Dabrafenib + Trametinib After Radiation for Brain Cancer
Recruiting in Palo Alto (17 mi)
+137 other locations
Overseen ByRishi R Lulla
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 6 jurisdictions
Trial Summary
What is the purpose of this trial?This trial studies how well dabrafenib and trametinib work after radiation therapy in children and young adults with a specific type of brain tumor. These drugs help stop tumor growth by blocking signals that tell the cells to multiply. Dabrafenib has been developed and tested extensively for a specific type of skin cancer, showing effectiveness both alone and when used with trametinib.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you have a seizure disorder, you can participate if your seizures are well controlled with non-enzyme inducing anticonvulsants. It's best to discuss your specific medications with the trial team.
What data supports the idea that Dabrafenib + Trametinib After Radiation for Brain Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of Dabrafenib + Trametinib after radiation for brain cancer. The studies focus on different radiotherapy techniques and their advancements, but they do not directly address the combination of Dabrafenib and Trametinib with radiation for brain cancer. Therefore, we cannot conclude its effectiveness based on the provided information.
12345What safety data exists for Dabrafenib + Trametinib after radiation for brain cancer?
The provided research does not directly address the safety data for Dabrafenib + Trametinib after radiation for brain cancer. However, it includes studies on the safety and toxicity of various radiotherapy techniques, such as stereotactic radiotherapy (SRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT), in different cancer treatments. These studies highlight the importance of advanced radiotherapy techniques in reducing toxicity, but specific safety data for the combination of Dabrafenib and Trametinib with radiation therapy for brain cancer is not covered in the provided abstracts.
36789Is Radiation Therapy a promising treatment for brain cancer when used with Dabrafenib and Trametinib?
Radiation Therapy, when combined with the drugs Dabrafenib and Trametinib, shows promise for treating brain cancer. This combination has been effective in treating other cancers with similar mutations, and early studies suggest it could work well for brain tumors too.
1011121314Eligibility Criteria
This trial is for children and young adults aged between 1 to 21 years with newly-diagnosed high-grade glioma that has a specific genetic change (BRAF V600 mutation). They must not have had any previous tumor-directed therapy other than surgery or corticosteroids, should be in good health otherwise, and able to follow the study procedures. Pregnant or breastfeeding females are ineligible, as well as those with certain medical conditions like uncontrolled heart disease.Inclusion Criteria
My tumor tested positive for H3 K27M mutation.
I can take care of myself but may not be able to do active work.
My spinal fluid test was negative for cancer cells.
+20 more
Exclusion Criteria
I have no allergies to dabrafenib, trametinib, or similar medications.
I do not have a tumor in my brainstem or spinal cord.
I have a history or current issue with specific eye conditions (RVO or CSR) or risk factors for them.
+13 more
Participant Groups
The trial tests how well dabrafenib combined with trametinib works after radiation therapy in patients with BRAF V600-mutant high-grade glioma. Dabrafenib targets the BRAF enzyme while trametinib targets MEK; both enzymes are involved in tumor cell growth. The goal is to see if this combination improves outcomes compared to past treatments.
1Treatment groups
Experimental Treatment
Group I: Treatment (radiation therapy, dabrafenib, trametinib)Experimental Treatment6 Interventions
Patients undergo standardized local RT 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI at baseline, on day 1 of cycles 1, 3, 5, 7, 11, 14, 17, 20, and 23 while on treatment, then at time of relapse, every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, and annually for years 4-5. Patients may also undergo lumbar puncture for CSF testing during treatment. Patients also undergo collection of blood on study.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Walter Reed National Military Medical CenterBethesda, MD
Roswell Park Cancer InstituteBuffalo, NY
Massachusetts General Hospital Cancer CenterBoston, MA
State University of New York Upstate Medical UniversitySyracuse, NY
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Early clinical outcomes for 3 radiation techniques for brain metastases: focal versus whole-brain. [2016]To present our novel technique for brain metastases (low-dose whole brain radiation therapy [WBRT] with simultaneous integrated boost (SIB) and focal, frameless stereotactic intensity modulated radiotherapy [IMRT]) in the context of patterns of failure, dosimetry, acute toxicity, and overall survival for 3 different radiation techniques.
Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in the skull base. [2022]This study evaluates a possible advantage of intensity-modulated stereotactic radiotherapy (IMSRT) over stereotactic conformal radiotherapy (SCRT) in the treatment of lesions in the base of the skull.
Comparison of 3D confromal radiotherapy and intensity modulated radiotherapy with or without simultaneous integrated boost during concurrent chemoradiation for locally advanced head and neck cancers. [2021]Radiotherapy techniques have evolved from 3D conformal radiotherapy (3D-CRT) to intensity modulated radiotherapy (IMRT) where boost fields are delivered either sequentially (IMRTseq) or with a simultaneous integrated boost (IMRT+SIB). Our goal was to compare the outcomes of patients treated with IMRT+SIB to traditional standards.
Improving radiotherapy for brain tumors. [2005]Radiation oncologists treating patients with primary brain tumors are faced with two important issues: How to improve the cure rate over that which is achievable with the current radiotherapy modalities and how to decrease long-term morbidity while maintaining or improving the cure rate. Several new approaches are being studied, including interstitial implants, stereotactic radiosurgery, new radiation modalities, radiosensitizers, hyperthermia, and altered fractionation programs. It is nonetheless important to remember that such innovative radiotherapy must be incorporated into the overall multimodal therapy for patients with primary malignant brain tumors.
Radiotherapy for brain tumors. [2019]Over the last 2 years, several advances have been made in the field of radiotherapy for brain tumors. Key advances are summarized in this review. Crucial technologic advances, such as radiosurgery, fractionated stereotactic radiotherapy, and intensity-modulated radiotherapy, are discussed. Better understanding of the interaction between the processes of angiogenesis, apoptosis, cell-cycle regulation, and signal transduction and the effects of ionizing radiation has made it clear that many of these "new agents" are, in fact, valuable modulators of the radiation response. Another exciting molecular discovery is the recognition of radiation-induced promoters that can be exploited to cause spatially and temporally configured expression of selected genes; this approach may represent the ideal application of conformal radiation techniques in the future, yielding well-defined genetic changes in specifically targeted tissues. The final "frontier" covered in this review is the newer categories of radiosensitizers, ranging from topoisomerase-I inhibitors, to expanded metalloporphyrins, to oxygen- dissociating agents.
Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases. [2021]Stereotactic radiotherapy (SRT) is the standard treatment for brain metastases of non-small-cell lung cancer (NSCLC) and melanoma, mostly in combination with immunotherapy. The objective was to retrospectively evaluate the influence of the time-lapse between immunotherapy and stereotactic radiotherapy on toxicity.
Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8-5.4, p
Radiotherapy of Cervical Cancer. [2017]Curative-intent radical radiotherapy of cervical cancer consists of external-beam radiotherapy, brachytherapy, and concomitant chemotherapy with cisplatin. For each element, new developments aim to improve tumor control rates or treatment tolerance. Intensity-modulated radiotherapy (IMRT) has been shown to reduce gastrointestinal toxicity and can be used to selectively increase the radiotherapy dose. Individualized, image-guided brachytherapy enables better adaptation of high-dose volumes to the tumor extension. Intensification of concomitant or sequential systemic therapy is under evaluation.
Current use of stereotactic body radiation therapy for low and intermediate risk prostate cancer: A National Cancer Database Analysis. [2021]Recent studies have demonstrated both safety and efficacy of stereotactic body radiation therapy (SBRT) as monotherapy in the treatment of low and intermediate risk prostate cancer. Our study aims to provide an update analyzing the use of SBRT compared with conventional and hypofractionated regimens in the United States from 2004 to 2015.
Phase I study of trametinib in combination with whole brain radiation therapy for brain metastases. [2023]Trametinib is a MEK inhibitor with intracranial activity indicated for BRAF-mutant metastatic malignancies. Yet, the safety of trametinib concurrent with whole brain radiation therapy (WBRT) is unknown. We performed a single-institution, prospective, 3 + 3, phase I clinical trial to determine the maximum tolerated dose (MTD) of trametinib with WBRT.
Cerebral infarction after treatment with dabrafenib plus trametinib for BRAF-V600E-positive non-small cell lung cancer: A case report. [2023]Dabrafenib plus trametinib is the standard treatment for BRAF V600E-mutated non-small cell lung cancer. No treatment-related cerebral infarction (CI) has been reported in previous clinical trials. Here, we described a 61-year-old Japanese man with BRAF V600E-mutated lung adenocarcinoma treated with dabrafenib plus trametinib as a third-line treatment. On the 10th day of dabrafenib plus trametinib treatment, the patient developed fever and was urgently hospitalized on the 18th day owing to impaired consciousness. The patient had disseminated intravascular coagulation because of infection, was treated with thrombomodulin and ceftriaxone, and subsequently improved. On the 44th day, dabrafenib plus trametinib was resumed with a one-step dose reduction. Three hours after the first oral administration, the patient developed chills, fever, and hypotension. He received intravenous fluids. On the 64th day, 20 mg prednisolone was administered from the previous day, and dabrafenib plus trametinib was resumed with a further one-step reduction in dose. Five hours after the first oral administration, the patient developed fever, hypotension, paralysis of the right upper and lower limbs, and dysarthria appeared. Head magnetic resonance imaging revealed multiple cerebral infarcts. Hemoconcentration because of intravascular dehydration may have caused CI. In conclusion, CI should be taken into consideration during treatment with dabrafenib plus trametinib.
Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity. [2023]BRAF V600E is a common oncogenic driver in a variety of primary brain tumors. Dual inhibitor therapy using dabrafenib (a selective oral inhibitor of several mutated forms of BRAF kinase) and trametinib (a reversible inhibitor of MEK1 and MEK2) has been used successfully for treatment of metastatic melanoma, anaplastic thyroid cancer, and other tumor types, but has been reported in only a few patients with primary brain tumors and none with pleomorphic xanthoastrocytoma. Here, the authors report on the substantial clinical response and reduction in cutaneous toxicity in a case series of BRAF V600E primary brain cancers treated with dual BRAF/MEK inhibitor therapy.
Treatment related toxicities with combination BRAF and MEK inhibitor therapy in resected stage III melanoma. [2022]Combination dabrafenib (D) and trametinib (T) is an FDA approved adjuvant therapy for patients with resected stage III BRAF-mutant melanoma. We describe treatment-related toxicities with adjuvant D+T in a real-world population through a retrospective case series. The primary endpoint was development of toxicities.
Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. [2022]Combined therapy with dabrafenib plus trametinib was approved in several countries for treatment of BRAF V600E-mutant anaplastic thyroid cancer (ATC) based on an earlier interim analysis of 23 response-assessable patients in the ATC cohort of the phase II Rare Oncology Agnostic Research (ROAR) basket study. We report an updated analysis describing the efficacy and safety of dabrafenib plus trametinib in the full ROAR ATC cohort of 36 patients with ∼4 years of additional study follow-up.