Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and ALK rEarrangements

NCT05987644 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCRN-LUN21-534
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

NSCLC; Lung Cancer; Brain Metastases

Outcome Measures

Primary Outcomes (2)

• Phase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases

  Neurological status will be measured by a composite endpoint of: -Inntracranial progression(icPD) by RANO-BM criteria or death during the first 12 months. OR -Symptomatic radiation necrosis during the first 12 months. Symptomatic radiation necrosis is defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery. OR -Cognitive decline, defined as 1 standard deviation decline from baseline cognitive function during the first 12 months.

  12 months

• Phase 1b: Safety and Feasibility

  Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities.

  6 months

Secondary Outcomes (9)

• Intracranial progression-free survival at 12 months (icPFS12)

  12 months

• Intracranial disease control rate (icDCR)

  31 months

• Intracranial response rate (icRR)

  31 months

• Intracranial duration of response (icDOR)

  31 months

• Extracranial PFS

  31 months

Study Arms (3)

Phase 1b: Experimental

EXPERIMENTAL

600mg alectinib taken orally twice daily

Drug: Alectinib

Phase 2: Arm A

EXPERIMENTAL

600mg alectinib taken orally twice daily

Drug: Alectinib

Phase 2: Arm B

EXPERIMENTAL

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

Drug: Alectinib; Radiation: Stereotactic Radiosurgery

Interventions

Alectinib DRUG

600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)

Phase 1b: Experimental; Phase 2: Arm A; Phase 2: Arm B

Stereotactic Radiosurgery RADIATION

SRS dose varies by brain met size and location

Also known as: SRS

Phase 2: Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Fluent English skills with comprehensive/speaking skills equal to those of a native English speaker as assessed by the site investigator.
• ECOG Performance Status of ≤ 2 within 14 days prior to registration.
• Histological or cytological confirmation of Stage IV (per AJCC 8th edition) non-small cell lung cancer (NSCLC).
• At least one intracranial metastasis on MRI imaging.
• Confirmation of positive ALK rearrangement per local standard of care testing.
• All subjects must have brain metastases and be either asymptomatic or minimally symptomatic per investigator discretion without plan for surgical intervention within 28 days of study start. Patients with neurological symptoms that are controlled with dose of corticosteroids or anti-epileptic medications are eligible. Patients with asymptomatic leptomeningeal disease may be eligible for trial providing they meet all other eligibility criteria.
• Subjects must be planning on therapy with alectinib. Alectinib may have been started up to 8 weeks prior to registration.
• Prior non-ALK directed therapy for metastatic disease is permitted. Patients who have received prior neoadjuvant or adjuvant chemotherapy, radiotherapy, immunotherapy (PD-1 or PD-L1 monoclonal antibodies) or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 3 months from registration since the last chemotherapy, radiotherapy, immunotherapy, or chemoradiotherapy cycle.
• Documentation of consultation with a radiation oncologist confirming review and approval of the radiation therapy plan as outlined in Section 5.
• Demonstrate adequate organ function as defined in the protocol. All screening labs to be obtained within 14 days prior to registration.
• Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. See protocol for definition of childbearing potential.
• Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception as outlined in the protocol.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Active infection requiring systemic therapy.
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
• Treatment with any investigational drug within 28 days prior to registration.
• Acute viral, autoimmune, alcoholic, or other types of acute hepatitis.

Sponsors & Collaborators

• Joshua Palmer: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Stanford University

Stanford, California, 94305, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Brain Neoplasms

Interventions

alectinib; Radiosurgery

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Joshua D Palmer, MD

  The Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua D Palmer, MD

CONTACT

614-293-0871; joshua.palmer@osumc.edu

Amber Ryba

CONTACT

317-634-5842; aryba@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 14, 2023
• Study Start: March 7, 2024
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (3)