Clinical trial NCT02134912
Conditions: Adenocarcinoma of the Lung Large Cell Lung Cancer Recurrent Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer
Sponsor: SWOG Cancer Research Network
Start date: 2014-08-01; Completion date: 2016-09-01
Enrollment: 1 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This randomized phase II trial studies how well pemetrexed disodium with or without crizotinib works in treating patients with stage IV non-small cell lung cancer that has progressed after crizotinib. Drugs used in chemotherapy, such as pemetrexed disodium, 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. Crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving pemetrexed disodium is more effective with or without crizotinib in treating patients with non-small cell lung cancer that has progressed after crizotinib.

Detailed description:
PRIMARY OBJECTIVES:

I. To evaluate the efficacy of the combination of crizotinib and pemetrexed (pemetrexed disodium) compared to pemetrexed monotherapy as measured by progression-free survival (PFS) in anaplastic lymphoma kinase (ALK)+ non-squamous non-small cell lung cancer (NSCLC) patients who achieved clinical benefit with crizotinib monotherapy and subsequently progressed systemically.

SECONDARY OBJECTIVES:

I. To compare the response rate (confirmed and unconfirmed, complete and partial responses) in patients randomized to receive pemetrexed monotherapy to historical data.

II. To assess overall survival in both arms. III. To evaluate the patterns of failure (central nervous system \[CNS\], extra-CNS) of the combination of crizotinib and pemetrexed and of pemetrexed monotherapy in ALK+ non-squamous NSCLC after progression on crizotinib.

IV. To evaluate the frequency and severity of toxicities resulting from the administration of crizotinib and pemetrexed compared to pemetrexed monotherapy.

V. To evaluate PFS and the response rate in patients treated with crizotinib following progression on the pemetrexed monotherapy arm.

TERTIARY OBJECTIVES:

I. To compare progression-free survival (PFS) and response rates (RR) between ALK dominant and ALK non-dominant patients in the entire study population and within each treatment arm.

II. To evaluate if the magnitude of difference in these outcomes between ALK dominant and ALK non-dominant patients varies by treatment arm.

III. To assess blood biomarkers of sensitivity and resistance to crizotinib and pemetrexed in an exploratory manner. The blood biomarkers include cell free circulating deoxyribonucleic acid (DNA), micro ribonucleic acid (microRNA) before treatment, during treatment (after 2 cycles) and at treatment progression.

IV. To assess pharmacogenomic factors in peripheral blood that might affect the drug level and treatment outcomes in an exploratory manner.

V. To assess proteomic/immunologic parameters that might affect the treatment outcomes in an exploratory manner.

VI. To evaluate the frequency of individual mechanisms of resistance (copy number gain \[CNG\], mutation, alternate oncogene).

VII. To identify alternative driver mechanisms in ALK fluorescence in situ hybridization positive (FISH+) otherwise unknown.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21 and pemetrexed disodium intravenously (IV) over 10 minutes on day 1.

ARM II: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Upon disease progression or symptomatic deterioration, patients may crossover to Arm I.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Arms: arm 1: Patients receive crizotinib PO BID on days 1-21 and pemetrexed disodium IV over 10 minutes on day 1. arm 2: ARM II: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Upon disease progression or symptomatic deterioration, patients may crossover to Arm I.
Interventions: intervention 1: crizotinib intervention 2: pemetrexed disodium intervention 3: laboratory biomarker analysis intervention 4: pharmacological study
Intervention descriptions: intervention 1: Given PO intervention 2: Given IV intervention 3: Correlative studies intervention 4: Correlative studies

Protocol documents: