Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer
Last updated on July 2021Recruitment
- Recruitment Status
- Active, not recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Lung Non-Squamous Non-Small Cell Carcinoma
- Stage IV Lung Cancer AJCC v8
- Stage IVA Lung Cancer AJCC v8
- Stage IVB Lung Cancer AJCC v8
- Type
- Interventional
- Phase
- Phase 2
- Design
- Allocation: RandomizedIntervention Model: Parallel AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
PRIMARY OBJECTIVES: I. To assess whether ALK kinase domain mutations (G1202/C1156Y/I1171/L1196/ V1180/ F1174/compound mutation) associated with drug resistance are prognostic for objective response to subsequent ALK inhibitor therapy. II. To assess whether subsequent pemetrexed based chemotherapy im...
PRIMARY OBJECTIVES: I. To assess whether ALK kinase domain mutations (G1202/C1156Y/I1171/L1196/ V1180/ F1174/compound mutation) associated with drug resistance are prognostic for objective response to subsequent ALK inhibitor therapy. II. To assess whether subsequent pemetrexed based chemotherapy improves objective response comparing to ALK inhibitor therapy for no ALK mutation patients. III. To evaluate objective responses of patients with specific genetic alterations (ALKL1198F/MET double mutation or high-level MET gene amplification) treated with crizotinib. SECONDARY OBJECTIVES: I. Progression-free survival (PFS). II. Duration of response (DOR). III. Overall survival (OS). IV. Intracranial objective response rate (ORR). V. Safety and tolerability. CORRELATIVE SCIENCE OBJECTIVE: I. Establish concordance between tumor and liquid biopsies. OUTLINE: Patients with a G1202R or G1202del mutation receive either lorlatinib orally (PO) once daily (QD) or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with a C1156Y mutation receive either lorlatinib PO QD, brigatinib PO QD, or alectinib PO twice daily (BID). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with a 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. Patients with a L1196 mutation receive either lorlatinib PO QD, brigatinib PO QD, ensartinib PO QD, alectinib PO BID, or ceritinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with a V1180 mutation receive either lorlatinib PO QD, brigatinib PO QD, or ceritinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with a F1174 mutation receive either alectinib PO BID, lorlatinib PO QD, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with a compound mutation receive lorlatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with an ALK L1198F mutation alone or with another mutation, and patients with high level MET amplification receive crizotinib PO BID. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with no ALK-resistant mutations receive either lorlatinib PO QD, ceritinib PO QD, alectinib PO BID, brigatinib PO QD, or ensartinib PO QD, or pemetrexed intravenously (IV) over 10 minutes on day 1 and 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. After completion of study treatment, patients are followed up for 30 days, every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.
Tracking Information
- NCT #
- NCT03737994
- Collaborators
- NRG Oncology
- Investigators
- Principal Investigator: Jessica Lin NRG Oncology