Safety and Tolerability Study for T-1201 Injection 100 mg Kit in Patients With Advanced Solid Tumors

Official title

A Phase I, Open-label, Dose-finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of T-1201 Injection 100 mg Kit in Patients With Advanced Solid Tumors

Overview

The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of T-1201 injection in subjects with advanced solid tumors refractory to standard therapy, or for whom no standard therapy is available. The main questions it aims to answer are: * The Maximum tolerated dose (MTD) of T-1201 on different dosing schedules. * The Recommended Phase 2 dose (RP2D) of T-1201 on different dosing schedules. Researchers will evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of T-1201. Participants will: Received T-1201 either once every 4 (Part A)/2 (Part B)/3 (Part C) weeks, depend on they participate in which parts of study. Visit the clinic once every 2/3 weeks for checkups and tests

Interventions

• Drug T-1201 Injection 100 mg Kit
  T-1201 Injection 100 mg Kit contains lyophilized powder with a sterile aqueous solution formulated for intravenous administration.

Primary outcome measures

• Maximum tolerated dose (MTD) [Time frame: First treatment cycle (i.e., the first 28 days post the first dose)]
• Recommended Phase 2 dose (RP2D) dose (RP2D) [Time frame: First treatment cycle (i.e., the first 28 days post the first dose)]
• Frequency, type, severity and relationship to study drug of adverse events (AEs) [Time frame: At least 2 months]

Secondary outcome measures (9)

• Pharmacokinetic profiles: Cmax of T-1201 and its metabolite(s) [0060 and SN-38] [Time frame: 340 hours]
• Pharmacokinetic profiles: Tmax of T-1201 and its metabolite(s) [0060 and SN-38] [Time frame: 340 hours]
• Pharmacokinetic profiles: MRT of T-1201 and its metabolite(s) [0060 and SN-38] [Time frame: 340 hours]
• Pharmacokinetic profiles: AUC of T-1201 and its metabolite(s) [0060 and SN-38] [Time frame: 340 hours]
• Pharmacokinetic profiles: T1/2 of T-1201 and its metabolite(s) [0060 and SN-38] [Time frame: 340 hours]
• Assess preliminary anti-tumor activity: ORR of T-1201 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [Time frame: At least 56 days]
• Assess preliminary anti-tumor activity: CBR of T-1201 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [Time frame: At least 56 days]
• Assess preliminary anti-tumor activity: DOR of T-1201 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [Time frame: At least 56 days]
• Assess preliminary anti-tumor activity of T-1201 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [Time frame: At least 56 days]

Eligibility criteria

Inclusion criteria

Subjects must meet all of the following criteria to be eligible for enrollment in the study:

• Signed and dated informed consent form.
• Histologically and cytologically confirmed advanced malignancies that are refractory to standard therapy or have no accepted standard therapy.
• Solid tumors that are measurable or evaluable as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Target lesions that have been previously irradiated will not be considered measurable (lesion).
• Female or male, 20 years of age or older.
• ECOG performance status 0 or 1.
• QTcF ≤ 470 ms at screening.

Exclusion criteria

Subjects presenting with any of the following will not be included in the study:

• Clinically significant comorbidity such as unstable angina, congestive heart failure (NYHA Grade III or IV), uncontrolled hypertension (>160/100 mmHg despite optimal medical treatment), chronic obstructive pulmonary disease (COPD) with frequent exacerbations, refractory asthma, inflammatory bowel disease or intestinal obstruction.
• Acute myocardial infarction or cerebrovascular accident (CVA) within 6 months prior the first dose of study drug.
• Central nervous system (CNS) metastasis or seizure disorder due to underlying malignancy except those who have been treated and have stable CNS metastases or are asymptomatic.
• AIDS-defining opportunistic infections within the past 12 months.
• HBV infection (positive HBsAg) except for carrier of inactive HBV as defined by negative HBeAg with normal ALT and HBV DNA < 2,000 IU/mL or HCV infection (positive anti-HCV antibody) except for those with undetectable HCV RNA.
• Inadequate bone marrow reserve, hepatic or renal function as defined by any of the following laboratory values:

• absolute neutrophil count (ANC) < 1500/µL
• platelet count < 100 x 10\^9 /µL
• hemoglobin < 9 g/dL
• total bilirubin > 1.5 x the upper limit of normal (ULN)
• aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN if no hepatic metastases are present; > 5 x ULN if hepatic metastases are present
• Estimated (Cockroft-Gault formula) creatinine clearance (CrCl) < 60 mL/min CrCl = \[(140 - age (year)) x weight (kg)\] / (serum creatinine x 72) (x 0.85 for females)
• Toxicities resulting from prior therapy or surgical procedures not yet resolved to ≤ NCI CTCAE v5.0 Grade 1 with the exception of alopecia, skin hyperpigmentation or hypopigmentation.
• Major surgical procedures (as defined by Investigator) within 4 weeks prior to the first dose of study drug or any ongoing post-operative complications.
• Receiving any (investigational or approved) anti-cancer therapy (including chemotherapy or targeted therapy) within 28 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
• A history of apparent allergic reactions to irinotecan, Tween 80 (dosed with prior treatment with prophylactic drug), and/or ethanol.
• If female, is pregnant or breastfeeding.
• If men or women with childbearing potential, unwilling to use effective contraceptive methods during the study and for at least 3 months (men) or 1 month (women) after the last dose of study drug. Effective contraceptive methods include implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual abstinence, surgical sterilization or a partner who is sterile.
• Receiving live attenuated vaccine within 28 days prior to the first dose of study drug.
• Life expectancy < 3 months
• Other prior or ongoing condition(s) that, in Investigator's opinion, could affect the safety of the subject, compromise the subject's ability to comply with the study requirements or impair the assessment of study results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 2 centers

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City
• National Cheng Kung University Hospital — Tainan

Identifiers

NCT: NCT04866641 · TAI-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