RTA 408 in the Treatment of Advanced Solid Tumors (NSCLC & Melanoma) - DISCOVER (DISCOVER)

This is an interventional treatment trial for Metastatic or Incurable Non-small Cell Lung Cancer focused on measuring RTA 408, RTA 408 Capsules, Non-small cell lung cancer, Metastatic non-small cell lung cancer, Incurable non-small cell lung cancer, Refractory melanoma, Relapsed melanoma Read More

Inclusion Criteria:

1. Adult male and female patients (18 to 75 years of age, inclusive);
2. Histologically or cytologically documented advanced NSCLC who have Stage IIIB/Stage IV disease, or recurrent disease following radiation therapy or surgical resection or advanced, unresectable (Stage III) or metastatic (Stage IV) melanoma;
3. Patients must have experienced disease recurrence or progression during or after prior treatment with one or more prior standard systemic therapies;
4. Patients with epidermal growth factor receptor (EGFR) overactivity mutations or anaplastic lymphoma kinase (ALK) rearrangements must have received tyrosine-kinase inhibitor (TKI) therapy prior to consideration for enrollment;
5. Life expectancy > 3 months;
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
7. Have discontinued previous treatments for cancer and recovered from all acute toxic effects of prior systemic therapy (except alopecia) to grade ≤1;

8. Have adequate bone marrow reserve and organ function at screening as follows:

   1. Hematologic: Absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L, hemoglobin ≥ 9 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. The first dose of study drug must not begin until 5 days after the erythrocyte transfusion);
   2. Hepatic: total bilirubin ≤ 1.5 X ULN, ALT and AST ≤ ULN;
   3. Renal: estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) formula ≥ 50 mL/min;
9. Willing to practice methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) from screening through 3 months after taking the final dose of RTA 408;
10. Female patients of childbearing potential must be non-pregnant, non-lactating, and have a negative pregnancy test result prior to enrollment in the study;

Exclusion Criteria:

1. Concurrent active malignancy other than adequately treated nonmelanomatous cell skin cancers, superficial bladder cancer, or carcinoma in situ of the cervix or breast;

2. Patients who previously had brain metastases (screening not required) unless they have met all of the following criteria:

   1. Patient had a resection and/or completed a course of cranial irradiation; and
   2. Patient has no worsening central nervous system symptoms; and
   3. Patient has discontinued all corticosteroids for that indication for at least 2 weeks;

3. Cardiovascular abnormalities:

   1. Evidence of poor cardiovascular function defined as b-type natriuretic peptide (BNP) > 100 pg/mL, or history of congestive heart failure, unstable angina, uncontrolled hypertension, or clinically significant ventricular arrhythmias at screening;
   2. Myocardial infarction within 6 months prior to screening;
   3. QTcF interval on electrocardiogram (ECG) at screening > 450 msec for males or > 460 for females;
4. Known hepatic impairment including cirrhosis, known renal impairment including renal insufficiency or glomerulonephritis and severe cerebral or peripheral vascular disease;
5. Any gastrointestinal disorder with diarrhea as a major symptom, such as Crohn's, or pre- existing chronic diarrhea CTCAE Grade ≥ 2 of any etiology. Included are malabsorption disorders or surgical procedures that in the opinion of the investigator may affect absorption of study drug;
6. Known active fungal, bacterial, and/or known viral infection including human immunodeficiency (HIV) or viral (A, B, or C) hepatitis (screening is not required).;
7. Major surgery within 21 days before Study Day 1;

8. Have taken any of the following drugs within 7 days prior to Study Day 1:

   1. Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil);
   2. Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin), OCT1 transporter (e.g., metformin), OAT1 transporter (e.g., captopril, furosemide, methotrexate), and OATP1B3 transporter (e.g., atorvastatin, rosuvastatin, valsartan);
9. Known or suspected active drug or alcohol abuse;