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Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

This study has been withdrawn prior to enrollment.
(lack of access to study drug)
Information provided by:
Mayo Clinic Identifier:
First received: June 24, 2011
Last updated: December 13, 2012
Last verified: December 2012

This phase I trial studies the side effects and best dose of sirolimus and gold sodium thiomalate when given together in treating patients with advanced squamous non-small cell lung cancer (NSCLC). Sirolimus and gold sodium thiomalate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sirolimus
Drug: gold sodium thiomalate
Other: pharmacological study
Genetic: RNA analysis
Genetic: polymerase chain reaction
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combined PKCiota and mTOR Inhibition for Treatment of Advanced Squamous Lung Cancer

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Maximally tolerated dose (MTD) of ATM plus sirolimus [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD.

Secondary Outcome Measures:
  • To describe the adverse event profile associated with the treatment combination of ATM plus sirolimus. [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Confirmed response rate [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Overall survival time [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
  • Time-to-progression (TTP) [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: June 2011
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive sirolimus PO QD on days 1-28 and gold sodium thiomalate IM on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: sirolimus
Given PO
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Drug: gold sodium thiomalate
Given IM
Other Names:
  • Aurolate
  • Myochrysine
  • sodium aurothiomalate
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Genetic: RNA analysis
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR

Detailed Description:

PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of ATM (gold sodium thiomalate) plus sirolimus. SECONDARY OBJECTIVES: I. To describe the adverse event profile associated with this treatment combination. II. To preliminarily evaluate the response rate, time to progression, progression-free survival and overall survival of patients treated with this treatment combination. TERTIARY OBJECTIVES: I. To evaluate tumor biomarkers of protein kinase C (PKCι) and mammalian Target Of Rapamycin (mTOR) signaling activity as predictors of response to ATM/sirolimus therapy. II. To evaluate the use of surrogate biomarkers of PKCι and mTOR inhibition in peripheral blood lymphocytes (PBLs) to monitor response to ATM/sirolimus therapy. OUTLINE: This is a dose-escalation study. Patients receive sirolimus orally (PO) once daily (QD) on days 1-28 and gold sodium thiomalate intramuscularly (IM) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 3 months.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Cohort I (Dose Escalation) only: must have histologic proof of an advanced, solid tumor that is now unresectable
  • Cohort II (MTD) only
  • Patients must have platinum-refractory NSCLC (platinum-refractory defined as either disease progression either during or within 6 months of completion of first-line platinum-based chemotherapy)
  • Must have measurable disease
  • Must have received at least one prior approved chemotherapeutic regimen unless there is no known, approved therapeutic regimen for their malignancy
  • Must have evidence of disease progression within the preceding 6 months - Absolute neutrophil count (ANC) >= 1500/uL
  • Platelets (PLT) >= 100,000/uL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • (Serum glutamic oxaloacetic transaminase [SGOT]) aspartate aminotransferase (AST) / (serum glutamic pyruvic transaminase [SGPT]) alanine transaminase (ALT) =< 3 x ULN or (SGOT) AST / (SGPT) ALT =< 5 x ULN if liver involvement
  • Creatinine =< 1.5 x ULN
  • Fasting blood glucose =< 126 mg/dL
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic in Florida for follow-up
  • Life expectancy >= 84 days (3 months)
  • Willing to provide blood and tissue samples for correlative research purposes; Note: the goals of this study include assessment of the biologic effects of the agent being tested and are, therefore, contingent upon availability of the biologic specimens
  • Women of childbearing potential only: negative (serum) pregnancy test done =< 7 days prior to registration

Exclusion Criteria:

  • 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
  • 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
  • Known central nervous system (CNS) metastases or seizure disorder; 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
  • Patients with known diabetes mellitus unless well-controlled (fasting blood sugar [FBS] =< 126mg/dL and hemoglobin [Hb]A1C =< 7.0)
  • 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 because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: - 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 (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • 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 =< 168 days (6 months) or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias
  • Known allergy to ATM (Aurothiomalate [gold sodium thiomalate]) or other gold compounds
  • >= Grade 2 hypertriglyceridemia
  • >= Grade 2 hypercholesterolemia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01383668

Sponsors and Collaborators
Mayo Clinic
Principal Investigator: Michael Menefee Mayo Clinic in Florida
  More Information

No publications provided

Responsible Party: Menefee, Michael, Mayo Clinic Cancer Center Identifier: NCT01383668     History of Changes
Other Study ID Numbers: MC102A, NCI-2011-00968
Study First Received: June 24, 2011
Last Updated: December 13, 2012
Health Authority: United States: Federal Government
United States: Institutional Review Board

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Gold Sodium Thiomalate
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 20, 2014