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

NCT02846792 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 9602NCI-2016-01009P30CA015704
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ALK Gene Translocation; EGFR Activating Mutation; Recurrent Non-Small Cell Lung Carcinoma; ROS1 Gene Translocation; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Plinabulin and Nivolumab (Phase I)

  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.

  Up to 28 days

• Overall Response Rate (Phase II)

  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.

  Time between receipt of first study drug until disease progression date, unacceptable toxicity or withdrawal of patient consent, assessed up to 16 months

Secondary Outcomes (5)

• Disease Control Rate

  Time between receipt of first study drug until disease progression date, unacceptable toxicity or withdrawal of patient consent, assessed up to 16 months

• Duration of Response

  Time between receipt of first study drug until disease progression date, unacceptable toxicity or withdrawal of patient consent, assessed up to 16 months

• Overall Survival

  Time between receipt of first study drug until death date or last known alive date, assessed up to 16 months

• Toxicity Rates

  Adverse events collected from the time patient received the first dose of study therapy through 28 days following the last dose of study therapy or the start of a new cancer therapy, whichever occurred first, assessed up to 28 days post therapy.

• Progression Free Survival

  Time between receipt of first study drug until disease progression date, unacceptable toxicity or withdrawal of patient consent, assessed up to 16 months

Study Arms (1)

Treatment (plinabulin, nivolumab)

EXPERIMENTAL

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.

Biological: Nivolumab; Drug: Plinabulin

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: Opdivo

Treatment (plinabulin, nivolumab)

Plinabulin DRUG

Given IV

Also known as: NPI-2358

Treatment (plinabulin, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Up to 2 lines of prior systemic therapy for metastatic disease are permitted
• Adjuvant chemotherapy or concurrent chemoradiation for early stage disease does not count as prior therapy unless subject progressed within 6 months of completion of regimen
• Patients with known activating mutations in epidermal growth factor receptor (EGFR), or known translocation in anaplastic lymphoma kinase (ALK) or ROS-1 are eligible provided they have progressed on or were intolerant to Food and Drug Administration (FDA) approved targeted therapy
• 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
• Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site prior to 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

You may not qualify if:

• Systemic anticancer therapy within 21 days of the first dose of study drug
• All adverse events from prior systemic therapy must have either stabilized or returned to baseline
• 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 myocardial infarction or ischemic heart disease within 1 year before first study drug administration;
• Uncontrolled arrhythmia;
• History of congenital QT prolongation;
• New York Heart Association class III or IV cardiac disease;
• Uncontrolled hypertension: blood pressure consistently greater than 150 mm Hg systolic and 100 mm Hg diastolic in spite of antihypertensive medication
• 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 must be off corticosteroids for at least 7 days prior to first dose of study treatment
• Subjects with leptomeningeal disease are excluded

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; NPI 2358

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

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.

Results Point of Contact

• Title: Research Manager
• Organization: University of Washington

smasters@seattlecca.org

206-606-7445

Study Officials

• Rafael Santana-Davila

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 27, 2016
• Study Start: June 14, 2017
• Primary Completion: July 12, 2018
• Study Completion: August 16, 2018
• Last Updated: March 4, 2019
• Results First Posted: March 4, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)