Phase I Study of SC-43 Oral Solution in Subjects With Refractory Solid Tumors

NCT03443622 | Withdrawn Phase 1

• 1 other identifier: SC-43-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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extension period and continue SC-43 Oral Solution therapy up to 52 weeks or until occurrence of unacceptable toxicity, withdrawn consent, disease progression, not receiving medical benefit as considered by investigators, loss of follow-up, or death, whichever comes first.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.

Conditions

Refractory Solid Tumor

Keywords

SC-43; refractory solid tumor; Phase I

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  The highest dose level at which \< 2 of 6 subjects experienced a dose limiting toxicity during the first 28 days of the treatment period.

  28 days

Secondary Outcomes (5)

• Objective response rate (ORR) according to RECIST criteria version 1.1

  28 days

• Disease control rate (DCR) according to RECIST criteria version 1.1

  28 days

• The maximum plasma concentration (Cmax)

  28 days

• Area under the plasma concentration versus time curve (AUC)

  28 days

• Number of patients with treatment-related adverse events (AEs) based on NCI-CTCAE version 5.0

  28 days

Study Arms (6)

SC-43 100 mg/day

EXPERIMENTAL

SC-43 Oral Solution (100 mg/ml), 1 ml by mouth, q.d. for 28 days

Drug: SC-43 Oral Solution

SC-43 200 mg/day

EXPERIMENTAL

SC-43 Oral Solution (100 mg/ml), 2 ml by mouth, q.d. for 28 days

Drug: SC-43 Oral Solution

SC-43 400 mg/day

EXPERIMENTAL

SC-43 Oral Solution (100 mg/ml), 4 ml by mouth, q.d. for 28 days

Drug: SC-43 Oral Solution

SC-43 600 mg/day

EXPERIMENTAL

SC-43 Oral Solution (100 mg/ml), 6 ml by mouth, q.d. for 28 days

Drug: SC-43 Oral Solution

SC-43 900 mg/day

EXPERIMENTAL

SC-43 Oral Solution (100 mg/ml), 9 ml by mouth, q.d. for 28 days

Drug: SC-43 Oral Solution

SC-43 1200 mg/day

EXPERIMENTAL

SC-43 Oral Solution (100 mg/ml), 12 ml by mouth, q.d. for 28 days

Drug: SC-43 Oral Solution

Interventions

SC-43 Oral Solution DRUG

SC-43 Oral Solution has drug substance of 1-\[4-chloro-3(trifluoromethyl)phenyl-3-\[3-(4-cyanophenoxy)\] urea, or SC-43. SC-43 inhibits tumor growth through the activation of Src homology region 2 domain-containing phosphatase-1 (SHP-1) and the repression of p-STAT3 signalings. As a result of STAT3 inhibition by SC-43 treatment, decreased cell viability and enhanced apoptosis have been observed in cancer cells. The anti-tumor activity of SC-43 was also investigated in a variety of xenograft tumor models. Administration of SC-43 provides the tumor-bearing animals survival benefits, including the reduction of tumor volume and prolonged lifespan. SC-43 has been proposed to be evaluated as an anticancer therapeutic in in subjects with refractory solid tumors in the phase I trial.

SC-43 100 mg/day; SC-43 1200 mg/day; SC-43 200 mg/day; SC-43 400 mg/day; SC-43 600 mg/day; SC-43 900 mg/day

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Barrier methods of contraception: condom, or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
• Dated and signed informed consent

You may not qualify if:

• 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)
• ALP \> 2.5 × ULN (\> 5 × ULN in patients with HCC)
• Serum albumin \< 2.5 g/dL
• Creatinine \> 1.5 × ULN
• aPTT \>1.5 × ULN
• INR \>1.5 × ULN

Sponsors & Collaborators

• SupremeCure Pharma Inc.: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2018
• First Posted: February 23, 2018
• Study Start: May 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: June 1, 2023
• Last Updated: October 22, 2020

Record last verified: 2020-10