Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/ Refractory Small Cell Lung Cancer

Fenretinide has been shown to be a relatively safe and effective anticancer therapy; however, low fenretinide bioavailability and dose limiting toxicities due to excipients used in previous formulations has impeded its therapeutic utility. The product formulation in the current study (ST-001) is a phospholipid suspension of nanoparticle sized fenretinide. The current study is a Phase 1 trial in in relapsed/refractory small cell lung cancer to determine the clinical activity, safety profile, and pharmacology of ST-001.

Inclusion criteria

• Small cell lung cancer (SCLC).
• Patients must all have at least one measurable disease site using RECIST version 1.1 criteria.
• Patients must have relapsed or refractory disease to prior treatment with platinum-based chemotherapy ± immunotherapy. There is no limit on the number of prior systemic treatment regimens.
• Relapsed/refractory disease of any stage if incurable in nature, is eligible for enrollment.
• Minimum of 3 weeks or 5 half-lives, whichever is shorter must have elapsed since last systemic treatment. A 1-week washout is required for palliative radiation treatment and 2-week washout is required for whole brain radiation treatment. Patients must have recovered from all clinically significant toxicity of last treatment and cleared the pharmacological agent(s) used previously.
• ECOG performance status 0-1 (Karnofsky ≥60%).
• Life expectancy greater than 6 months.
• Patients must have normal organ and marrow function.
• Triglyceride blood level (fasting) <300mg/dL at time of enrollment (normal: <150mg/dL; borderline high = 150-199mg/dL; high = 200-499mg/dL; very high = 500mg/dL or higher).
• Women of non-child bearing potential, that is women who have been menopausal or surgically sterile for more than 1 year, are eligible for enrolment in the study.
• Informed consent of the patient or a legal authorized representative (LAR) must be obtained prior to any study related procedures.

Exclusion criteria

• Mixed SCLC/NSCLC tumors are not eligible. Pregnant or breastfeeding women cannot take part in this study. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients who are receiving any other investigational agents. SCLC patients with history of CNS metastasis may be included if CNS disease is asymptomatic and controlled without progression at least 4 weeks after treatment with radiotherapy, and patient is either no longer taking corticosteroids or on a stable dose of corticosteroids.
• History of allergic reactions or sensitivity to retinoids or to any excipients of ST-001.
• Patients who require concurrent treatment with drugs that are strong CYP3A inducers are excluded from the trial.
• Patients who require concurrent treatment with drugs that are strong to moderate CYP3A inhibitors are excluded from the trial.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NY heart classification III/IV), unstable angina pectoris, cardiac arrhythmia, QTc interval >450 milliseconds for men and >460 milliseconds for women on baseline triplicate ECG, or psychiatric illness/social situations that would limit compliance with study requirements.
• HIV-positive patients on combination antiretroviral therapy are ineligible. Patients with any active hepatitis infections. Presence of nyctalopia (night blindness), or hemeralopia (defective vision in a bright light, 'day blindness') at enrollment, or any other retinal, ophthalmological condition (e.g.: retinitis pigmentosa, choroidoretinitis and xerophthalmia), and glaucoma.
• History of solid tumor malignancy other than the diseases under study, diagnosed within the last three (3) years of study enrollment, excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment).