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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

Phase 2
18 Years
Open (Enrolling)
Adenosquamous Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

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Trial Information

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


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).


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.


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


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

Inclusion Criteria:

Histologic or cytologic confirmation of stage IV NSCLC with squamous features; NOTE: Mixed
histology allowed if all components consistent with NSCLC; patients whose tumors have
squamous cell histology/features are eligible Patients must have received one course of
chemotherapy consisting of at least four cycles of a platinum doublet with no evidence of
disease progression at study entry

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 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 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 >

- 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 Use of St. John's Wort because of its effects on
hepatic drug metabolism Other active malignancy =< 5 years prior to registration;
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); concurrent
endocrine therapy for breast cancer will not be permitted Unable to discontinue use
of potent cytochrome P450 3A4 (CYP3A4) inhibitors/inducers

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival rate measured by survival out to 4 months.

Outcome Description:

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.

Outcome Time Frame:

At 4 months

Safety Issue:


Principal Investigator

Helen Ross

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic in Arizona


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

Related Keywords:

  • Adenosquamous Cell Lung Cancer
  • Recurrent Non-Small Cell Lung Cancer
  • Squamous Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404