Combined Therapies for Recurrent Brain Cancer

Recruiting at 9 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat recurrent brain cancer that has spread from other parts of the body. It tests different combinations of laser therapy (Laser Interstitial Thermal Therapy) and radiation to determine which is more effective at slowing tumor growth after initial treatments fail. Suitable candidates have brain tumors that have returned despite previous radiation or surgery and have remained stable for at least three days on a specific dose of steroids (Steroid Therapy). The goal is to find more effective treatments for managing and potentially improving outcomes for patients with recurring brain tumors. As an unphased trial, this study allows patients to contribute to pioneering research that could lead to new treatment options.

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.

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

Research has shown that Laser Interstitial Thermal Therapy (LITT) is generally safe for treating brain tumors. One study found that LITT successfully removed tumors in about 85% to 95% of cases for certain types of brain tumors. Common side effects include brain swelling, temporary nerve issues, and bleeding in the head.

Radiation therapy offers another treatment option, aiming to destroy cancer cells while protecting nearby healthy tissue. It is considered effective for controlling brain tumors. Although it limits damage to normal tissue, there is a small risk of developing another type of cancer over time.

Both treatments manage brain tumors and have been used in previous patients with varying levels of success and side effects. Individual experiences may vary, so discussing these treatments with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they combine Laser Interstitial Thermal Therapy (LITT) with innovative approaches to manage recurrent brain tumors. Unlike traditional methods like surgery, chemotherapy, or standard radiation therapy, LITT uses precisely targeted laser heat to destroy tumor cells, potentially reducing damage to surrounding healthy tissue. When coupled with hypofractionated radiation therapy, it may enhance the effectiveness while minimizing side effects. This combination could offer a more precise and less invasive treatment option, giving hope for better outcomes for patients with recurrent brain cancer.

What evidence suggests that this trial's treatments could be effective for recurrent brain cancer?

Research has shown that Laser Interstitial Thermal Therapy (LITT) effectively treats recurring brain tumors. LITT uses a laser to target and destroy tumor tissue, allowing patients to continue other treatments, like immunotherapy, which can help fight cancer. This less invasive option has shown promise in managing brain tumors. In this trial, some participants will receive LITT followed by either surveillance or hypofractionated radiation therapy.

Radiation therapy, specifically intensity-modulated radiation therapy (IMRT), has also been studied for recurring brain tumors. It has proven to be a practical option for managing large tumors, helping to control their growth and extend survival. In this trial, participants may receive LITT followed by radiation therapy. Both treatments have shown potential in effectively managing brain tumors. ^{3 5 6 7 8}

Who Is on the Research Team?

Peter Fecci, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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'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.

I am mostly able to take care of myself.

Exclusion Criteria

My cancer outside the brain is quickly getting worse.

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

I cannot have surgery due to my health condition.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9122789/

Efficacy of laser interstitial thermal therapy (LITT) for newly ... Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05318612

Effectiveness of MR-guided LITT Therapy in Irresectable ... The aim of this study is to investigate the (cost-)effectiveness of LITT (Laser Interstitial Thermal Therapy) in primary irresectable glioblastoma.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0028377025000025

Synergistic effects of laser interstitial thermal therapy (LITT) ... Laser interstitial thermal therapy (LITT) has emerged as a promising minimally invasive technique for recurrent brain tumors. LITT utilizes a laser probe ...

4. thejns.org thejns.org/focus/view/journals/neurosurg-focus/57/5/article-pE4.xml

An analysis of functional outcomes following laser interstitial ... This study sought to better define the role of LITT in treating patients with recurrent HGG, examining which patients exhibit good functional outcomes after ...

5. academic.oup.com academic.oup.com/noa/article/5/1/vdad031/7091464

Efficacy of laser interstitial thermal therapy for biopsy-proven ... In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11171930/

Safety and Efficacy of Laser Interstitial Thermal Therapy as ... The pooled data suggest LITT may be a safe primary management option with tumor ablation rates of 94.8% and 84.6% in IDH-wildtype glioblastoma ...

7. hopkinsmedicine.org hopkinsmedicine.org/health/treatment-tests-and-therapies/laser-interstitial-thermal-therapy

Laser Interstitial Thermal Therapy (LiTT) Repeated LiTT treatment may be less traumatic than repeated craniotomies for recurring brain tumors. Brain Laser Ablation Side Effects and Complications.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0028377024000754

Complications following laser interstitial thermal therapy The most common complications of LITT include cerebral edema, focal neurologic deficits, and intracranial hemorrhage.