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About
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.
Full description
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.
Enrollment
Sex
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Volunteers
Inclusion criteria
Subjects must have histologically or cytologically-documented stage IIIB or stage IV, recurrent, or metastatic non-small cell lung cancer (NSCLC)
Subjects must have received prior platinum doublet based treatment
Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Subjects, including those in the dose-escalation portion of the study, must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; imagining must be within 28 days of trial enrollment
Absolute neutrophil count (ANC) >= 1000/mm^3
Platelets >= 75,000/dL
Hemoglobin >= 9 g/dL
Total bilirubin =< 1.5 mg/dL x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin =< 3.0 mg/dL)
Serum creatinine =< 1.5 mg/dL or creatinine clearance >= 60 mL/min
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times the upper limit of normal if no liver involvement or =< 5 times the upper limit of normal with liver involvement
For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control throughout the trial starting with the screening visit through 120 days after the last dose of study medication
Male subjects with a female partner(s) of child-bearing potential must agree to use acceptable birth control throughout the trial starting with the screening visit through 120 days after the last dose of study medication
Capability to understand and comply with the protocol requirements as and signed informed consent documents
Exclusion criteria
Systemic anticancer therapy within 21 days of the first dose of study drug
Prior treatment with nivolumab or any other PD1/PDL1 checkpoint inhibitor
Major medical conditions that might affect study participation (e.g. uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled serious infection, cardiac disease)
Significant cardiac history:
History of hemorrhagic diarrhea, inflammatory bowel disease or active uncontrolled peptic ulcer disease; (concomitant therapy with ranitidine or its equivalent and/or omeprazole or its equivalent is acceptable); history of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility
Subjects with untreated symptomatic central nervous system (CNS) metastases are excluded
Subjects are eligible if symptomatic CNS metastases are treated and subjects have neurologically returned to baseline (except for residual signs and symptoms related to CNS treatment) for at least 7 days prior to first dose of study treatment
Subjects with leptomeningeal disease are excluded
Subjects with planned radiation therapy to a target lesion will be excluded
Radiation therapy within 14 days of the first dose of study drug
Subjects who are pregnant or breastfeeding are excluded
Subjects who are unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee are excluded
Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis are excluded
Subject who have active non-infectious pneumonitis
Subjects who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
Subjects with any active, known, or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
Any known additional malignancy (with exception of non-melanoma skin cancer, in-situ breast cancer or a malignancy diagnosed >= 3 years ago and with no evidence of requiring active treatment)
Patients with known active hepatitis B, or hepatitis C will be excluded
Patients with risk factors for bowel obstruction or bowel perforation (e.g., acute diverticulitis) will be excluded
Has any serious or uncontrolled active infection
Primary purpose
Allocation
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5 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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