ALK Inhibitors for Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+566 other locations

Overseen by Jessica J Lin

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This National Cancer Institute (NCI)-NRG ALK Protocol phase II trial studies how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK positive non-squamous non-small cell lung cancer. Lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether a combination of biomarker/ALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer.

Research Team

Jessica J Lin

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for stage IV ALK positive non-squamous NSCLC patients who have progressed after one second-generation ALK inhibitor. They must not have had prior lorlatinib or more than one cycle of chemotherapy at diagnosis without progression. Participants need functioning major organs, no significant heart issues, and can't be pregnant or breastfeeding. Eligible individuals should not have other active cancers or serious illnesses that could affect safety.

Inclusion Criteria

I am not on medications that would interfere with the study drug.

I have brain metastases but also have a measurable cancer lesion outside the brain.

I have brain metastases but no symptoms, or they are treated, and I have stable health.

Exclusion Criteria

I do not have serious heart problems like uncontrolled high blood pressure or recent heart attacks.

I have ongoing or repeated pancreatitis confirmed by tests.

I do not have any serious illness or organ problems that could affect my safety or the study.

Treatment Details

Interventions

• Alectinib (ALK Inhibitor)
• Brigatinib (ALK Inhibitor)
• Carboplatin (Platinum-based Chemotherapy)
• Ceritinib (ALK Inhibitor)
• Cisplatin (Platinum-based Chemotherapy)
• Crizotinib (ALK Inhibitor)
• Ensartinib (ALK Inhibitor)
• Lorlatinib (ALK Inhibitor)
• Pemetrexed (Antimetabolite)

Trial Overview The study tests combinations of biomarker/ALK inhibitors (Lorlatinib, Ceritinib, Alectinib, Brigatinib, Ensartinib, Crizotinib) against standard chemotherapy drugs (Pemetrexed, Cisplatin, Carboplatin) in treating advanced lung cancer with specific genetic changes. It aims to determine which treatment method is more effective.

Participant Groups

Group I: V1180 Experimental Treatment 3 Interventions

Patients with V1180 mutation receive either lorlatinib PO QD, ceritinib PO QD, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: No ALK-resistance mutations Experimental Treatment 8 Interventions

Patients with no ALK-resistant mutations receive either lorlatinib PO QD, ceritinib PO QD, alectinib PO BID, brigatinib PO QD, ensartinib PO QD, or pemetrexed IV over 10 minutes on day 1 with or without either cisplatin IV or carboplatin IV on day 1. ALK inhibitor cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Pemetrexed-based treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Maintenance treatment of pemetrexed may continue until disease progression or unacceptable toxicity.

Group III: MET amplification Experimental Treatment 1 Intervention

Patients with MET amplification receive crizotinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group IV: L1196 (including L1196M) Experimental Treatment 6 Interventions

Patients with L1196 (including L1196M) mutation receive either lorlatinib PO QD, ceritinib PO QD, alectinib PO BID, brigatinib PO QD, or ensartinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group V: I1171 Experimental Treatment 3 Interventions

Patients with I1171 mutation receive either lorlatinib PO QD, ceritinib PO QD, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group VI: G1202 (including G1202del and G1202R) Experimental Treatment 2 Interventions

Patients with G1202 (including G1202del and G1202R) receive either lorlatinib PO QD or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group VII: F1174 Experimental Treatment 3 Interventions

Patients with F1174 receive either lorlatinib PO QD, alectinib PO BID, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group VIII: Compound mutation Experimental Treatment 1 Intervention

Patients with a compound mutation receive lorlatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group IX: C1156Y Experimental Treatment 3 Interventions

Patients with Cy1156Y mutation receive either lorlatinib PO QD, alectinib PO BID, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group X: ALK L1198F mutation (alone or combination with ALK inhibitor) Experimental Treatment 1 Intervention

Patients with ALK L1198F mutation (alone or in combination with another ALK mutation) receive crizotinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Stephanie Gaillard

NRG Oncology

Chief Medical Officer

MD from Johns Hopkins University

Norman Wolmark

NRG Oncology

Chief Executive Officer since 2023

MD from Harvard Medical School