Genomically-Guided Treatment Trial in Brain Metastases
概览
- 阶段
- 2 期
- 干预措施
- Abemaciclib
- 疾病 / 适应症
- CDK Gene Mutation
- 发起方
- Alliance for Clinical Trials in Oncology
- 入组人数
- 50
- 试验地点
- 831
- 主要终点
- Objective response rate in the brain
- 状态
- 进行中（未招募）
- 最后更新
- 19天前
概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES: I. To determine the activity of a CDK inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations associated with sensitivity to CDK inhibitors as measured by response rate (Response Assessment in Neuro-Oncology \[RANO\] criteria). II. To determine the activity of a PI3K inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations in the PI3K pathway as measured by response rate (RANO criteria). III: To determine the activity of an NTRK/ROS1 inhibitor in patients with progressive brain metastases derived from lung cancer harboring actionable NTRK/ROS1 gene fusions as measured by response rate (RANO criteria). IV. To determine the activity of an KRAS G12C inhibitor in patients with progressive brain metastases derived from lung cancer, and other cancers harboring a KRAS G12C mutation as measured by response rate (RANO criteria). SECONDARY OBJECTIVES: I. To evaluate the systemic response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in each of the cohorts determined by treatment and primary cancer type. II. To evaluate the clinical benefit rate (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]) by Brain Metastases (BM)-RANO for central nervous system (CNS) in each of the cohorts determined by treatment and primary cancer type. III. To evaluate the clinical benefit rate (CR + PR + SD) by RECIST for extracranial disease in each of the cohorts determined by treatment and primary cancer type. IV. To evaluate the duration of response by BM-RANO in each of the cohorts determined by treatment and primary cancer type. V. To evaluate the duration of response by RECIST in each of the cohorts determined by treatment and primary cancer type. VI. To evaluate the progression-free survival for intracranial disease in each of the cohorts determined by treatment and primary cancer type. VII. To evaluate the progression-free survival for extracranial disease in each of the cohorts determined by treatment and primary cancer type. VIII. To evaluate the site of first progression (CNS versus \[vs\] non-CNS) in each of the cohorts determined by treatment and primary cancer type. IX. To evaluate the overall survival in each of the cohorts determined by treatment and primary cancer type. X. To evaluate the toxicity profile of agents in patients with brain metastases in each of the cohorts determined by treatment and primary cancer type. OUTLINE: Patients are assigned to 1 of 4 arms. ARM I (CDK GENE MUTATION): Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II (PI3K GENE MUTATION): Patients receive PI3K inhibitor paxalisib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM III (NTRK/ROS1 GENE MUTATION): Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM IV (KRAS G12C MUTATION): Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 8 weeks for 2 years, then every 3 months for years 3-4, and then every 6 months thereafter for up to 5 years after registration.
研究者
入排标准
入选标准
- •PRE-REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS) • Tissue available for biomarker testing (any brain metastasis tissue and extracranial site from any prior resection or biopsy).
- •REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS)
- •Participants must have histologically confirmed parenchymal metastatic disease to the brain from any solid tumor. Note: this includes patients that have controlled extracranial disease with progressive intracranial metastasis, as well as patients that have progressive intracranial and extracranial disease.
- •New or progressive brain metastases are defined as any one of the following:
- •Untreated measurable lesions in patients who have received surgery and/or stereotactic radiosurgery (SRS) to one or more other lesions.
- •Progressive measurable lesions after radiation, surgery, or prior systemic therapy
- •Residual or progressive lesions after surgery if asymptomatic.
- •Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS and then whose lesions have progressed by BM-RANO criteria or there are new lesions, are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression. For patients with NTRK or ROS1 mutations, entrectinib may be used for newly diagnosed brain metastases. Similarly, for patients with KRAS G12C mutations, MRTX849 may be used for newly diagnosed brain metastases.
- •Patients who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible, but such patients must be asymptomatic or neurologically stable from their CNS metastases.
- •Measurable CNS disease (=\> 10 mm).
排除标准
- 未提供
研究组 & 干预措施
Arm I (CDK gene mutation)
Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Abemaciclib
Arm II (PI3K gene mutation)
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.
干预措施: PI3K Inhibitor paxalisib
Arm III (NTRK/ROS1 gene mutation)
Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Entrectinib
Arm IV (KRAS G12C mutation)
Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Adagrasib
结局指标
主要结局
Objective response rate in the brain
时间窗: Up to 5 years
Assessed per Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases. The response rate is defined as the number of patients who have achieved complete response (CR) or partial response (PR) per RANO for brain metastases criteria during treatment with CDK, PI3K, NTRK/ROS, or KRAS G12C inhibitors divided by total number of evaluable patients. The response rate and associated exact confidence interval will be estimated within each cohort defined by the targeted agent and histology.
次要结局
- Systemic response for extracranial disease(Up to 5 years)
- Clinical benefit rate for central nervous system (CNS)(Up to 5 years)
- Clinical benefit rate for extracranial disease(Up to 5 years)
- Site of first progression(Up to 24 months)
- Duration of response for brain metastases(From the time measurement criteria are met for CR or PR for brain metastases until the first date that progressive CNS disease or death is documented, assessed up to 5 years)
- Duration of response for extracranial disease(From the time measurement criteria are met for CR or PR for extracranial disease until the first date that progressive disease for extracranial disease or death is documented, assessed up to 5 years)
- Progression-free survival (PFS) - extracranial(From the first day of study treatment to the earliest date of documentation of extracranial disease progression or death from any cause, assessed up to 5 years)
- Progression-free survival (PFS) - intracranial(From first day of study treatment to the earliest date documentation of intracranial disease progression or death from any cause, assessed up to 5 years)
- Overall survival(From the first day of study treatment to death due to any cause, assessed up to 5 years)
- Incidence of adverse events(Up to 5 years)