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Recurrent Non-Small Cell Lung CarcinomaPhase 2NCT03023904

Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads

A Phase 2 study testing Nivolumab and Laboratory Biomarker Analysis in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IV Non-Small Cell Lung Cancer, run by Vanderbilt-Ingram Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies how well nivolumab works in treating patients with stage IV lung cancer or that has come back after initial treatment who has high mutation loads. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
29 Dec 2017to 30 Jul 2020
Phase
Phase 2
Are there results?
None posted in the registry

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

  • • Signed written informed consent
  • Subjects must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines; this must be obtained before the performance of any protocol related procedures that are not part of normal subject care
  • Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • Subjects with histologically confirmed stage IV or recurrent NSCLC (per the 7th International Association for the Study of Lung Cancer classification squamous or nonsquamous histology, with no prior systemic anticancer therapy (including EGFR and ALK inhibitors) given as primary therapy for advanced or metastatic disease
  • Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration is at least 2 months prior to enrollment
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  • Prior definitive chemoradiation for locally advanced disease is also permitted as long as the last administration of chemotherapy or radiotherapy (whichever was given last) occurred at least 2 months prior to enrollment
  • Mutation load determined by FoundationOne of >= 20 mutations/MB tested on archival tumor sample; the mutation load metric will be displayed on the FoundationOne report for all participating sites as "tumor mutation burden (TMB) - high" or may be obtained from Foundation Medicine from older reports using the Insights Portal, which will be available to all participating sites, or by emailing Foundation Medicine
  • Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria
  • Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site after the completion of radiation therapy
  • Prior palliative radiotherapy to non-central nervous system (CNS) lesions must have been completed at least 2 weeks prior to enrollment; subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of enrollment are strongly encouraged to receive palliative radiotherapy prior to enrollment
  • White blood cell (WBC) > 2000/uL
  • Neutrophils > 1500/uL
  • Platelets > 100 x 10^9/uL
  • Hemoglobin > 9.0 g/dL
  • Serum creatinine =< 2 x upper limit normal (ULN) or creatinine clearance (CrCl) >= 30 mL/min using the Cockcroft-Gault formula
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (unless liver metastases, who can have AST/ALT =< 5 x ULN)
  • Total bilirubin =< 3 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Women must not be breastfeeding
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of nivolumab
  • "Women of childbearing potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
  • Menopause is defined as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; if menopausal status is considered for the purpose of evaluating childbearing potential, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level > 40 mIU/mL, in order to be considered postmenopausal and not of childbearing potential
  • Women of child bearing potential (WOCBP) and men able to father children who are sexually active with WOCBP must agree to use acceptable contraception
  • Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception
  • Women of childbearing potential receiving nivolumab will be instructed to use and must be willing to use appropriate method(s) of contraception for a period of 23 weeks after the last dose of investigational product
  • Men receiving nivolumab who are sexually active with WOCBP will be instructed to use and must be willing to use acceptable contraception for a period of 31 weeks after the last dose of investigational product

Who cannot join

  • Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded; all subjects with non-squamous histology must have been tested for EGFR mutation status; use of a Food and Drug Administration (FDA)-approved test is strongly encouraged
  • Subjects with known ALK translocations which are sensitive to available targeted inhibitor therapy are excluded; if tested, use of an FDA-approved test is strongly encouraged; subjects with unknown or indeterminate ALK status may be enrolled
  • Active brain metastases or leptomeningeal metastases (carcinomatous meningitis); subjects with brain metastases are eligible if these have been treated and there is no evidence of progression for at least 2 weeks after treatment is complete and corticosteroid dose is stable (and equivalent dose of < 10 mg prednisone) for at least 2 weeks
  • Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before enrollment
  • Subjects with an 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 a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first study treatment with nivolumab; inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
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  • Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration
  • Subjects with previous or active malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to enrollment and no additional therapy is required or anticipated to be required during the study period
  • History of allergy to study drug components or of severe hypersensitivity reaction to any monoclonal antibody
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

About this study

This phase II trial studies how well nivolumab works in treating patients with stage IV lung cancer or that has come back after initial treatment who has high mutation loads. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

SECONDARY OBJECTIVES:

  1. To assess the progression-free survival (PFS). II. To assess the overall survival (OS). III. To correlate response and mutation load with PD-L1 status (5% and 1% cutoffs).

IV. To assess clinical benefit (responses and stable disease lasting >= 6 months).

  1. To assess the response rate in mutation-defined subgroups, including subjects with >= 25 mutations/mutational burden (MB) and >= 30 mutations/MB.

VI. To correlate the type of mutations with response.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 2 weeks for up to 2 years (104 weeks) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 35 days and then every 3 months for 2 years.

Being tested
Nivolumab, Laboratory Biomarker Analysis
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

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT03023904
Study groupRoleWhat they receive
Treatment (nivolumab)ExperimentalPatients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 2 weeks for up to 2 years (104 weeks) in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Nivolumab; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Objective Response Rate defined as the number of subjects with a best overall response of complete response or partial response divided by the number of subjects that receive nivolumab as assessed by RECIST 1.1

    Measured: Up to 6 months

Secondary outcomes (5)

  1. Overall survival

    Measured: From date of enrollment to date of death due to any cause, assessed up to 2 years

  2. Progression Free Survival as determined by RECIST 1.1

    Measured: From date of enrollment until first date of documented progression or death due to any cause, assessed up to 2 years

  3. Mutation load as determined by FoundationOne testing

    Measured: Up to 2 years

  4. Incidence of adverse events (AEs) graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

    Measured: Up to 100 days after the last dose of study drug

  5. PD-L1 expression as determined by immunohistochemistry

    Measured: Up to 2 years

Timeline

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

  1. First posted18 Jan 2017 (estimated)
  2. Study start29 Dec 2017
  3. Primary completion30 Jul 2019 (estimated)
  4. Study completion30 Jul 2020 (estimated)

Why it stopped: Research cancelled

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03023904
Sponsor's protocol ID
VICC THO 16117
Other IDs
NCI-2017-00047
Status last verified
Apr 2018
First submitted
10 Jan 2017
Last updated
25 Apr 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Laboratory Biomarker Analysis in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IV Non-Small Cell Lung Cancer, run by Vanderbilt-Ingram Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate defined as the number of subjects with a best overall response of complete response or partial response divided by the number of subjects that receive nivolumab as assessed by RECIST 1.1 (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03023904.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2018.

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