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

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ClinicalTrials.gov Identifier: NCT01737502
Recruitment Status : Recruiting
First Posted : November 29, 2012
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE November 27, 2012
First Posted Date  ICMJE November 29, 2012
Last Update Posted Date February 22, 2019
Actual Study Start Date  ICMJE November 29, 2012
Estimated Primary Completion Date August 21, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 14, 2015)
  • MTD of auranofin (Phase I) [ Time Frame: 28 days ]
    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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 28, 2012)
Progression-free survival rate measured by survival out to 4 months. [ Time Frame: At 4 months ]
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.
Change History Complete list of historical versions of study NCT01737502 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2015)
  • Survival time [ Time Frame: Defined as the time from registration to death due to any cause, assessed up to 5 years ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2012)
  • Survival time in this population in comparison to recent historical controls (exemplified by survival of the squamous histology cohort of the Scagliotti et al trial of cisplatin with pemetrexed or gemcitabine for advanced NSCLC). [ Time Frame: Defined as the time from registration to death due to any cause, assessed up to 2 years ]
  • Overall response rate (CR or PR) [ Time Frame: Assessed at 8 week intervals up to 2 years ]
  • Adverse Events (AE) profile and safety of the regimen using the CTCAE v4.0. [ Time Frame: Up to 2 years ]
Current Other Pre-specified Outcome Measures
 (submitted: April 14, 2015)
Change in protein kinase C (PKC) iota protein expression [ Time Frame: Baseline to up to 5 years ]
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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer
Official Title  ICMJE 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
Brief Summary This phase I/II trial studies the side effects and best dose of auranofin when given together with sirolimus and to see how well it works in treating patients with lung cancer that has spread or other places in the body and cannot be cured or controlled by treatment or has come back after a period of time during which the cancer could not be detected. Auranofin and sirolimus may stop or slow the growth of lung cancer.
Detailed Description

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Extensive Stage Small Cell Lung Carcinoma
  • Lung Adenocarcinoma
  • 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
Intervention  ICMJE
  • Drug: Auranofin
    Given PO
    Other Name: Ridaura
  • Drug: Sirolimus
    Given PO
    Other Names:
    • AY 22989
    • RAPA
    • SILA 9268A
    • WY-090217
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
    Other Name: pharmacological studies
Study Arms  ICMJE 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.
Interventions:
  • Drug: Auranofin
  • Drug: Sirolimus
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 14, 2015)
47
Original Estimated Enrollment  ICMJE
 (submitted: November 28, 2012)
41
Estimated Study Completion Date  ICMJE August 21, 2020
Estimated Primary Completion Date August 21, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologic or cytologic confirmation of lung cancer (squamous, ras-mutated adenocarcinoma or small cell lung cancer)
  • Patients must have received at least one course of chemotherapy consisting of a platinum doublet and must have no acceptable standard treatment options
  • Prior radiation therapy is permitted as long as:

    • Recovered from the toxic effects of radiation treatment before study entry, except for alopecia
  • Absolute neutrophil count (ANC) >= 1500 uL
  • Platelets (PLT) >= 100,000 uL
  • Hemoglobin (Hgb) >= 9 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN or SGOT (AST) and SGPT (ALT) =< 5 x ULN is acceptable if liver has tumor involvement
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
  • Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Ability to provide informed consent
  • Life expectancy >= 12 weeks
  • Willing to return to Mayo Clinic enrolling institution for follow-up
  • Willing to provide tissue samples for correlative research purposes

Exclusion Criteria:

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; NOTE: patients with treated CNS metastases without evidence of progression and without uncontrolled symptoms or need for steroids may enroll
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded
  • Unwilling or unable to, comply with the protocol
  • Any of the following prior therapies:

    • Radiation to >= 25% of bone marrow
    • Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; insertion of a vascular access device is not considered major or minor surgery in this regard
  • Any of the following concurrent severe and/or uncontrolled medical conditions:

    • Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
    • Angina pectoris
    • History of congestive heart failure =< 3 months, unless ejection fraction > 40%
    • Myocardial infarction =< 6 months prior to registration
    • Cardiac arrhythmia
    • Poorly controlled diabetes
    • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
    • Active or recent history of hemoptysis; if hemoptysis has resolved with measures such as palliative radiation therapy (e.g. 3000 cGy over 10 fractions), arteriographic embolization or endobronchial interventions (e.g. photodynamic therapy, brachytherapy), etc. for > 14 days, patients may be considered for participation in this study
    • >= Grade 2 hypertriglyceridemia
    • >= Grade 2 hypercholesterolemia
    • Any illness that in the opinion of the investigator would compromise the ability of the patient to participate safely in the clinical trial
  • Use of St. John's Wort because of its effects on hepatic drug metabolism
  • Other active malignancy: EXCEPTIONS: Non-melanoma skin cancer, localized prostate 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)
  • Unable to discontinue use of potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors/inducers
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01737502
Other Study ID Numbers  ICMJE MC1125
NCI-2012-00518 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
11-001987
MC1125 ( Other Identifier: Mayo Clinic in Arizona )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Helen Ross Mayo Clinic
PRS Account Mayo Clinic
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP