Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lymphoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Crizotinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive crizotinib PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Clinical Observation

Laboratory Biomarker Analysis

Site Public Contact

Alison K. Conlin

Nicholas DiBella

Helen J. Ross

John A. Ellerton

Richard L. Deming

Aaron S. Mansfield

Linda L. Garland

Jay W. Carlson

Edward T. Robbins

Eric C. McGary

Tatjana Kolevska

Edmund W. Tai

Shahzad Siddique

Uzair B. Chaudhary

Gigi Q. Chen

Erminia Massarelli

Lisa Bailey

William E. Lawler

Lyudmila A. Bazhenova

Hamid R. Mirshahidi

Pankaj Gupta

Tianhong Li

Timothy E. Byun

Heather A. Wakelee

Davood Vafai

David Gerber

This randomized phase III trial studies how well crizotinib works in treating patients with stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation in a protein called anaplastic lymphoma kinase (ALK). Mutations, or changes, in ALK can make it very active and important for tumor cell growth and progression. Crizotinib may stop the growth of tumor cells by blocking the ALK protein from working. Crizotinib may be an effective treatment for patients with non-small cell lung cancer and an ALK fusion mutation.

PRIMARY OBJECTIVES:

I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) for patients with stage IB \>= 4 cm, II and IIIA, ALK-positive non-small cell lung cancer (NSCLC) following surgical resection.

SECONDARY OBJECTIVES:

I. To evaluate and compare disease-free survival (DFS) associated with crizotinib.

II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.

III. To collect tumor tissue and blood specimens for future research.

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

ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo observation.

After completion of study treatment, patients are followed up every 6 months if \< 4 or 5 years from study entry, and every 12 months if 5-10 or 6-10 years from study entry.

Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)

A Randomized Phase III Trial for Surgically Resected Early Stage Non-small Cell Lung Cancer: Crizotinib Versus Observation for Patients With Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

Distribution will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. The primary comparison will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 5%. Other comparisons of groups will be made using the logrank test and Cox modeling. Estimate will be accompanied by the corresponding 90% confidence intervals.

Distribution will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. Estimate will be accompanied by the corresponding 90% confidence intervals.

Toxicity rates will be compared using Fisher?s exact tests with a one-sided type I error rate of 5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Symptoms and General Pathology

Recurrence

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive plinabulin IV over 30 minutes and nivolumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Plinabulin

Rafael Santana-Davila

This phase I/II trial studies the side effects and best dose of plinabulin when given together with nivolumab and to see how well they work in treating patients with stage IIIB-IV non-small cell lung cancer that has come back or spread to other places in the body. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as plinabulin, 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. Giving nivolumab and plinabulin together may work better at treating patients with non-small cell lung cancer.

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of the combination of nivolumab and plinabulin. (Phase I)

II. To determine the overall response rate (ORR) of treatment with nivolumab with the addition of plinabulin in the treatment of advanced stage non-small cell lung cancer in the second line setting. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the progression free survival (PFS), disease control rate (DCR), duration of response (DOR) and overall survival (OS) of patients treated with nivolumab in combination with plinabulin.

II. To determine the safety and tolerability of the combination of plinabulin and nivolumab.

TERTIARY OBJECTIVES:

I. Patients who have a pre-treatment and/or post cycle one biopsy will have flow cytometry of their tissue to identify infiltration of immune cells, rates of expression of programmed cell death 1 (PD-1), programmed cell death 2 (PD-2) and programmed cell death 1 ligand 1 (PDL1).

OUTLINE: This is a phase I, dose-escalation study of plinabulin followed by a phase II study.

Patients receive plinabulin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days.

Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer

A Phase I/II Clinical Trial of Nivolumab and Plinabulin for Patients With Advanced Stage Non-small Cell Lung Cancer That Have Progressed Through First Line Platinum Doublet Chemotherapy

Defined as no more than 1 of 6 patients experiencing a dose limiting toxicity, graded according to the National Cancer Institute Common Toxicity Criteria version 4.0.

Defined as the sum of complete and partial responses for more than 8 weeks according to Response Evaluation Criteria in Solid Tumors version 1.1.

Defined as the proportion of patients with complete response, partial response, and stable disease for more than 8 weeks according to Response Evaluation Criteria in Solid Tumors version 1.1.

Will be summarized using descriptive statistics (mean, standard deviation, median, minimum and maximum values).

Overall Percentage and number of patients experiencing grade 3 or higher severity of adverse events, graded using the National Cancer Institute Common Toxicity Criteria version 4.0.

Assessed using Response Evaluation Criteria in Solid Tumors version 1.1.

University of Washington

Any adverse events leading to a treatment interruption or dose reduction along with all adverse events that are grade 3 and higher were recorded.

Patients receive plinabulin IV over 30 minutes and nivolumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Nivolumab: Given IV

Plinabulin: Given IV

Treatment (Plinabulin, Nivolumab)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline participant measures are based on total eligible, consented and treated patients.

Study terminated (stopped prematurely), due to immunotherapy approved for NSCLC in the first line setting. Participant flow, Baseline Characteristics and Adverse Events recorded for 5 patients treated on study.

Research Manager

Study terminated (stopped prematurely). Immunotherapy approved for NSCLC in the first line setting.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)	NCT02201992	ALK Gene Rearra... ALK Gene Transl... ALK Positive Stage IB Non-Sm... Stage II Non-Sm... Stage IIA Non-S... Stage IIB Non-S... Stage IIIA Non-...	Clinical Observ... Crizotinib Laboratory Biom...	18 Years -	Eastern Cooperative Oncology Group
Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer	NCT02846792	ALK Gene Transl... EGFR Activating... Recurrent Non-S... ROS1 Gene Trans... Stage IIIB Non-... Stage IV Non-Sm...	Nivolumab Plinabulin	18 Years -	University of Washington
Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)	NCT02201992	ALK Gene Rearra... ALK Gene Transl... ALK Positive Stage IB Non-Sm... Stage II Non-Sm... Stage IIA Non-S... Stage IIB Non-S... Stage IIIA Non-...	Clinical Observ... Crizotinib Laboratory Biom...	18 Years -	Eastern Cooperative Oncology Group
Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer	NCT02846792	ALK Gene Transl... EGFR Activating... Recurrent Non-S... ROS1 Gene Trans... Stage IIIB Non-... Stage IV Non-Sm...	Nivolumab Plinabulin	18 Years -	University of Washington

Spots Global Cancer Trial Database for alk gene translocation