Small Cell Lung Cancer
Conditions
Keywords
fenretinide, SCLC, Relapsed/Refractory, Relapsed/Refractory SCLC, R/R SCLC, ST-001, intravenous administration
Brief summary
This study evaluates a fenretinide phospholipid suspension for the treatment of small cell lung cancer (SCLC).
Detailed description
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.
Interventions
DRUGFenretinide
Intravenous administration
Sponsors
SciTech Development, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the progression-free survival (PFS) of patients with relapsed or refractory small-cell lung cancer (SCLC) who are treated with ST-001 after receiving at least one prior systemic therapy. | From enrollment to end of treatment is 3 weeks | Evaluate progression-free survival (PFS) in patients with relapsed or refractory small-cell lung cancer (SCLC) after prior platinum-based chemotherapy ± immunotherapy who are treated with ST-001 (12.5mg/mL) for IV Infusion, using a Simon 2-stage study design with an interim analysis for futility. PFS is defined as the time from start of treatment to disease progression (increase in tumor size, new metastases) or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To describe the toxicity profile of ST-001 in patients with SCLC | From enrollment to end of treatment is 3 weeks | Determine the number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
| To observe and record anti-tumor activity of ST-001 in patients with SCLC | From enrollment to end of treatment is 3 weeks | Preclinical studies with fenretinide suggest potential efficacy against SCLC. Patients will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. Objective Response Rate (ORR) and progression-free survival (PFS) will be used as tumor response endpoints in this study. |
| Objective Response Rate (ORR) | From enrollment to end of treatment is 3 weeks | ORR = (Number of patients with complete or partial response) / (Total number of evaluable patients) x 100. Minimum duration of individual patient participation is 3 weeks (one cycle of therapy) to be evaluable for response. |
| To describe the pharmacokinetics of fenretinide when ST-001 is administered by daily infusion for 5 consecutive days every 3 weeks. | From enrollment to end of treatment is 3 weeks | The endpoint for the pharmacokinetic studies is to assess fenretinide blood plasma levels as a function of administered dose and to determine the following PK parameters: maximum fenretinide concentration (Cmax), time of Cmax (Tmax), volume of distribution (Vd), clearance (CL), elimination and fenretinide half-life (t½). |
| Cmax | From enrollment to end of treatment is 3 weeks | Peak plasma fenretinide concentration (in ng/mL) |
| Tmax | From enrollment to end of treatment is 3 weeks | The time it takes for fenretinide to reach the maximum concentration (Cmax) after drug administration (in hours) |
| Vd | From enrollment to end of treatment is 3 weeks | Volume of distribution; fenretinide's propensity to either remain in the plasma or redistribute to other tissue compartments (in liters) |
| t½ | From enrollment to end of treatment is 3 weeks | Fenretinide elimination and half-life; the time it takes for the amount of a drug's active substance in your body to reduce by half (hours) |
Countries
United States
Contacts
CONTACTLouis M Scarmoutzos, Ph.D.
STUDY_DIRECTORAli Moiin, MD
SciTech Development, Inc.
Outcome results
None listed