Targeted Radiation Therapy for Brain Cancer
(RAPPLE Trial)
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: British Columbia Cancer Agency
Must not be taking: Immunotherapy, Targeted therapy
Disqualifiers: Multiple sclerosis, Epilepsy, Pregnancy, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The aim of the study is to show that rapid, simple targeted radiotherapy to brain metastases with 8 Gy / 1 is non-inferior to 20 Gy / 5 in terms of overall survival for patients with poor prognosis.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on immunotherapy, targeted therapy, or hormone therapy, you cannot participate in the trial.
What data supports the effectiveness of the treatment RAPPLE for brain cancer?
Research shows that combining targeted therapies with stereotactic radiosurgery (a precise form of radiation therapy) can improve outcomes for brain metastases, which are common in brain cancer. This suggests that targeted radiation treatments like RAPPLE might be effective by leveraging similar principles.
12345Is targeted radiation therapy for brain cancer safe for humans?
Research shows that combining targeted radiation therapy with other treatments like immunotherapy can be safe, but there may be some severe side effects. Experts have developed strategies to reduce these risks, suggesting that while generally safe, careful management is needed.
678910How is the RAPid SimPLE Targeted Radiation Treatment (RAPPLE) different from other brain cancer treatments?
RAPid SimPLE Targeted Radiation Treatment (RAPPLE) is unique because it focuses on increasing the precision of radiation delivery to brain tumors, minimizing damage to surrounding healthy brain tissue, which is a common challenge with traditional radiation therapies.
1112131415Eligibility Criteria
This trial is for adults with non-blood related cancers that have spread to the brain. Participants should have multiple brain tumors that can be targeted, a life expectancy not suitable for surgery or precise radiotherapy, and some active cancer outside the brain. They must also be able to complete questionnaires, follow up with imaging tests, start treatment within two weeks of joining, and have a performance score indicating they are still somewhat active.Inclusion Criteria
My doctor thinks I won't live long enough for surgery to help.
My cancer is not related to blood cells.
All my brain tumors can be clearly identified and targeted for treatment.
+11 more
Exclusion Criteria
Pregnancy
Inability to have a brain MRI
My cancer has spread to the lining of my brain and spinal cord.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either a single treatment of 8 Gy or five treatments of 4 Gy using volumetric modulated arc therapy to brain metastases
1-5 days
1-5 visits (in-person)
Follow-up
Participants are monitored for survival, control of brain disease, adverse events, and quality of life
1 year
Participant Groups
The study is testing if one session of targeted radiation (8 Gy) is as effective as five sessions (20 Gy total) in extending overall survival for patients with poor prognosis due to brain metastases from other cancers. The goal is to determine whether this simpler and quicker treatment approach works just as well.
2Treatment groups
Experimental Treatment
Active Control
Group I: 8 Gy in 1 Fraction Volumetric Modulated Arc Therapy to Brain MetastasesExperimental Treatment1 Intervention
A single treatment of 8 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique.
Group II: 20 Gy in 5 Fractions Volumetric Modulated Arc Therapy to Brain MetastasesActive Control1 Intervention
Five treatments of 4 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique.
RAPid SimPLE Targeted Radiation Treatment is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as RAPid SimPLE Targeted Radiation Treatment for:
- Brain metastases
🇺🇸 Approved in United States as RAPid SimPLE Targeted Radiation Treatment for:
- Brain metastases
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
BC Cancer - KelownaKelowna, Canada
BC Cancer - VancouverVancouver, Canada
BC Cancer - Prince GeorgePrince George, Canada
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Who Is Running the Clinical Trial?
British Columbia Cancer AgencyLead Sponsor
Varian Medical SystemsIndustry Sponsor
References
Local recurrence patterns after postoperative stereotactic radiation surgery to resected brain metastases: A quantitative analysis to guide target delineation. [2019]In the treatment of resected metastatic brain disease, a recent phase 3 trial by the North Central Cancer Treatment Group (N107C/CEC.3) surprisingly found that the local control rate for whole-brain radiation therapy was better than that of stereotactic radiation surgery (SRS). To optimize target delineation, we performed a quantitative analysis of local failure patterns after postoperative SRS.
Improving Brain Metastases Outcomes Through Therapeutic Synergy Between Stereotactic Radiosurgery and Targeted Cancer Therapies. [2022]Brain metastases are the most common form of brain cancer. Increasing knowledge of primary tumor biology, actionable molecular targets and continued improvements in systemic and radiotherapy regimens have helped improve survival but necessitate multidisciplinary collaboration between neurosurgical, medical and radiation oncologists. In this review, we will discuss the advances of targeted therapies to date and discuss findings of studies investigating the synergy between these therapies and stereotactic radiosurgery for non-small cell lung cancer, breast cancer, melanoma, and renal cell carcinoma brain metastases.
