Brain Radiotherapy for Lung Cancer

(DURABLE Trial)

Recruiting at 1 trial location

Overseen By Amber Ryba

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Joshua Palmer

Must be taking: Alectinib

Must not be taking: Investigational drugs

Disqualifiers: Active infection, Malabsorption, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

56 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients with controlled neurological symptoms using corticosteroids or anti-epileptic medications are eligible, suggesting some medications may be allowed.

What data supports the effectiveness of the treatment Alectinib and Stereotactic Radiosurgery for brain metastases in lung cancer?

Research shows that Alectinib, a drug used for lung cancer, can effectively control brain metastases (cancer spread to the brain) in patients with ALK-positive non-small-cell lung cancer, even after other treatments fail. It has been shown to improve survival outcomes when used with brain-targeted therapies. ^{1 2 3 4 5}

Is brain radiotherapy for lung cancer generally safe in humans?

Alectinib, a drug used in treating lung cancer, is generally well tolerated but can cause serious side effects. It has shown good tolerability in studies, but patients should be aware of potential side effects like rash and hyperbilirubinemia (high levels of bilirubin in the blood). ^{4 6 7 8 9}

How is the drug Alectinib unique in treating brain metastases from lung cancer?

Alectinib is unique because it is specifically effective for patients with ALK-positive lung cancer that has spread to the brain, even after other treatments like crizotinib have failed. It works by targeting the ALK gene rearrangements, providing a durable response for both brain and body tumors. ^{1 2 5 10 11}

Research Team

Joshua D. Palmer, MD

Principal Investigator

The Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with Stage IV non-small cell lung cancer (NSCLC) and ALK rearrangements. They must have 1-15 brain metastases, be asymptomatic or minimally symptomatic, and not need surgery within 28 days of starting the study. Participants should speak English as their first language and agree to delay radiation therapy.

Inclusion Criteria

My lung cancer is confirmed to be at stage IV.

I have 1-15 brain metastases, with only one larger than 2 cm but no larger than 3 cm.

I have brain metastases with little to no symptoms and don't need surgery soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Participants receive alectinib alone, taken orally twice daily

6 months

Monthly visits for safety and feasibility assessment

Phase 2 Treatment

Participants in Arm A receive alectinib alone; Arm B receives SRS followed by alectinib

24 months

Monthly visits for treatment and monitoring

Follow-up

Participants are monitored for cognitive decline, overall survival, and disease progression

31 months

Treatment Details

Interventions

• Alectinib
• Stereotactic Radiosurgery

Trial Overview The trial tests Alectinib, an oral drug taken twice daily for up to two years. Phase 1b participants receive only Alectinib; in Phase 2, one group continues with just Alectinib while another receives Stereotactic Radiosurgery (SRS) plus Alectinib.

Participant Groups

Group I: Phase 2: Arm B Experimental Treatment 2 Interventions

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

Group II: Phase 2: Arm A Experimental Treatment 1 Intervention

600mg alectinib taken orally twice daily

Group III: Phase 1b: Experimental Experimental Treatment 1 Intervention

600mg alectinib taken orally twice daily

Alectinib is already approved in United States, European Union for the following indications:

Approved in United States as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Approved in European Union as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Who Is Running the Clinical Trial?

Joshua Palmer

Lead Sponsor

Trials

1

Recruited

60+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a study of 34 untreated ALK-positive NSCLC patients with brain metastases, alectinib demonstrated significantly better progression-free survival (PFS) compared to crizotinib, with a median PFS of 32.8 months versus 8.0 months.

Alectinib also showed superior efficacy in treating brain lesions, with a median PFS that was not reached, while crizotinib had a median PFS of 8.5 months, indicating that alectinib may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases: A Retrospective Study. Yin, Q., Li, P., Wang, P., et al.[2022]

In a study of 352 patients with advanced non-small cell lung cancer and brain metastases, the introduction of second-generation ALK inhibitors like alectinib has led to a significant decrease in the use of CNS-directed radiation therapy, with an incidence rate ratio of 0.63 for patients diagnosed after 2017.

Despite the reduced use of local brain treatment, the proportion of patients receiving whole brain radiation therapy remained unchanged, suggesting that while targeted therapies are changing treatment approaches, further research is needed to understand their long-term clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Use of Radiation for Newly Diagnosed Brain Metastases in Patients With ALK-positive Lung Cancer Receiving First-line ALK Inhibitor. Kumar, S., Wang, X., Pittell, H., et al.[2022]

Alectinib is an effective first-line treatment for metastatic ALK-positive non-small cell lung cancer (NSCLC), but it can lead to rare complications such as pneumoperitoneum, as seen in a case involving a 74-year-old female patient.

The pneumoperitoneum in this case was likely due to rapid tumor regression in the gastrointestinal tract, highlighting the need for oncologists to monitor for gastrointestinal perforation when starting treatment with alectinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib-associated pneumoperitoneum in stage IV non-small cell lung cancer - A case report. Maina, RM., Rader, CA., Muenyi, CS., et al.[2022]

Alectinib treatment in patients with ALK-positive non-small-cell lung cancer significantly reduced the cumulative incidence rate of central nervous system (CNS) progression, especially in patients without baseline CNS metastases (8.0% vs 43.9%).

