ALK Gene TranslocationPhase 1/2NCT02846792

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

A Phase 1/2 study testing Nivolumab and Plinabulin in people with ALK Gene Translocation and EGFR Activating Mutation, run by University of Washington at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: ALK Gene Translocation, EGFR Activating Mutation, Recurrent Non-Small Cell Lung Carcinoma
What is being tested?: Nivolumab and Plinabulin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: 14 Jun 2017to 16 Aug 2018
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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
Abstinence is an acceptable method of birth control
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

Who cannot join

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;

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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
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
Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study
Subjects on chronic systemic steroids for any reason would be excluded from the study; the use of topical steroids is allowable
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

Trial locations and contacts

1 site in 1 country.

United States1 site

Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

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:

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:

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.

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
Being tested: Nivolumab, Plinabulin
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabBiological
Also called Opdivo
Given IV
PlinabulinDrug
Also called NPI-2358
Given IV

Study groups in NCT02846792
Study group	Role	What they receive
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. Receives: Biological: Nivolumab; Drug: Plinabulin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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
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.
Measured: 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
Will be summarized using descriptive statistics (mean, standard deviation, median, minimum and maximum values).
Measured: 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
Will be summarized using descriptive statistics (mean, standard deviation, median, minimum and maximum values).
Measured: Time between receipt of first study drug until death date or last known alive date, assessed up to 16 months
Toxicity Rates
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.
Measured: 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
Assessed using Response Evaluation Criteria in Solid Tumors version 1.1.
Measured: Time between receipt of first study drug until disease progression date, unacceptable toxicity or withdrawal of patient consent, assessed up to 16 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Jun 201716 Aug 2018

First posted27 Jul 2016 (estimated)
Study start14 Jun 2017
Primary completion12 Jul 2018
Study completion16 Aug 2018

Why it stopped: Immunotherapy approved for NSCLC in the first line setting

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for ALK Gene TranslocationStudies of the same condition, open and under way.
More trials run by University of WashingtonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02846792
Sponsor's protocol ID: 9602
Other IDs: NCI-2016-01009, 9602, P30CA015704
Status last verified: Feb 2019
First submitted: 19 Jul 2016
Last updated: 4 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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