A Multiple-Center, Open-Label, Study of the Safety and Efficacy of Oral NRX 194204 Capsule Administered Daily for a Minimum of 4 Weeks in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
- Male or female, age ≥ 18 years
- Histologically confirmed advanced stage III or IV NSCLC that is recurrent or has
progressed after treatment. Failure on at least 2 NSCLC treatment regimens
- Uni-dimensionally measurable NSCLC defined as at least one lesion that can be
measured in at least one dimension (longest diameter to be recorded) as ≥ 2cm with
conventional techniques or as ≥ 1cm on spiral CT scan.
- Patients are eligible if disease free from previous malignancies, other than a
previous NSCLC, for greater than two years. Patients with a history of prior basal
cell carcinoma of the skin or pre-invasive carcinoma of the cervix are not excluded.
- Karnofsky performance status ≥ 60 (Attachment 14.4) or ECOG performance status 0-2
- Life expectancy > 12 weeks.
- Able to swallow capsule form of the drug.
- Hemoglobin > 8.5 g/dl;
- Platelets > 100,000 cells/mm3;
- Neutrophils > 1500 cells/mm3;
- PT and PTT within normal limits, except for patients receiving Coumadin for
thromboembolic prophylaxis only, in whom INR of less than 2 will be allowable.
- Total bilirubin < 1.5 x ULN;
- AST/ALT < 3.0 x ULN;
- Serum creatinine < 2.0 mg/dl;
- Serum calcium < 11.5 mg/dl;
- Fasting serum triglycerides < 2.5 x ULN.
- Negative urine pregnancy test for women of child-bearing potential at screening and
on Day 1, and agreement by both women and men of reproductive potential to use two
reliable forms of contraception during therapy and for 1 month following
discontinuation of therapy unless abstinence is the chosen birth control method.
- Able to follow study instructions, accessible for treatment and follow-up, and likely
to complete all study requirements.
- Significant medical history or unstable medical condition (congestive heart failure,
recent myocardial infarction within 3 months, unstable angina, active systemic
infection, uncontrolled hypertension). Patients with controlled diabetes will be
- Prior treatment with bexarotene (Targretin) or NRX 194204.
- Current enrollment in an investigational drug or device study or participation in
such a study within 21 days of entry into this study.
- Known sensitivity to any of the ingredients in the study medication.
- Known HIV-positive patients.
- Females who are pregnant, nursing, or planning a pregnancy.
- Major surgery within previous 4 weeks; large field radiation therapy (> 25% of the
patient's total marrow) or chemotherapy (including investigational agents or
participation in another clinical study) within previous 3 weeks; mitomycin C or
nitrosoureas within 6 weeks. In all instances, patients must have fully recovered
from acute toxicities related to prior therapies.
- Systemic retinoid therapy, or Vitamin A at dosages > 15,000 IU per day, during
previous 4 weeks.
- Patients with a history of pancreatitis or at significant risk of developing
pancreatitis (e.g., uncontrolled hyperlipidemia, excessive alcohol consumption,
uncontrolled diabetes mellitus, and medications known to increase triglyceride levels
or to be associated with pancreatic toxicity).
- Primary brain tumors, active brain metastasis including progression from last scan or
evidence of cerebral edema, or clinical symptoms of brain metastasis.
- Condition or situation which, in the investigator's opinion, may put patient at
significant risk, may confound the study results, or may interfere significantly with
patient's participation in the study.