Clinical trial NCT05987644: Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and ALK rEarrangements
Official title: DURABLE: Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and rEarrangements
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
NSCLC
Brain Metastases
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2023-08-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: General Inclusion Criteria:

Subject must meet all of the following applicable inclusion criteria to participate in this study:

1. 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.
2. Age ≥ 18 years at the time of consent.
3. Fluent English skills with comprehensive/speaking skills equal to those of a native English speaker as assessed by the site investigator.
4. ECOG Performance Status of ≤ 2 within 14 days prior to registration.
5. Histological or cytological confirmation of Stage IV (per AJCC 8th edition) non-small cell lung cancer (NSCLC).
6. At least one intracranial metastasis on MRI imaging.
7. Confirmation of positive ALK rearrangement per local standard of care testing.
8. 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.
9. Subjects must be planning on therapy with alectinib. Alectinib may have been started up to 6 weeks prior to registration.
10. 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.
11. Documentation of consultation with a radiation oncologist confirming agreement to delay radiation therapy.
12. Demonstrate adequate organ function as defined in the protocol. All screening labs to be obtained within 14 days prior to registration.
13. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. See protocol for definition of childbearing potential.
14. 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.
15. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
16. Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
17. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

Subjects meeting any of the criteria below may not participate in the study:

1. Active infection requiring systemic therapy.
2. Malabsorption syndrome or other condition that would interfere with enteral absorption
3. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
4. 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.
5. Treatment with any investigational drug within 28 days prior to registration.
6. Acute viral, autoimmune, alcoholic, or other types of acute hepatitis.

Primary outcomes:
measure: Phase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases
timeFrame: 12 months
measure: Phase 1b: Safety and Feasibility
timeFrame: 6 months
Secondary outcomes:
measure: Intracranial progression-free survival at 12 months (icPFS12)
timeFrame: 12 months
measure: Intracranial disease control rate (icDCR)
timeFrame: 31 months
measure: Intracranial response rate (icRR)
timeFrame: 31 months
measure: Intracranial duration of response (icDOR)
timeFrame: 31 months
measure: Extracranial PFS
timeFrame: 31 months
measure: Assess Overall survival (OS)
timeFrame: 31 months
measure: Safety and Tolerability
timeFrame: 6 months
measure: Cognitive decline at 12 and 24 months
timeFrame: 12, 24 months
measure: Symptomatic radiation necrosis at 12 and 24 months
timeFrame: 12, 24 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: The Ohio State University Comprehensive Cancer Center
name: Joshua D Palmer, MD
role: PRINCIPAL_INVESTIGATOR
References: