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PKCi & mTOR Inhibition With Auranofin+Sirolimus for Squamous Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01737502
First received: November 27, 2012
Last updated: October 24, 2014
Last verified: October 2014
  Purpose

The primary purpose of this study is to find out what effects (good or bad) the drugs auranofin and sirolimus have on patients with lung cancer; to find out if auranofin and sirolimus can stop or slow the growth of the lung cancer; to learn more about how auranafin and sirolimus work against lung cancer by testing blood and tissue samples.


Condition Intervention Phase
Adenosquamous Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: sirolimus
Drug: auranofin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Combined PKCiota and mTOR Inhibition as Maintenance Therapy for Patients With Stage IV Squamous Histology NSCLC Without Progression Following at Least Four Cycles of First-line Platinum Containing Chemotherapy

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Progression-free survival rate measured by survival out to 4 months. [ 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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Overall response rate (CR or PR) [ Time Frame: Assessed at 8 week intervals up to 2 years ] [ Designated as safety issue: No ]
  • Adverse Events (AE) profile and safety of the regimen using the CTCAE v4.0. [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 41
Study Start Date: March 2013
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (auranofin, sirolimus)
Patients receive auranofin and sirolimus PO on days 1-28. 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: auranofin
oral
Other Name: Ridaura

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the progression-free survival at four months of patients treated with maintenance auranafin plus sirolimus after non-progression on first line platinum based chemotherapy for stage IV squamous histology non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To assess the overall survival 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).

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 this population in patients with measurable disease.

TERTIARY OBJECTIVES:

I. To assess the relationship between molecular correlates and progression free survival (PFS), overall survival (OS), response and toxicity.

OUTLINE:

Patients receive auranofin and sirolimus orally (PO) on days 1-28 of each cycle. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months for up to 2 years.

  Eligibility

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

Inclusion Criteria:

Histologic or cytologic confirmation of lung cancer (squamous, Rasmutated 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 and blood samples for correlative research purposes

Exclusion Criteria:

Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

  • 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 because of possible pharmacokinetic interactions with oral investigational agents 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 =< 84 days (3 months), unless ejection fraction > 40%
  • Myocardial infarction =< 168 days (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.
  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 ClinicalTrials.gov identifier: NCT01737502

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Mayo Clinic Clinical Trials Office    855-776-0015      
Principal Investigator: Helen J. Ross         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Helen Ross Mayo Clinic in Arizona
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01737502     History of Changes
Other Study ID Numbers: MC1125, NCI-2012-00518
Study First Received: November 27, 2012
Last Updated: October 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Auranofin
Everolimus
Sirolimus
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

ClinicalTrials.gov processed this record on November 20, 2014