Ignite Creation Date:
2024-05-06 @ 12:20 PM
Last Modification Date:
2024-10-26 @ 12:57 PM
Study NCT ID:
NCT03737994
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-07
First Post:
2018-11-09
Brief Title:
Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Biomarker-Driven Protocol for Previously Treated ALK-Positive Non-Squamous NSCLC Patients The NCI-NRG ALK Protocol
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This National Cancer Institute NCI-NRG ALK Protocol phase II trial studies how well a combination of different biomarkerALK 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 biomarkerALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer
Detailed Description:
PRIMARY OBJECTIVES
I To assess whether ALK kinase domain mutations G1202C1156YI1171L1196 V1180 F1174compound 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 ALKL1198FMET 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
I To assess whether ALK kinase domain mutations G1202C1156YI1171L1196 V1180 F1174compound 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 ALKL1198FMET 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA180868 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180868 |
| NCI-2018-02486 | REGISTRY | None | None |
| NRG-LU003 | OTHER | None | None |
| NRG-LU003 | OTHER | None | None |