Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer
Primary Purpose
Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
sirolimus
gold sodium thiomalate
pharmacological study
RNA analysis
polymerase chain reaction
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Non-small Cell Lung Cancer
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (enzyme inhibitor therapy)
Arm Description
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.
Outcomes
Primary Outcome Measures
Maximally tolerated dose (MTD) of ATM plus sirolimus
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.
Confirmed response rate
Overall survival time
Progression-free survival (PFS)
Time-to-progression (TTP)
Full Information
NCT ID
NCT01383668
First Posted
June 24, 2011
Last Updated
March 30, 2020
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01383668
Brief Title
Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer
Official Title
Combined PKCiota and mTOR Inhibition for Treatment of Advanced Squamous Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Withdrawn
Why Stopped
lack of access to study drug
Study Start Date
June 2011 (undefined)
Primary Completion Date
February 8, 2013 (Actual)
Study Completion Date
February 8, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (enzyme inhibitor therapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
sirolimus
Other Intervention Name(s)
AY 22989, Rapamune, rapamycin, SLM
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
gold sodium thiomalate
Other Intervention Name(s)
Aurolate, Myochrysine, sodium aurothiomalate
Intervention Description
Given IM
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
RNA analysis
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
polymerase chain reaction
Other Intervention Name(s)
PCR
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Maximally tolerated dose (MTD) of ATM plus sirolimus
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
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
Title
Confirmed response rate
Time Frame
Every 6 weeks
Title
Overall survival time
Time Frame
Up to 3 months after completion of study treatment
Title
Progression-free survival (PFS)
Time Frame
Up to 3 months after completion of study treatment
Title
Time-to-progression (TTP)
Time Frame
Up to 3 months after completion of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Menefee
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer
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