Targeted Therapy for Brain Cancer
Recruiting in Palo Alto (17 mi)
+299 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Alliance for Clinical Trials in Oncology
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial studies how well genetic testing works in guiding treatment for patients with solid tumors that have spread to the brain. Several genes have been found to be altered or mutated in brain metastases such as NTRK, ROS1, CDK, PI3K, or KRAS G12C. Medications that target these genes such as abemaciclib, paxalisib, entrectinib and adagrasib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Genetic testing may help doctors tailor treatment for each mutation.
How is the drug Abemaciclib, Entrectinib, and paxalisib unique for brain cancer treatment?
This drug combination is unique because it targets specific pathways involved in brain cancer, potentially offering a more precise treatment approach compared to traditional therapies. Abemaciclib and Entrectinib are known for their ability to inhibit specific proteins that help cancer cells grow, while paxalisib targets the PI3K/mTOR pathway, which is often active in brain tumors.
12347What data supports the effectiveness of the drug Abemaciclib, Verzenio, LY2835219, Ramiven, Abemaciclib, Entrectinib, Rozlytrek, paxalisib, paxalisib, GDC-0084 for brain cancer?
Research on similar drugs, like osimertinib and ceritinib, shows they can effectively reach the brain and treat tumors there, suggesting that targeted therapies can be promising for brain cancer.
24567Will I have to stop taking my current medications?
The trial requires a washout period for certain medications. You must stop chemotherapy at least 14 days before joining the study, and for the abemaciclib arm, a 21-day washout is needed. If you're on strong CYP3A4 inhibitors or inducers, you must stop them 14 days before starting the trial. For the entrectinib arm, you cannot use certain stomach acid medications.
Eligibility Criteria
This trial is for patients with solid tumors that have spread to the brain, who can undergo MRI scans and haven't had recent surgery or chemotherapy. They must not be pregnant or nursing, have no uncontrolled medical issues, and not be on certain drugs affecting liver enzymes. Participants need confirmed metastatic disease in the brain from a solid tumor with specific gene alterations (NTRK, ROS1, KRAS G12C, CDK pathway or PI3K pathway) and meet other health criteria.Inclusion Criteria
I haven't had chemotherapy in the last 14 days.
I am not on any strong medication that affects liver enzyme levels.
My cancer has spread to my brain from another part of my body.
My cancer has spread to my brain recently or is getting worse.
I am not currently receiving any cancer treatments.
I am not on any strong CYP3A4 inhibitors.
I have tissue samples available from previous surgeries or biopsies for testing.
My cancer has a specific change in NTRK, ROS1, KRAS G12C, CDK, or PI3K that can be treated.
I am able to care for myself and perform daily activities.
My organs are working well and my lab tests are within normal ranges.
Exclusion Criteria
I have had a condition where my lymphocytes multiply unusually.
I have a history of cancer.
I don't have recent heart issues, uncontrolled diabetes, or high protein in my urine.
Participant Groups
The trial tests if genetic testing can guide treatment using targeted medications like abemaciclib, paxalisib, entrectinib and adagrasib for brain metastases from solid tumors. These drugs aim to block enzymes needed by tumor cells to grow by focusing on mutations found in genes related to cancer progression.
4Treatment groups
Experimental Treatment
Group I: Arm IV (KRAS G12C mutation)Experimental Treatment1 Intervention
Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II: Arm III (NTRK/ROS1 gene mutation)Experimental Treatment1 Intervention
Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group III: Arm II (PI3K gene mutation)Experimental Treatment1 Intervention
Patients receive PI3K inhibitor paxalisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group IV: Arm I (CDK gene mutation)Experimental Treatment1 Intervention
Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Abemaciclib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Verzenio for:
- Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
🇪🇺 Approved in European Union as Verzenio for:
- HR+, HER2- advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Olathe Health Cancer CenterOlathe, KS
Ascension Providence Hospitals - NoviNovi, MI
University of Michigan Health - WestWyoming, MI
Siteman Cancer Center-South CountySaint Louis, MO
More Trial Locations
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Who is running the clinical trial?
Alliance for Clinical Trials in OncologyLead Sponsor
Mirati Therapeutics Inc.Industry Sponsor
Eli Lilly and CompanyIndustry Sponsor
Kazia Therapeutics LimitedIndustry Sponsor
National Cancer Institute (NCI)Collaborator
Genentech, Inc.Industry Sponsor
References
Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. [2021]This phase I study aimed to evaluate safety, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of voxtalisib (SAR245409, XL765), a pan-class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, in combination with temozolomide (TMZ), with or without radiation therapy (RT), in patients with high-grade glioma.
Oral Targeted Therapies and Central Nervous System (CNS) Metastases. [2022]The purpose of our review is to summarize the clinical activity of oral targeted agents against brain metastases. This includes BRAF inhibitors (dabrafenib and vemurafenib), human epidermal growth factor receptor inhibitors (lapatinib, gefitinib, erlotinib, and afatinib), multi-kinase angiogenesis inhibitors (sorafenib, sunitinib, pazopanib, and vandetanib), and ALK/c-MET (crizotinib) and ALK/IGF-1 (ceritinib) inhibitors. Effective systemic therapies are needed for long-term benefit in brain metastases and documentation of intracranial activity for many therapies is poor. Our review provides a summary of the literature with pertinent data for clinicians. This is needed as subjects with brain metastases are often prevented from enrolling in clinical trials and investigations focused on systemic therapies for brain metastases are rare.
Phase I trial of dovitinib (TKI258) in recurrent glioblastoma. [2018]Dovitinib (TKI258) is an oral multi-tyrosine kinase inhibitor of FGFR, VEGFR, PDGFR β, and c-Kit. Since dovitinib is able to cross the blood-brain barrier and targets brain tumor-relevant pathways, we conducted a phase I trial to demonstrate its safety in recurrent glioblastoma (GBM).
A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma. [2023]Ceritinib is an orally bioavailable, small-molecule inhibitor of anaplastic lympoma kinase (ALK), insulin-like growth factor 1 receptor (IGFR1), and focal adhesion kinase (FAK), which are highly expressed in glioblastoma and many brain metastases. Preclinical and clinical studies indicate that ceritinib has antitumor activity in central nervous system (CNS) malignancies. This phase 0 trial measured the tumor pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in patients with brain metastasis or recurrent glioblastoma.
Clinical Experience using Osimertinib in Patients with Recurrent Malignant Gliomas Containing EGFR Alterations. [2023]Label="Background" NlmCategory="UNASSIGNED"> EGFR alterations are commonly observed in malignant gliomas (MG). Osimertinib, an irreversible EGFR-tyrosine kinase inhibitor, effectively penetrates the blood brain barrier and achieves therapeutic concentrations in brain tissue.
Efficacy of lazertinib for symptomatic or asymptomatic brain metastases in treatment-naive patients with advanced EGFR mutation-positive non-small cell lung cancer: Protocol of an open-label, single-arm phase II trial. [2023]Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild-type EGFR mutations. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR-TKI sensitizing and T790M-resistance mutations and has a higher brain penetration rate relative to first- and second-generation EGFR-TKIs. Therefore, osimertinib has become a preferred first-line therapy for advanced EGFR mutation-positive NSCLC. However, lazertinib, an emerging EGFR-TKI, has shown higher selectivity toward EGFR mutations and improved penetration of the blood-brain barrier compared to osimertinib in preclinical studies. This trial will evaluate the efficacy of lazertinib as a first-line therapy in patients with EGFR mutation-positive NSCLC who have brain metastases, with or without additional local therapy.
Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis. [2023]Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.