Radiotherapy and chemotherapy of brain metastases. [2018]The authors have reviewed the results, the indications and the controversies regarding radiotherapy and chemotherapy of patients with newly diagnosed and recurrent brain metastases. Whole-brain radiotherapy, radiosurgery, hypofractionated stereotactic radiotherapy, brachytherapy and chemotherapy are the available options. New radiosensitizers and cytotoxic or cytostatic agents are being investigated. Adjuvant whole brain radiotherapy, either after surgery or radiosurgery, and prophylactic cranial irradiation in small-cell lung cancer are discussed, taking into account local control, survival, and risk of late neurotoxicity. Increasingly, the different treatments are tailored to the different prognostic subgroups, as defined by Radiation Therapy Oncology Group RPA Classes.
Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases. [2018]Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments.
Five-Fraction Stereotactic Radiotherapy for Brain Metastases-A Retrospective Analysis. [2023]To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment.
Clinical outcomes of biological effective dose-based fractionated stereotactic radiation therapy for metastatic brain tumors from non-small cell lung cancer. [2022]To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC).
Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies. [2022]Systemic, immune, and target therapies are growing in use in the management of metastatic cancers. The aim of this review was to describe up-to-date published data on the safety and tolerability of metastasis-directed hypofractionated radiation therapy (RT) when combined with newer systemic, immune, and targeted therapies and to provide suggested strategies to mitigate potential toxicities in the clinical setting.
Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium. [2023]Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.
Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: A systematic review. [2022]Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment.
Five-fraction stereotactic radiosurgery (SRS) for single inoperable high-risk non-small cell lung cancer (NSCLC) brain metastases. [2022]Achieving durable local control while limiting normal tissue toxicity with definitive radiation therapy in the management of high-risk brain metastases remains a radiobiological challenge. The objective of this study was to examine the local control and toxicity of a 5-fraction stereotactic radiosurgical approach for treatment of patients with inoperable single high-risk NSCLC brain metastases.
Targeted radiotherapy of brain tumours. [2022]The utility of external beam radiotherapy for the treatment of malignant brain tumours is compromised by the need to avoid excessive radiation damage to normal CNS tissues. This review describes the current status of targeted radiotherapy, an alternative strategy for brain tumour treatment that offers the exciting prospect of increasing the specificity of tumour cell irradiation.
Physical and biological targeting of radiotherapy. [2019]Targeting of radiotherapy can be based on improving physical dose distribution of radiation delivered or on utilization of specific biological processes for targeting. Tools for physical targeting include brachytherapy, hadron therapy, conformal radiotherapy, stereotactic radiotherapy, stereotactically guided conformal fractionated radiotherapy, and intensity-modulated radiotherapy. Biological targeting can be based on specific metabolic pathways such as uptake of iodine-131 by thyroid cancer cells, difference in substrate uptake between cancer cells and normal cells (e.g. boronophenylalanine in boron neutron capture therapy), targeting of radioactive isotopes by specific carrier molecules (radioimmunotherapy, labeled hormone derivatives or bone-seeking phosphonates), or on the distribution of elements in the body (therapy of bone metastases with a calcium analog strontium-89 or phosphorus-32).
Single-Isocenter Multitarget Stereotactic Radiosurgery Is Safe and Effective in the Treatment of Multiple Brain Metastases. [2022]Multiple studies have reported favorable outcomes for stereotactic radiosurgery (SRS) in the treatment of limited brain metastases. An obstacle of SRS in the management of numerous metastases is the longer treatment time using traditional radiosurgery. Single-isocenter multitarget (SIMT) SRS is a novel technique that permits rapid therapy delivery to multiple metastases. There is a lack of clinical evidence regarding its efficacy and safety. We report the outcomes of patients treated with this technique.
Guidelines for Multiple Brain Metastases Radiosurgery. [2019]Stereotactic radiosurgery (SRS) is an effective treatment for patients with multiple brain metastases. Three decades of increasingly powerful scientific studies have shown that SRS improves outcomes and reduces toxicity when it replaces whole-brain radiation therapy (WBRT). Expert opinion surveys of clinicians have reported that the total intracranial tumor volume rather than the number of brain metastases is related to outcomes. As a result, an increasing number of treating and referring physicians have replaced the reflex use of WBRT with SRS, unless the patient has miliary disease or carcinomatous meningitis. In the current era of immunotherapy and targeted therapies with potentially increased systemic disease survival, 10 or more tumors are routinely treated with SRS alone at most academic medical centers. In a single SRS session we routinely treat patients with cumulative tumor volumes of 25 cm3 even if they have ≥10 metastases.
Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma. [2010]Stereotactic radiotherapy (SRT) is fractionated radiotherapy delivered under stereotactic guidance to produce highly focal and precise therapy. We studied the incidence of imaging changes that can mimic tumor progression after completion of SRT for childhood low grade astrocytoma.