Combined Therapies for Recurrent Brain Cancer

Recruiting at 8 trial locations

Overseen By Christa Seligman

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Monteris Medical

Must not be taking: Bevacizumab

Disqualifiers: More than 3 lesions, Concurrent malignancies, Serious infection, 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: 3 months

261 Participants Needed

Trial Summary

What is the purpose of this trial?

Randomized, post-market multi-center study investigating the efficacy of two sets of treatment algorithms in brain metastases (BM) patients at the time of first intervention for radiographic progression after stereotactic radiosurgery (SRS), with or without surgery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used bevacizumab within 4 weeks of starting the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of this treatment for recurrent brain cancer?

Research shows that radiotherapy, including stereotactic radiosurgery and reirradiation, can improve survival and quality of life for patients with recurrent brain metastases, with minimal side effects. These treatments are effective in controlling local brain disease and are considered safe options for managing relapsing brain conditions. ^{1 2 3 4 5}

Is the combined therapy for recurrent brain cancer generally safe for humans?

Image-guided radiation therapy (IGRT) and intensity-modulated radiotherapy (IMRT) are generally considered safe, with some risk of side effects like gastrointestinal and genitourinary issues. The safety of these therapies has been a focus of research, and they are commonly used in clinical practice. ^{3 6 7 8 9}

How is the treatment of radiation therapy unique for recurrent brain cancer?

Radiation therapy for recurrent brain cancer is unique because it uses advanced techniques like stereotactic radiotherapy (SRT) and intensity-modulated radiation therapy (IMRT) to precisely target tumors, minimizing damage to healthy brain tissue. This approach allows for a second course of radiation, which is not standard, offering a potential option for patients with recurrent tumors. ^{3 10 11 12 13}

Eligibility Criteria

This trial is for adults over 18 who've had brain metastases treated with SRS at least 3 months ago. They must be stable on low-dose steroids, able to undergo biopsy and laser therapy, and commit to the study's follow-up. Women of childbearing age need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

I am 18 years old or older.

I've been stable for 3 days on a low steroid dose.

I had my initial SRS treatment for the target lesion over 3 months ago.

Exclusion Criteria

My cancer outside the brain is quickly getting worse.

I do not have any serious infections or other major health issues.

Patients unable to comply with study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Laser Interstitial Thermal Therapy (LITT) and best medical management with steroids or hypofractionated radiation therapy (RT) for recurrent brain metastases

3 months

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

24 months

Post-op visit, 1 month visit, and subsequent follow-up visits until study exit or 24 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Laser Interstitial Thermal Therapy
• Radiation Therapy
• Steroid Therapy

Trial Overview The REMASTer trial compares two treatment strategies after initial SRS for brain metastases: Radiation Therapy versus Laser Interstitial Thermal Therapy combined with Steroid Therapy. It's randomized, meaning patients are put into groups by chance.

Participant Groups

Group I: Recurrent Tumor Experimental Treatment 2 Interventions

Receives Laser Interstitial Thermal Therapy (LITT) followed by surveillance or Receives Laser Interstitial Thermal Therapy (LITT) followed by hypofractionated radiation therapy (RT).

Group II: Radiation Necrosis Experimental Treatment 2 Interventions

Receives Laser Interstitial Thermal Therapy (LITT) and best medical management with steroids or Receives best medical management with steroids.

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?

Monteris Medical

Lead Sponsor

Trials

10

Recruited

1,600+

Findings from Research

The review discusses various treatment options for newly diagnosed and recurrent brain metastases, including whole-brain radiotherapy, radiosurgery, and chemotherapy, highlighting the importance of tailoring treatments to specific patient prognostic subgroups.

Emerging therapies, such as new radiosensitizers and cytotoxic agents, are being explored to improve local control and survival rates while managing the risk of late neurotoxicity associated with these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and chemotherapy of brain metastases. Soffietti, R., Costanza, A., Laguzzi, E., et al.[2018]

Stereotactic radiosurgery is a commonly used and effective treatment for recurrent or progressive brain metastases, showing good results in local brain control and patient survival based on various clinical studies.

This treatment is considered relatively safe, with a low incidence of brain toxicity side effects, but further well-designed randomized studies are needed to refine patient selection and treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage stereotactic radiosurgery for brain metastases. Klironomos, G., Bernstein, M.[2013]

Salvage stereotactic radiotherapy (SRT) using CyberKnife for recurrent gliomas showed an acceptable safety profile, with only 11.4% of patients experiencing significant toxicity, specifically radiation-induced brain necrosis.

The treatment resulted in a median overall survival of 9 months and a progression-free survival of 3 months, indicating that SRT can be a viable option for patients with recurrent gliomas after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. Adachi, K., Hayashi, K., Kagawa, N., et al.[2019]

Radiation oncologists are exploring various innovative approaches, such as interstitial implants and stereotactic radiosurgery, to enhance cure rates for primary brain tumors while aiming to reduce long-term side effects.

