Brief Summary

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

25mo left

Started Oct 2019

Longer than P75 for phase_2

Geographic Reach

1 country

435 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

8.6 years study duration

Study Progress76%

Oct 2019Jun 2028

First Submitted

Initial submission to the registry

June 14, 2019

Completed

7 days until next milestone

First Posted

Study publicly available on registry

June 21, 2019

Completed

4 months until next milestone

Study Start

First participant enrolled

October 17, 2019

Completed

7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2026

Expected

1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2028

Last Updated

April 13, 2026

Status Verified

April 1, 2026

Enrollment Period

7 years

First QC Date

June 14, 2019

Last Update Submit

April 9, 2026

Conditions

CDK Gene Mutation ROS1 Gene Mutation Metastatic Malignant Solid Neoplasm NTRK Family Gene Mutation PI3K Gene Mutation KRAS G12C Mutation Metastatic Malignant Neoplasm in the Brain

Outcome Measures

Primary Outcomes (1)

Objective response rate in the brain
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.
Up to 5 years

Secondary Outcomes (10)

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
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
+5 more secondary outcomes

Study Arms (4)

Arm I (CDK gene mutation)

EXPERIMENTAL

Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Abemaciclib

Arm II (PI3K gene mutation)

EXPERIMENTAL

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.

Drug: PI3K Inhibitor paxalisib

Arm III (NTRK/ROS1 gene mutation)

EXPERIMENTAL

Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Entrectinib

Arm IV (KRAS G12C mutation)

EXPERIMENTAL

Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Adagrasib

Interventions

AbemaciclibDRUG

Given PO

Arm I (CDK gene mutation)

EntrectinibDRUG

Given PO

Arm III (NTRK/ROS1 gene mutation)

AdagrasibDRUG

Given PO

Also known as: MRTX849

Arm IV (KRAS G12C mutation)

PI3K Inhibitor paxalisibDRUG

Given PO

Arm II (PI3K gene mutation)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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).
Ability to obtain magnetic resonance imaging (MRI)s with contrast
No surgery within 2 weeks prior to or after registration.
No chemotherapy within 14 days prior to registration (Note: for abemaciclib arm, a 21-day chemotherapy washout is required).
For melanoma, patients must have progressed after prior immune checkpoint blockade or for BRAF positive melanoma, BRAF/MEK inhibitors.
For lung cancer, EGFR mutant patients must have failed EGFR therapies
+46 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Mirati Therapeutics Inc.collaborator
Genentech, Inc.collaborator
Eli Lilly and Companycollaborator
National Cancer Institute (NCI)collaborator
Kazia Therapeutics Limitedcollaborator
Alliance for Clinical Trials in Oncologylead

Study Sites (435)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC