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

NCT02126527 | Withdrawn Phase 1 DMC

• 4 other identifiers: MC1213NCI-2013-0118013-001054P30CA015083
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Recurrent Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• 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)

  28 days

• 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.

  Up to 24 weeks

Secondary Outcomes (7)

• Incidence of adverse events assessed using NCI CTCAE version 4.0

  Up to 2 years

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

  Up to 2 years

• Confirmed and best responses

  Up to 2 years

• Time to progression

  Up to 2 years

• PFS

  Up to 2 years

Study Arms (1)

Treatment (auranofin and sirolimus)

EXPERIMENTAL

Patients 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.

Drug: auranofin; Drug: sirolimus; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

auranofin DRUG

Given PO

Also known as: Ridaura

Treatment (auranofin and sirolimus)

sirolimus DRUG

Given PO

Also known as: AY 22989, Rapamune, rapamycin, SLM

Treatment (auranofin and sirolimus)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (auranofin and sirolimus)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (auranofin and sirolimus)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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 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:

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Auranofin; Sirolimus

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aurothioglucose; Organogold Compounds; Organometallic Compounds; Organic Chemicals; Macrolides; Lactones

Study Officials

• Michael E Menefee, M.D.

  Mayo Clinic campus in Florida

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2014
• First Posted: April 30, 2014
• Study Start: August 1, 2013
• Primary Completion: September 1, 2014
• Last Updated: August 26, 2016

Record last verified: 2014-04

Locations

US (1)