These new radiation techniques must be integrated into a comprehensive treatment plan that includes other therapies to effectively manage primary malignant brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving radiotherapy for brain tumors. Woo, SY., Maor, MH.[2005]

Reirradiation for patients with brain metastases can effectively alleviate symptoms and improve survival rates, with minimal late neurotoxicity, making it a valuable treatment option that is often underutilized.

Recent studies indicate that stereotactic radiosurgery, in addition to traditional whole brain radiotherapy, offers promising results for reirradiation, enhancing treatment options for patients with recurrent brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reirradiation for progressive brain metastases. Bahl, A., Kumar, M., Sharma, DN., et al.[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]

The phase II trial aims to evaluate the safety and feasibility of combining regional hyperthermia with moderately dose-escalated salvage radiotherapy for recurrent prostate cancer, focusing on minimizing severe adverse events.

If proven safe and feasible, this study could lead to a larger phase III trial to determine if adding hyperthermia improves treatment outcomes, specifically biochemical control of the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial. Müller, AC., Zips, D., Heinrich, V., et al.[2021]

Salvage reirradiation (re-RT) using external beam radiation therapy (EBRT), especially stereotactic radiation therapy (SBRT), shows promising outcomes for treating local failure in prostate cancer, with a local control rate of 83.2% and biochemical relapse-free survival of 59.3% based on a review of 19 studies involving 428 patients.

The treatment demonstrated low rates of severe toxicity, with only 3.4% of patients experiencing grade 3 or higher genitourinary toxicity and 2.0% gastrointestinal toxicity, suggesting that re-RT is a relatively safe option, particularly when partial prostate re-RT is used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis. Corkum, MT., Mendez, LC., Chin, J., et al.[2022]

Despite aggressive treatments for brain tumors, recurrence remains common, and there is currently no standard care for managing recurrent tumors, making treatment challenging.

Advancements in radiation therapy techniques, such as IMRT and SRS, have improved tumor targeting and reduced damage to healthy brain tissue, but the benefits and risks of reirradiation for recurrent tumors are still debated, particularly regarding survival and toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of reirradiation in the management of recurrent brain tumors. De Pietro, R., Zaccaro, L., Marampon, F., et al.[2023]

In a study of 33 patients with recurrent brain metastases treated with salvage stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), local progression occurred in only 9.8% of brain metastases, indicating effective local control.

After 2 years, 37.7% of patients were alive, and 72% were free from distant brain failure, with no increase in toxicity or neurologically related deaths, suggesting that focal radiotherapy is a safe and effective option for managing limited brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated stereotactic radiosurgery for recurrent brain metastases: An effective strategy to control intracranial oligometastatic disease. Jablonska, PA., Serrano Tejero, D., Calvo González, A., et al.[2020]

CyberKnife stereotactic radiotherapy (SRT) was found to be an effective treatment for recurrent glial tumors, with a median survival time of 22.3 months after recurrence among 37 patients studied over a follow-up period of up to 57 months.

The treatment showed no significant toxicity, indicating that SRT is a safe option, especially for high-grade tumors, which had a median survival of 29 months compared to 19 months for low-grade tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of stereotactic radiotherapy as salvage treatment for recurrent malignant gliomas. Ekici, K., Ozseker, N., Mayadagli, A., et al.[2018]

Re-irradiation with salvage radiation therapy (SRT) for relapsing glioblastoma multiforme (GBM) showed a median survival of 19.2 months, indicating it is a valid treatment option for these patients.

Patients receiving lower daily radiation doses (1.6 to 1.65 Gy) and a total dose greater than 40 Gy had significantly better survival outcomes (24.6 months), suggesting that treatment schedules should be optimized to enhance efficacy while minimizing damage to surrounding brain tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage Radiation Therapy for Patients With Relapsing Glioblastoma Multiforme and the Role of Slow Fractionation. Ciernik, IF., Gager, Y., Renner, C., et al.[2022]

References

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

Radiotherapy and chemotherapy of brain metastases. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Salvage stereotactic radiosurgery for brain metastases. [2013]

3. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. [2019]

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

Improving radiotherapy for brain tumors. [2005]

5. India pubmed.ncbi.nlm.nih.gov

Reirradiation for progressive brain metastases. [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. England pubmed.ncbi.nlm.nih.gov

Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial. [2021]

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

A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis. [2022]

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

The evolving role of reirradiation in the management of recurrent brain tumors. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Repeated stereotactic radiosurgery for recurrent brain metastases: An effective strategy to control intracranial oligometastatic disease. [2020]

12. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of stereotactic radiotherapy as salvage treatment for recurrent malignant gliomas. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Salvage Radiation Therapy for Patients With Relapsing Glioblastoma Multiforme and the Role of Slow Fractionation. [2022]