Patients with baseline CNS disease who had prior radiotherapy experienced a higher rate of CNS progression (50.5%) compared to those who were radiotherapy-naive (27.4%), suggesting that alectinib may be particularly beneficial in preventing CNS metastases in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC. Gadgeel, S., Shaw, AT., Barlesi, F., et al.[2019]

Alectinib shows promise as an effective treatment for patients with ALK-driven non-small cell lung cancer who have brain metastasis, even after previous treatments with crizotinib and ceritinib have failed.

This treatment has been associated with durable responses in both brain and other areas of the body, highlighting its potential to improve outcomes for patients facing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of brain metastases with alectinib in anaplastic lymphoma kinase-rearranged lung cancer. Kwok, WC., Tam, TC., Lui, MM., et al.[2021]

In a phase II study involving patients with ALK-positive non-small cell lung cancer, alectinib led to significant improvements in health-related quality of life (HRQoL) across multiple domains, including global health status and fatigue, with improvements observed as early as 6 weeks into treatment.

Patients experienced a rapid median time to symptom improvement of 1.4 months and a delayed time to symptom deterioration of 5.1 months, indicating alectinib's efficacy in managing symptoms and maintaining quality of life, even in those with CNS metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in a phase II, North American study of alectinib in patients with ALK-positive, crizotinib-resistant, non-small cell lung cancer. Ou, SI., Socinski, MA., Gadgeel, S., et al.[2022]

Alectinib, while effective for treating advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements, can lead to serious side effects such as grade 4 hyperbilirubinemia, as seen in a patient after five months of treatment.

After discontinuing alectinib and using an artificial liver support system to manage the hyperbilirubinemia, the patient was successfully treated with ensartinib, achieving stable disease without recurrence of hyperbilirubinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. Peng, L., Xiao, K., Cui, J., et al.[2022]

Alectinib, a targeted therapy for non-small cell lung cancer with ALK mutations, can cause significant side effects, such as a severe maculopapular rash, as demonstrated in a case study of a 63-year-old female patient.

The case highlights the challenges of managing side effects from targeted therapies and emphasizes the importance of documenting such rare reactions to improve future patient care and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib-induced rash unresponsive to desensitization: a case report and literature review. Rodriguez, RR., Dindak, J., Kline, J., et al.[2023]

In a phase 3 trial involving 207 Japanese patients with ALK-positive non-small-cell lung cancer, alectinib demonstrated significantly better progression-free survival compared to crizotinib, with a hazard ratio of 0.34, indicating a strong efficacy advantage for alectinib.

Alectinib also showed a better safety profile, with fewer grade 3 or 4 adverse events (26% vs. 52% for crizotinib) and lower rates of treatment discontinuation due to adverse effects, suggesting it may be a safer first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Hida, T., Nokihara, H., Kondo, M., et al.[2022]

Alectinib is an effective first-line treatment for patients with metastatic ALK+ non-small cell lung cancer (NSCLC), showing significant improvements in survival rates, even for those with brain metastases.

The review highlights alectinib's ability to target ALK gene rearrangements specifically, positioning it as a crucial therapy in the treatment course for ALK+ NSCLC patients, especially after prior treatment with crizotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of alectinib for the treatment of ALK-positive non-small cell lung cancer (NSCLC): patient selection and perspectives. Karachaliou, N., Fernandez Bruno, M., Bracht, JWP., et al.[2020]

Alectinib, a second-generation ALK inhibitor, showed significant improvement in a 50-year-old woman with ALK-positive lung adenocarcinoma who was resistant to crizotinib, particularly in treating leptomeningeal carcinomatosis and spinal cord metastases.

After 3 months of treatment with alectinib, MRI results indicated marked tumor responses in the central nervous system, suggesting that alectinib is a promising option for managing CNS metastases in patients with ALK-positive lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marked improvement in leptomeningeal carcinomatosis and spinal cord metastases following alectinib treatment of crizotinib-resistant, ALK-positive lung adenocarcinoma. Kuribayashi, H., Abe, S., Kuse, N., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases: A Retrospective Study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Real-world Use of Radiation for Newly Diagnosed Brain Metastases in Patients With ALK-positive Lung Cancer Receiving First-line ALK Inhibitor. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Alectinib-associated pneumoperitoneum in stage IV non-small cell lung cancer - A case report. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Control of brain metastases with alectinib in anaplastic lymphoma kinase-rearranged lung cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in a phase II, North American study of alectinib in patients with ALK-positive, crizotinib-resistant, non-small cell lung cancer. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Alectinib-induced rash unresponsive to desensitization: a case report and literature review. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of alectinib for the treatment of ALK-positive non-small cell lung cancer (NSCLC): patient selection and perspectives. [2020]

11. Singapore pubmed.ncbi.nlm.nih.gov

Marked improvement in leptomeningeal carcinomatosis and spinal cord metastases following alectinib treatment of crizotinib-resistant, ALK-positive lung adenocarcinoma. [2020]