two groups, indicating that both RT approaches are well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy optimization in early-stage Dupuytren's contracture: first results of a randomized clinical study. Seegenschmiedt, MH., Olschewski, T., Guntrum, F.[2019]

Radiotherapy effectively prevents disease progression in early-stage Dupuytren's contracture, with 92% of patients remaining stable and 75% showing a reduction in symptoms after 3 months, based on a study of 96 patients over a follow-up period averaging 6 years.

In long-term follow-up, only 11% of cases progressed, indicating that radiotherapy can significantly delay the need for surgical intervention, and any progression can often be managed with additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy in the early stage of Dupuytren's disease. The indications, technic and long-term results]. Keilholz, L., Seegenschmiedt, MH., Born, AD., et al.[2019]

In a study of 62 patients with Dupuytren contracture treated with conventional semi-deep radiotherapy, 98% experienced a halt in the disease progression after a minimum follow-up of 18 months.

85% of patients showed significant improvement, including regression of symptoms like tubercles and cords, while only one patient had a recurrence at the edge of the treated area, indicating the treatment's efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dupuytren's contracture. Radiotherapy in the early stages]. Herbst, M., Regler, G.[2009]

References

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

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT). [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Intraoperative electron beam radiotherapy (ELIOT) to the breast: a need for a quality assurance programme. [2006]

3. 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]

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

Intraoperative high-dose-rate brachytherapy using dose painting technique: evaluation of safety and preliminary clinical outcomes. [2018]

5. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Evolution of radiotherapy techniques in breast conservation treatment. [2020]

6. 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]

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 Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Monte Carlo-based software for 3D personalized dose calculations in image-guided radiotherapy. [2022]

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

Dosimetric implications of inter- and intrafractional prostate positioning errors during tomotherapy : Comparison of gold marker-based registrations with native MVCT. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[Optimization of radiotherapy in Dupuytren's disease. Initial results of a controlled trial]. [2019]

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

Radiotherapy for prevention of disease progression in early-stage Dupuytren's contracture: initial and long-term results. [2019]

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

Radiotherapy optimization in early-stage Dupuytren's contracture: first results of a randomized clinical study. [2019]

14. Germany pubmed.ncbi.nlm.nih.gov

[Radiotherapy in the early stage of Dupuytren's disease. The indications, technic and long-term results]. [2019]

15. Germany pubmed.ncbi.nlm.nih.gov

[Dupuytren's contracture. Radiotherapy in the early stages]. [2009]