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

Plain English Summary

Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and ALK rEarrangements is a Phase 2 clinical trial sponsored by Joshua Palmer studying Lung Cancer, NSCLC, Brain Metastases. This trial tests if delaying brain radiation is as effective as giving it upfront for lung cancer patients with brain metastases. It is for patients with a specific type of lung cancer (NSCLC) that has spread to the brain but is not causing significant symptoms. Participants will receive a targeted drug called alectinib, with some also receiving brain radiation. Alternative treatments may include other targeted therapies or different radiation approaches, depending on the patient's specific situation. The trial aims to enroll 56 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults 18 and older with a specific type of non-small cell lung cancer (NSCLC) that has spread to the brain. Patients must have brain metastases that are not causing severe symptoms and have a confirmed ALK gene rearrangement. Individuals with controlled neurological symptoms from brain metastases are eligible. Those with active infections, pregnant or breastfeeding individuals, or those with other interfering medical conditions are not eligible. This trial is studying Lung Cancer, NSCLC, Brain Metastases, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how well the treatment controls brain disease and neurological symptoms at 12 months, indicating the effectiveness of the treatment strategy in managing cancer spread to t The specific primary outcome measures are: Phase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases (12 months); Phase 1b: Safety and Feasibility (6 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for optimizing treatment for lung cancer patients with brain metastases, aiming to improve outcomes and quality of life by evaluating the best timing for brain rad Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Lung Cancer, NSCLC, Brain Metastases, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in lung cancer treatment, with a focus on a specific genetic subtype (ALK-positive), suggesting potential for a personalized medicine approach and a competi Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you, considering your specific type of lung cancer and brain metastases. Participation involves taking a daily medication (alectinib) and potentially receiving brain radiation, with regular check-ups and scans. The study lasts up to 2 years for the medication, with ongoing monitoring for treatment effects and side effects. This trial is currently recruiting participants. The trial is being conducted at 3 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 56 participants

Interventions

• DRUG: Alectinib — 600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)
• RADIATION: Stereotactic Radiosurgery — SRS dose varies by brain met size and location

Primary Outcomes

• Phase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases (12 months)
• Phase 1b: Safety and Feasibility (6 months)

Secondary Outcomes

• 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)

Full 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 8 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 review and approval of the radiation therapy plan as outlined in Section 5.
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.

Trial Locations

• Stanford University, Stanford, California, United States
• University of Colorado Cancer Center, Aurora, Colorado, United States
• Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer (NSCLC)
• Brain Metastases
• ALK-positive Lung Cancer
• Targeted Cancer Therapy
• Radiation Oncology
• Neurological Oncology
• Metastatic Cancer
• Oncology
• Cancer Treatment

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