Brain Radiotherapy for Lung Cancer
(DURABLE Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Joshua Palmer
Must be taking: Alectinib
Must not be taking: Investigational drugs
Disqualifiers: Active infection, Malabsorption, Pregnancy, others
No Placebo Group
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This study will consist of a Phase 1b and Phase 2 portion. The Phase 1b portion will enroll first followed by the Phase 2 portion. Each cycle of treatment = 28 days.
Subjects will receive alectinib twice daily. Those in the Phase 1b portion will receive alectinib alone. Those in Phase 2 Arm A will receive alectinib alone. Those in Phase 2, Arm B will receive SRS + alectinib.
A maximum of 25 cycles (2 years) of alectinib may be administered on study.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, it mentions that patients with controlled neurological symptoms using corticosteroids or anti-epileptic medications are eligible, suggesting some medications may be allowed.
What data supports the effectiveness of the treatment Alectinib and Stereotactic Radiosurgery for brain metastases in lung cancer?
Research shows that Alectinib, a drug used for lung cancer, can effectively control brain metastases (cancer spread to the brain) in patients with ALK-positive non-small-cell lung cancer, even after other treatments fail. It has been shown to improve survival outcomes when used with brain-targeted therapies.
12345Is brain radiotherapy for lung cancer generally safe in humans?
Alectinib, a drug used in treating lung cancer, is generally well tolerated but can cause serious side effects. It has shown good tolerability in studies, but patients should be aware of potential side effects like rash and hyperbilirubinemia (high levels of bilirubin in the blood).
46789How is the drug Alectinib unique in treating brain metastases from lung cancer?
Alectinib is unique because it is specifically effective for patients with ALK-positive lung cancer that has spread to the brain, even after other treatments like crizotinib have failed. It works by targeting the ALK gene rearrangements, providing a durable response for both brain and body tumors.
1251011Eligibility Criteria
This trial is for adults over 18 with Stage IV non-small cell lung cancer (NSCLC) and ALK rearrangements. They must have 1-15 brain metastases, be asymptomatic or minimally symptomatic, and not need surgery within 28 days of starting the study. Participants should speak English as their first language and agree to delay radiation therapy.Inclusion Criteria
My lung cancer is confirmed to be at stage IV.
I have 1-15 brain metastases, with only one larger than 2 cm but no larger than 3 cm.
I have brain metastases with little to no symptoms and don't need surgery soon.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase 1b Treatment
Participants receive alectinib alone, taken orally twice daily
6 months
Monthly visits for safety and feasibility assessment
Phase 2 Treatment
Participants in Arm A receive alectinib alone; Arm B receives SRS followed by alectinib
24 months
Monthly visits for treatment and monitoring
Follow-up
Participants are monitored for cognitive decline, overall survival, and disease progression
31 months
Participant Groups
The trial tests Alectinib, an oral drug taken twice daily for up to two years. Phase 1b participants receive only Alectinib; in Phase 2, one group continues with just Alectinib while another receives Stereotactic Radiosurgery (SRS) plus Alectinib.
3Treatment groups
Experimental Treatment
Group I: Phase 2: Arm BExperimental Treatment2 Interventions
Subjects will receive SRS prior to taking alectinib. 24 hours after, but no more than 7 days after last radiation dose, alectinib should be taken at 600mg orally twice daily
Group II: Phase 2: Arm AExperimental Treatment1 Intervention
600mg alectinib taken orally twice daily
Group III: Phase 1b: ExperimentalExperimental Treatment1 Intervention
600mg alectinib taken orally twice daily
Alectinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Alecensa for:
- Metastatic ALK-positive non-small cell lung cancer (NSCLC)
- Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC
🇪🇺 Approved in European Union as Alecensa for:
- Metastatic ALK-positive non-small cell lung cancer (NSCLC)
- Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford UniversityStanford, CA
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who Is Running the Clinical Trial?
Joshua PalmerLead Sponsor
Genentech, Inc.Industry Sponsor
References
Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases: A Retrospective Study. [2022]The performance of alectinib and crizotinib in untreated anaplastic lymphoma kinase (ALK)-positive patients with non-small-cell lung cancer (NSCLC) and symptomatic and synchronic brain metastases is largely unknown. This retrospective study assessed the effectiveness of alectinib and crizotinib, together with intracranial therapies in a cohort of these patients.
Real-world Use of Radiation for Newly Diagnosed Brain Metastases in Patients With ALK-positive Lung Cancer Receiving First-line ALK Inhibitor. [2022]Management paradigms now allow for systemic targeted drugs before central nervous system (CNS)-directed radiation therapy (RT) in selected asymptomatic patients with non-small cell lung cancer (NSCLC) and brain metastases (BM). We aimed to quantify how novel targeted agents with improved CNS activity, such as second-generation anaplastic lymphoma kinase (ALK) inhibitors (eg, alectinib), might affect the role of CNS-directed RT.
Alectinib-associated pneumoperitoneum in stage IV non-small cell lung cancer - A case report. [2022]Alectinib, a highly potent, highly selective, brain-penetrant anaplastic lymphoma kinase (ALK) inhibitor is now the first line therapy for patients with metastatic ALK-positive non small cell lung cancer (NSCLC).
Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC. [2019]We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease.
Control of brain metastases with alectinib in anaplastic lymphoma kinase-rearranged lung cancer. [2021]Brain metastasis from non-small cell lung cancer remains a challenge to physicians. It occurs in 30% of patients with advanced stage adenocarcinoma of lung and is often regarded as the ominous sign of disease progression and death. Alectinib is likely to be a promising agent, even after the failure of crizotinib and ceritinib, for patients with anaplastic lymphoma kinase (ALK) -driven non-small cell lung cancer with brain metastasis, resulting in a durable response for both intracranial and extra-cranial diseases.
Patient-reported outcomes in a phase II, North American study of alectinib in patients with ALK-positive, crizotinib-resistant, non-small cell lung cancer. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">In a phase II North American study (NP28761; NCT01871805), the anaplastic lymphoma kinase (ALK) inhibitor alectinib demonstrated both systemic and central nervous system (CNS) efficacy with good tolerability in patients with ALK-positive non-small cell lung cancer. We describe patient-reported outcomes (PROs) from the NP28761 study.
Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. [2022]Alectinib is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring ALK rearrangements. Although generally well tolerated, alectinib can cause serious or life-threatening side effects.
Alectinib-induced rash unresponsive to desensitization: a case report and literature review. [2023]Since the inception of targeted therapies in treating lung cancer, providers have had to be aware of a new host of side effects when selecting management options for patients. Although targeted therapies are creating increased hope for patients with non-small cell lung cancers (NSCLC), understanding their side effects presents a challenge for providers. Alectinib, a second-generation tyrosine kinase inhibitor, is a targeted therapy used in patients with non-small cell lung cancer found to have anaplastic lymphoma kinase (ALK) mutations. Alectinib is the focus of this case report and literature review as we seek to understand side effects providers may encounter when prescribing these therapies.
Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. [2022]Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib.
Profile of alectinib for the treatment of ALK-positive non-small cell lung cancer (NSCLC): patient selection and perspectives. [2020]Discovered in 2007, anaplastic lymphoma kinase (ALK) gene rearrangements positive (ALK+) lung cancers compose a small subset of non-small cell lung cancer (NSCLC), with rapidly expanded treatments. There are currently several ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib which have been licensed by the US Food and Drug Administration or the European Medicines Agency for the treatment of ALK+ NSCLC patients. Along with the multiple therapies, the survival of this subtype of NSCLC has been significantly expanded, even for patients whose disease has spread in the brain. Alectinib (Alecensa), a specific ALK and rearranged during transfection tyrosine kinase inhibitor is approved as first-line therapy for metastatic ALK+ NSCLC patients. It is additionally approved for ALK+ NSCLC previously treated with crizotinib. The main aim of this review is to assemble on the efficacy of alectinib for the treatment of ALK+ NSCLC, to elaborate the activity of the drug in the central nervous system, and to debate on which is the position of this compound in the treatment course of ALK+ lung cancer patients.
Marked improvement in leptomeningeal carcinomatosis and spinal cord metastases following alectinib treatment of crizotinib-resistant, ALK-positive lung adenocarcinoma. [2020]We report a case of 50-year-old Japanese female with anaplastic lymphoma kinase (ALK)-positive, crizotinib-resistant lung adenocarcinoma, whose leptomeningeal carcinomatosis and spinal cord metastases were dramatically improved by the second-generation ALK inhibitor alectinib. Magnetic resonance imaging (MRI) revealed multiple brain metastases at diagnosis of lung cancer. Carboplatin/paclitaxel/bevacizumab chemotherapy was administered, but enlargement of brain tumors was observed after 3 months. Gamma knife radiosurgery was performed and then the patient received second-line chemotherapy with crizotinib. After 4 months brain MRI revealed the development of leptomeningeal carcinomatosis. Despite the patient undergoing whole brain radiotherapy, spinal cord metastases appeared. Third-line chemotherapy with alectinib was initiated for the management of metastases in central nervous system (CNS) including those in the leptomeninges and spine cord. After 3 months, marked tumor responses were observed in both the leptomeningeal carcinomatosis and spinal cord metastases. This report suggests that alectinib is a promising drug for ALK-positive lung adenocarcinoma with CNS metastases.