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

Primary Purpose

Lung Cancer, NSCLC, Brain Metastases

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Alectinib
Stereotactic Radiosurgery
Sponsored by
Joshua Palmer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

General Inclusion Criteria: Subject must meet all of the following applicable inclusion criteria to participate in this study: 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. First language must be English. 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 6 weeks prior to radiation. Prior non-ALK directed therapy for metastatic disease is permitted. Patients who have received prior neoadjuvant, 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 agreement to delay radiation therapy. 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. 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. 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: 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. History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer. Acute viral, autoimmune, alcoholic, or other types of acute hepatitis.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Phase 1b: Experimental

    Phase 2: Arm A

    Phase 2: Arm B

    Arm Description

    600mg alectinib taken orally twice daily

    600mg alectinib taken orally twice daily

    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

    Outcomes

    Primary Outcome Measures

    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.
    Phase 1b: Safety and Feasibility
    Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities.

    Secondary Outcome Measures

    Intracranial progression-free survival at 12 months (icPFS12)
    icPFS12 is the percentage of patients with icPD at 12 months defined by RANO-BM from randomization or death.
    Intracranial disease control rate (icDCR)
    icDCR defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), per RANO-BM.
    Intracranial response rate (icRR)
    icRR defined as the percentage of patients with a complete response (CR) and partial response (PR), per RANO-BM.
    Intracranial duration of response (icDOR)
    icDOR defined as the time when the criteria for CR or PR per RANO-BM were first met to the occurrence of an icPFS event
    Extracranial PFS
    Extracranial PFS will be defined as time from randomization to progression per RECIST v1.1
    Assess Overall survival (OS)
    OS defined as the time from randomization to death from any cause.
    Safety and Tolerability
    Safety and tolerability will be assessed by measuring the frequency and severity of adverse events based on CTCAE v5.0
    Cognitive decline at 12 and 24 months
    Rate of cognitive decline, defined as 1 standard deviation decline from baseline cognitive function in at least 1 cognitive test.
    Symptomatic radiation necrosis at 12 and 24 months
    Incidence of symptomatic radiation necrosis, defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery.

    Full Information

    First Posted
    July 26, 2023
    Last Updated
    October 16, 2023
    Sponsor
    Joshua Palmer
    Collaborators
    Genentech, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05987644
    Brief Title
    Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and ALK rEarrangements
    Acronym
    DURABLE
    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

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    February 2024 (Anticipated)
    Study Completion Date
    February 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Joshua Palmer
    Collaborators
    Genentech, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Lung Cancer, NSCLC, Brain Metastases

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    56 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Phase 1b: Experimental
    Arm Type
    Experimental
    Arm Description
    600mg alectinib taken orally twice daily
    Arm Title
    Phase 2: Arm A
    Arm Type
    Experimental
    Arm Description
    600mg alectinib taken orally twice daily
    Arm Title
    Phase 2: Arm B
    Arm Type
    Experimental
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Alectinib
    Intervention Description
    600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)
    Intervention Type
    Radiation
    Intervention Name(s)
    Stereotactic Radiosurgery
    Other Intervention Name(s)
    SRS
    Intervention Description
    SRS dose varies by brain met size and location
    Primary Outcome Measure Information:
    Title
    Phase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases
    Description
    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.
    Time Frame
    12 months
    Title
    Phase 1b: Safety and Feasibility
    Description
    Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities.
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Intracranial progression-free survival at 12 months (icPFS12)
    Description
    icPFS12 is the percentage of patients with icPD at 12 months defined by RANO-BM from randomization or death.
    Time Frame
    12 months
    Title
    Intracranial disease control rate (icDCR)
    Description
    icDCR defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), per RANO-BM.
    Time Frame
    31 months
    Title
    Intracranial response rate (icRR)
    Description
    icRR defined as the percentage of patients with a complete response (CR) and partial response (PR), per RANO-BM.
    Time Frame
    31 months
    Title
    Intracranial duration of response (icDOR)
    Description
    icDOR defined as the time when the criteria for CR or PR per RANO-BM were first met to the occurrence of an icPFS event
    Time Frame
    31 months
    Title
    Extracranial PFS
    Description
    Extracranial PFS will be defined as time from randomization to progression per RECIST v1.1
    Time Frame
    31 months
    Title
    Assess Overall survival (OS)
    Description
    OS defined as the time from randomization to death from any cause.
    Time Frame
    31 months
    Title
    Safety and Tolerability
    Description
    Safety and tolerability will be assessed by measuring the frequency and severity of adverse events based on CTCAE v5.0
    Time Frame
    6 months
    Title
    Cognitive decline at 12 and 24 months
    Description
    Rate of cognitive decline, defined as 1 standard deviation decline from baseline cognitive function in at least 1 cognitive test.
    Time Frame
    12, 24 months
    Title
    Symptomatic radiation necrosis at 12 and 24 months
    Description
    Incidence of symptomatic radiation necrosis, defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery.
    Time Frame
    12, 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    General Inclusion Criteria: Subject must meet all of the following applicable inclusion criteria to participate in this study: 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. First language must be English. 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 6 weeks prior to radiation. Prior non-ALK directed therapy for metastatic disease is permitted. Patients who have received prior neoadjuvant, 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 agreement to delay radiation therapy. 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. 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. 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: 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. History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer. Acute viral, autoimmune, alcoholic, or other types of acute hepatitis.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Joshua D Palmer, MD
    Phone
    614-293-0871
    Email
    joshua.palmer@osumc.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Kimberly Cameron
    Phone
    317-634-5842
    Ext
    39
    Email
    kcameron@hoosiercancer.org
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Joshua D Palmer, MD
    Organizational Affiliation
    The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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