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Recurrent Non-small Cell Lung CancerPhase 1NCT02126527

Auranofin and Sirolimus in Treating Patients With Advanced Solid Tumors or Recurrent Non-Small Cell Lung Cancer

A Phase 1 study testing auranofin, sirolimus and laboratory biomarker analysis in people with Recurrent Non-small Cell Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by Mayo Clinic at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I clinical trial studies the side effects and best dose of auranofin and sirolimus when given together in treating patients with non-small cell lung cancer. Immunosuppressive therapy, such as auranofin and sirolimus, may be an effective treatment for non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
auranofin, sirolimus and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Aug 2013to Sep 2014
Phase
Phase 1
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

  • Cohort I (dose escalation) only: Histologic proof of an advanced, solid tumor that is now unresectable
  • Cohort II (maximum tolerated dose) only:
  • Platinum-refractory non-small cell lung cancer (NSCLC) (platinum-refractory defined as either disease progression either during or within 6 months of completion of first-line platinum-based chemotherapy)
  • Measurable disease
  • Evidence of disease progression =< 6 months prior to registration
  • Received at least one prior approved chemotherapeutic regimen unless there is no known, approved therapeutic regimen for their malignancy
Show all 21Show fewer
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelets (PLT) >= 100,000/mm^3
  • Total bilirubin =< 1.5 upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN (=< 5 x ULN for patients with liver involvement)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN (=< 5 x ULN for patients with liver involvement)
  • Creatinine =< 1.5 x ULN
  • Fasting blood glucose =< 126 mg/dL
  • Fasting triglycerides =< 1.5 x ULN
  • Fasting cholesterol =< 1.5 x ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Ability to provide informed written consent
  • Willing to return to Mayo Clinic in Florida for follow-up (during the active monitoring phase of the study); note: during the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Life expectancy >= 84 days (3 months)
  • Willing to provide tissue and blood samples for correlative research purposes; note: the goals of this study include assessment of the biologic effects on surrogate markers of the agent(s) being tested and are, therefore, contingent upon availability of the biologic specimens
  • Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

Who cannot join

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following prior therapies:
  • Chemotherapy =< 28 days prior to registration
  • Mitomycin C/nitrosoureas =< 42 days prior to registration
  • Immunotherapy =< 28 days prior to registration
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  • Biologic therapy =< 28 days prior to registration
  • Radiation therapy =< 28 days prior to registration
  • Radiation to > 25% of bone marrow
  • Bevacizumab =< 28 days prior to registration
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV cardiovascular disease
  • Central nervous system (CNS) metastases or seizure disorder; NOTE: patients with known brain metastases that have been successfully treated and stable for >= 6 months without requirement for corticosteroids and without seizure activity will be eligible
  • Receiving therapeutic anticoagulation with warfarin; NOTE: prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices is allowed, provided that international normalized ratio (INR) < 1.5; therapeutic anti-coagulation with low molecular weight heparin is allowed at time of registration
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and/or patients known to be human immunodeficiency virus (HIV) positive
  • Cohort II Only: Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, patient must not be receiving other cytotoxic or molecularly targeted therapeutics treatment for their cancer; patients receiving certain hormonal manipulations as part of their treatment may be allowed to continue at the discretion of the principal investigator (PI) (e.g. luteinizing hormone-releasing hormone [LHRH] analogs for prostate cancer); concurrent endocrine therapy for breast cancer will not be permitted
  • History of myocardial infarction or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias =< 168 days (6 months) prior to registration
  • Known allergy to auranofin or other gold compounds
  • Receiving any medications or substances that are strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); NOTE: use of strong inhibitors and inducers is prohibited =< 7 days prior to registration

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

Other trials in United States

About this study

Official title: Phase I Study of Auranofin and Sirolimus in Adult Patients With Non-Small Cell Lung Cancer

This phase I clinical trial studies the side effects and best dose of auranofin and sirolimus when given together in treating patients with non-small cell lung cancer. Immunosuppressive therapy, such as auranofin and sirolimus, may be an effective treatment for non-small cell lung cancer. Sirolimus may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving auranofin and sirolimus may be an effective treatment for non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximally tolerated dose (MTD) of auranofin plus sirolimus (Cohort I).

II. To determine the confirmed response rate of auranofin plus sirolimus (Cohort II).

SECONDARY OBJECTIVES:

  1. To describe the adverse event and toxicity profiles associated with this treatment combination.

II. To evaluate response, time to progression, progression-free survival (PFS), overall survival (OS), and time to treatment failure in patients treated with this treatment combination.

TERTIARY OBJECTIVES:

  1. To evaluate tumor biomarkers of protein kinase C (PKC) and mammalian target of rapamycin (mTOR) signaling activity as predictors of clinical outcome (i.e. response, PFS, OS) for patients receiving auranofin/sirolimus therapy.

II. To evaluate the use of surrogate biomarkers of PKC and mTOR inhibition in peripheral blood lymphocytes (PBLs) as predictors of clinical outcome (i.e. response, PFS, OS) for patients receiving auranofin/sirolimus therapy.

OUTLINE: This is a cohort I, dose-escalation study followed by a cohort II study.

Patients receive auranofin orally (PO) once daily (QD) and sirolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 2 years.

Being tested
auranofin, sirolimus, laboratory biomarker analysis, pharmacological study
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.

  • auranofinDrug

    Also called Ridaura

    Given PO

  • sirolimusDrug

    Also called AY 22989, Rapamune, rapamycin, SLM

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT02126527
Study groupRoleWhat they receive
Treatment (auranofin and sirolimus)ExperimentalPatients receive auranofin PO QD and sirolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: auranofin; Drug: sirolimus; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Cohort I)

    Measured: 28 days

  2. Proportion of confirmed tumor responses assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort II)

    Will be estimated by the number of confirmed responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

    Measured: Up to 24 weeks

Secondary outcomes (7)

  1. Incidence of adverse events assessed using NCI CTCAE version 4.0

    The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.

    Measured: Up to 2 years

  2. Overall toxicity incidence evaluated using the Common Toxicity Criteria (CTC) standard toxicity grading

    Overall toxicity incidence as well as toxicity profiles by dose level, patient, and tumor site will be explored and summarized. Frequency distributions, graphical techniques, and other descriptive measures will form the basis of these analyses.

    Measured: Up to 2 years

  3. Confirmed and best responses

    Will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall, by tumor group, and by cohort).

    Measured: Up to 2 years

  4. Time to progression

    Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).

    Measured: Up to 2 years

  5. PFS

    Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).

    Measured: Up to 2 years

  6. OS

    Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).

    Measured: Up to 2 years

  7. Time to treatment failure

    Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).

    Measured: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed 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 posted30 Apr 2014 (estimated)
  2. Study startAug 2013
  3. Primary completionSep 2014 (estimated)

Why it stopped: no participants enrolled

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 1
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
NCT02126527
Sponsor's protocol ID
MC1213
Other IDs
NCI-2013-01180, 13-001054, P30CA015083
Status last verified
Apr 2014
First submitted
28 Apr 2014
Last updated
26 Aug 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing auranofin, sirolimus and laboratory biomarker analysis in people with Recurrent Non-small Cell Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by Mayo Clinic at 1 site in United States.

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 21 inclusion and 25 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 26 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Cohort I) (time frame: 28 days). The study lists 2 primary outcomes in all. 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 NCT02126527.

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 26 Aug 2016.

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