Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer
Extensive Stage Small Cell Lung Carcinoma
Recurrent Non-Small Cell Lung Carcinoma
Recurrent Small Cell Lung Carcinoma
Squamous Cell Lung Carcinoma
Stage IIIA Non-Small Cell Lung Cancer
Stage IIIB Non-Small Cell Lung Cancer
Stage IV Non-Small Cell Lung Cancer
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I-II Trial of Combined PKCι and mTOR Inhibition for Patients With Advanced or Recurrent Lung Cancer (NSCLC and SCLC) Without Standard Treatment Options|
- MTD of auranofin (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]The number and severity of all adverse events (overall and by dose level) will be tabulated and summarized. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
- Number and severity of all adverse events (Phase I) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Number and severity of all adverse events (overall and by dose level) will be tabulated and summarized.
- Progression-free survival rate (Phase II) [ Time Frame: At 4 months ] [ Designated as safety issue: No ]A patient is considered to be a 4-month progression-free survivor, or success, if the patient is 4 months from registration without a documentation of disease progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. Additionally, an estimate and confidence interval for the 4-month progression-free survival rate incorporating censoring may be computed using the method of Kaplan-Meier.
- Survival time [ Time Frame: Defined as the time from registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]The distribution of survival time will be estimated using the method of Kaplan-Meier. The median overall survival time will be descriptively compared to that of the subgroup of patients with squamous cell carcinoma on the cisplatin/gemcitabine arm of Scagliotti et al (2008).
- Progression-free survival time [ Time Frame: From registration to the earliest date of documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier.
- Overall response rate, defined to be either a complete response (CR) or partial response (PR) noted as the objective status [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The overall response rate will be estimated in the subset of patients with measureable disease by the number of responses in evaluable patients with measurable disease divided by the total number of evaluable patients with measureable disease. The appropriate confidence interval will be calculated based on the binomial distribution
- Duration of response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Defined for all evaluable patients with measurable disease who have achieved a response as the date at which the patient's earliest best objective status is first noted to be a CR or PR to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.
- Change in protein kinase C (PKC) iota protein expression [ Time Frame: Baseline to up to 5 years ] [ Designated as safety issue: No ]Will be evaluated at baseline using the baseline tissue specimen and explored in relation to 4-month progression-free survival and subsequently in relation to other clinical outcomes such as tumor response and adverse event incidence using two-way tables and analyzed using Fisher's exact tests.
|Study Start Date:||November 2012|
|Estimated Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (auranofin and sirolimus)
Patients receive auranofin PO on days 1-28 and sirolimus PO on days 1-28 (days 8-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: RidauraDrug: Sirolimus
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Other Name: pharmacological studies
I. To establish the maximum tolerated dose of auranofin plus sirolimus after at least one line of platinum based chemotherapy for lung cancer (squamous, ras-mutated adenocarcinoma, or small cell lung cancer) patients with no acceptable standard treatment options. (Phase I) II. To assess the progression-free survival at four months of patients treated with auranofin after at least one line of platinum based chemotherapy for lung cancer (squamous, ras-mutated adenocarcinoma, or small cell lung cancer) patients with no acceptable standard treatment options. (Phase II)
I. To assess the overall survival in this population in comparison to recent historical controls.
II. To determine the adverse events (AE) profile and safety of the regimen. III. To determine the overall response rate, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria, and duration of tumor response in those patients with measurable disease.
I. To assess the relationship between molecular correlates and progression-free survival (PFS), overall survival (OS), response and adverse events.
OUTLINE: This is a phase I, dose-escalation study of auranofin followed by a phase II study.
Patients receive auranofin orally (PO) on days 1-28 and sirolimus PO on days 1-28 (days 8-28 of course 1). 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 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01737502
|United States, Arizona|
|Mayo Clinic in Arizona||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Helen J. Ross|
|Principal Investigator:||Helen Ross||Mayo Clinic|