Phase I Open-Label Dose-Escalating Study to Determine the Safety, Tolerability, Maximum Tolerated Dose, and Pharmacokinetics of SC-43 Oral Solution in Subjects With Refractory Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- SC-43 Oral Solution
- Conditions
- Refractory Solid Tumor
- Sponsor
- SupremeCure Pharma Inc.
- Primary Endpoint
- maximum tolerated dose (MTD)
- Status
- Withdrawn
- Last Updated
- 5 years ago
Overview
Brief Summary
This phase I study will be conducted in an open-label, conventional 3+3 dose escalation design manner (for the first 28 days of dosing) followed by an extension period for subjects responsive to the study drug to continue dosing up to 52 weeks. This study is intended to assess the safety and efficacy of the investigational product (IP), SC-43 Oral Solution, in subjects with refractory solid tumors. Subjects who have diseases progressing unresponsive to the previous treatments or who have no standard treatments for their current diseases will be enrolled in this study once the eligibility is confirmed.
During the first 28 days, the study will be done in the conventional 3+3 design to determine the maximum tolerated dose (MTD) of SC-43 Oral Solution. The dose will be increased in a step-wise fashion from the initial dose of 100 mg/day to the dose of 200, 400, 600, 900, and 1200 mg/day. The pharmacokinetics (PK) of SC-43 will also be measured in this period.
The dose of SC-43 Oral Solution will be escalated to the subsequent cohorts when there is no dose-limiting toxicity (DLT) in 3 subjects or only one DLT in 6 subjects of the previous cohort, and it is recommended by Data and Safety Monitoring Board (DSMB). The safety results will be reviewed by DSMB after the last subject in the each cohort has finished the Visit 6 (Day 29), and DSMB will determine if it is safe to proceed to the next dose cohort.
Subjects who have finished the 28-day dose escalation period and with complete response (CR), partial response (PR), or stable disease (SD) will be eligible to enter the extension period and continue SC-43 Oral Solution therapy up to 52 weeks or until occurrence of unacceptable toxicity, withdrawn consent, disease progression, not receiving medical benefit as considered by investigators, loss of follow-up, or death, whichever comes first. For ethical and safety concerns, the dosage used in this extension period can be adjusted and different from the original dosage assignment. The actual dose of SC-43 Oral Solution, which must be confirmed safe, administered during this extension period will be at the investigator's discretion.
Detailed Description
SC-43, has been shown to enhance the activity of Src homology region 2 domain-containing phosphatase-1 (SHP-1), leading suppression of STAT3 phosphorylation and tumor growth inhibition. SC-43 enhances SHP-1 activity by impairing the association between the N-SH2 domain and the PTP domain of SHP-1, triggering a conformational change of SHP-1 and relieving its autoinhibition. SC-43 treatment leads to cancer cell death in multiple cancer cell lines. SC-43 also exhibits anti-cancer activity in a variety of nonclinical xenograft tumor models.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Either gender, aged 20 to 75 years old (inclusive; the legal age of consent majority is 20 years old in Taiwan)
- •Life expectancy ≥ 12 weeks
- •With histologically or cytologically confirmed solid tumor(s) that is refractory to standard treatments, or for which a standard therapy is not available or is no longer effective
- •With at least one measurable target lesion as measured by MRI or CT according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria
- •Subject who has received local therapies (such as surgery, radiation therapy, hepatic arterial embolization, or chemoembolization) is eligible. Local therapies must be completed at least 4 weeks prior to the baseline scan. However, the local therapy-treated tumor should be excluded for evaluation.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≦2
- •If female subject or female spouse/partner of male subject is of childbearing potential, she/he must agree to use highly effective contraceptives from signing informed consent to 28 days after the last dose of study drug administration.
- •At least two forms of birth control must be adopted and one of which must be a barrier method. Acceptable forms include:
- •Established use of oral, injected or implanted hormonal methods of contraception
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Exclusion Criteria
- •With primary central nervous system (CNS) malignancies or clinically active CNS metastases
- •The target solid tumor is lymphoma
- •Any of the following hematologic abnormalities:
- •Hemoglobin \< 8.0 g/dL
- •Absolute neutrophil count (ANC) \< 1,000/μL
- •Platelets \< 80,000 /μL
- •Any of the following serum chemistry abnormalities:
- •Total bilirubin \> 1.5 × ULN
- •AST or ALT \> 2.5 × ULN (\> 5 × ULN in patients with HCC)
- •γ-GT \> 2.5 × ULN (\> 5 × ULN in patients with HCC)
Arms & Interventions
SC-43 100 mg/day
SC-43 Oral Solution (100 mg/ml), 1 ml by mouth, q.d. for 28 days
Intervention: SC-43 Oral Solution
SC-43 200 mg/day
SC-43 Oral Solution (100 mg/ml), 2 ml by mouth, q.d. for 28 days
Intervention: SC-43 Oral Solution
SC-43 400 mg/day
SC-43 Oral Solution (100 mg/ml), 4 ml by mouth, q.d. for 28 days
Intervention: SC-43 Oral Solution
SC-43 600 mg/day
SC-43 Oral Solution (100 mg/ml), 6 ml by mouth, q.d. for 28 days
Intervention: SC-43 Oral Solution
SC-43 900 mg/day
SC-43 Oral Solution (100 mg/ml), 9 ml by mouth, q.d. for 28 days
Intervention: SC-43 Oral Solution
SC-43 1200 mg/day
SC-43 Oral Solution (100 mg/ml), 12 ml by mouth, q.d. for 28 days
Intervention: SC-43 Oral Solution
Outcomes
Primary Outcomes
maximum tolerated dose (MTD)
Time Frame: 28 days
The highest dose level at which \< 2 of 6 subjects experienced a dose limiting toxicity during the first 28 days of the treatment period.
Secondary Outcomes
- Disease control rate (DCR) according to RECIST criteria version 1.1(28 days)
- The maximum plasma concentration (Cmax)(28 days)
- Number of patients with treatment-related adverse events (AEs) based on NCI-CTCAE version 5.0(28 days)
- Objective response rate (ORR) according to RECIST criteria version 1.1(28 days)
- Area under the plasma concentration versus time curve (AUC)(28 days)