Safety, Tolerability and Pharmacokinetics Characteristics of Recombinant Oncolytic Vaccinia Virus Injection T601 as a Single Drug or in Combination With Oral Flucytosine (5-FC), in Patients With Advanced Malignant Solid Tumors

NCT04226066 | Unknown Phase 1

• 1 other identifier: T60101
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 2

Brief Summary

This open, dose-escalation and extended PhI/IIa clinical trial aims to evaluate the safety, tolerability of T601 as a single-agent as well as combined with prodrug 5-FC to treat patients with advanced malignant solid tumors and to explore the pharmacokinetic characteristics of T601, 5-FC, 5-FU, FBAL, which includes PhI study of dose-escalation study and Ph IIa study of extending study.

Conditions

Advanced Malignant Solid Tumors

Keywords

Advanced Malignant Solid Tumors

Outcome Measures

Primary Outcomes (10)

• AEs (adverse events)

  According to NCI CTCAE 5.0., evaluate the AEs and the frequency and severity of adverse events.

  Throughout the whole clinical trial, around 2 years.

• Assessment of ORR (objective response rate)

  According to RECIST v1.1, to assess the ORR of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC

  For Part 2, ORR is measured on Day28 for cycle 1, and after cycle 1, ORR is measured when every 2 cycles finished (for Part 2, each cycle is 28 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of ORR (objective response rate)

  According to RECIST v1.1, to assess the ORR of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC

  For Part 3, ORR is measured at the end of each cycle (for Part 3, each cycle is 46 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of ORR (objective response rate)

  According to RECIST v1.1, to assess the ORR of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC

  For Part 4, ORR is measured at the end of each cycle (for Part 4, each cycle is 46 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of DCR (disease control rate)

  According to RECIST v1.1, to assess the DCR of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC.

  For Part 2, DCR is measured on Day28 for cycle 1, and after cycle 1, DCR is measured when every 2 cycles finished (for Part 2, each cycle is 28 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of DCR (disease control rate)

  According to RECIST v1.1, to assess the DCR of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC.

  For Part 3, DCR is measured at the end of each cycle (for Part 3, each cycle is 46 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of DCR (disease control rate)

  According to RECIST v1.1, to assess the DCR of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC.

  For Part 4, DCR is measured at the end of each cycle (for Part 4, each cycle is 46 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of PFS (progression free survival)

  According to RECIST v1.1, to assess the PFS of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC.

  For Part 2, PFS is measured on Day28 for cycle 1, and after cycle 1, PFS is measured when every 2 cycles finished (for Part 2, each cycle is 28 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of PFS (progression free survival)

  According to RECIST v1.1, to assess the PFS of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC.

  For Part 3, PFS is measured at the end of each cycle (for Part 3, each cycle is 46 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of PFS (progression free survival)

  According to RECIST v1.1, to assess the PFS of the patients, and to evaluate the efficacy of T601 or T601 in combination with 5-FC.

  For Part 4, PFS is measured at the end of each cycle (for Part 4, each cycle is 46 days), until the date of disease progression or death, whichever came first, assessed up to 2 years.

Secondary Outcomes (8)

• Quantification of viral genome in patients' blood samples by Quantitative Polymerase Chain Reaction.

  For Part 1, blood samples are collected on Day1, Day4, Day14, Day21 of cycle 1; Day2, Day21 of cycle 2 (for Part 1, each cycle is 21 days).

• Quantification of viral genome in patients' blood samples by Quantitative Polymerase Chain Reaction.

  For Part 2, blood samples are collected on Day4, Day14, Day28 of cycle 1.

• Quantification of viral genome in patients' blood samples by Quantitative Polymerase Chain Reaction.

  For Part 3, blood samples are collected on Day8, Day15, Day32, Day46 of cycle 1.

• Determination of 5-FC, 5-FU and FBAL concentration in plasma by updated LC/MS/MS method

  For Part 2, blood samples are collected on Day7, Day14, Day18 of cycle 1.

• Determination of 5-FC, 5-FU and FBAL concentration in plasma by updated LC/MS/MS method

  For Part 3, blood samples are collected on Day19, Day20 of cycle 1.

Study Arms (1)

T601/T601+5-FC

EXPERIMENTAL

Part 1: Dose-escalation study of T601 single-dose; Part 2: Dose-escalation study of T601 single-dose combined with 5-FC; Part 3: Dose-escalation study of T601 multiple-dose combined with 5-FC; Part 4: Extended study of T601 multiple-dose combined with 5-FC.

Biological: T601; Combination Product: T601+5-FC

Interventions

T601 BIOLOGICAL

Part1: T601 is injected once (Day1). Dose range: 1E+7, 3E+7, 1E+8, 3E+8, 1E+9pfu.Trial cycle: Day1-21. For part1, 3+3 dose-escalation. After all patients of one dosage finished DLT evaluation, investigator judged that patients can benefit from treatment and no intolerable toxicity occurred, patients could receive maintenance treatment, and treatment plan is same as Cycle 1.

T601/T601+5-FC

T601+5-FC COMBINATION_PRODUCT

Part2: T601 is injected once (Day1). Dose range: MTD-2, MTD-1 and MTD of Part1. 5-FC is taken on Day5-18 for 14 consecutive days. Trial cycle: Day1-28. Part3: T601 is injected 3 times (Day1, 8, 15). Dose range: MTD-1 and MTD, or MTD-2 and MTD-1 of Part2. 5-FC is taken on Day5-7, Day12-14 and Day19-32. Trial cycle: Day1-46. Part4: Protocol revised based on results of Part1-Part3. Preliminary plan: 30 patients with gastric cancer, pancreatic cancer and hepatocellular cancer who have failed standard therapeutic options are enrolled (10 patients for each indication). Treatment plan is same as Part3. For part2 and part3, 3+3 dose-escalation. After all patients of one dosage finished DLT evaluation, investigator judged that patients can benefit from treatment and no intolerable toxicity occurred, patients could receive maintenance treatment, and treatment plan is same as Cycle 1.

T601/T601+5-FC

Eligibility Criteria

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

You may qualify if:

• Male or female, aged ≥18 years and ≤ 75;
• Part1-Part3: histological or cytological confirmed advanced malignant solid tumors patients who have received standard therapeutic options in previous treatment and now there's no standard therapy available; Part4: patients with gastric cancer, pancreatic cancer and hepatocellular carcinoma will be enrolled in Phase IIa Clinical Trial;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Expected survival of at least 3 months;
• Patient presenting with at least one evaluable lesion according to RECIST 1.1 in Part1-Part3; patient presenting with at least one measurable lesion according to RECIST 1.1 in Part4;
• Adequate blood system function, liver function and kidney function:
• ANC≥1.5×109/L，PLT≥80×109/L，Hb≥90 g/L;
• TBIL≤1.5×ULN，ALT≤3×ULN，AST≤3×ULN (Patients with liver metastasis or liver cancer ALT≤5×ULN，AST≤5×ULN);
• Cr≤1.5×ULN, creatinine clearance\>50mL/min (calculate according to Cockcroft-Gault Formula);
• APTT≤1.5×ULN，PT≤1.5×ULN，INR≤1.5×ULN.
• Fertile eligible patients (male and female) must agree to use highly effective method of contraception (i.e. hormone or barrier method or abstinence) during clinical trial and for a minimum of 12 weeks after the last administration of T601; negative blood pregnancy test for women of childbearing potential (WOCBP) within 7 days before enrollment ;
• Give informed consent to the study prior to the test and voluntarily sign a written informed consent.

You may not qualify if:

• Received chemotherapy, radiation, biotherapy, endocrine therapy, immunotherapy and other anti-tumor treatments within 4 weeks prior to T601 treatment initiation, except for the following items:
• Received nitrosourea or mitomycin C within 6 weeks before T601 treatment initiation; Orally taken fluorouracil and small-molecule targeted drugs within 2 weeks before T601 treatment initiation or within 5 half-lives of the above drugs (subject to whichever is longer); Received the Chinese medicines with anti-tumor indications within 2 weeks before T601 treatment initiation;
• Prior participation in another clinical study involving an IMP with last intake within 4 weeks prior to T601 treatment initiation;
• Received major organ surgery (excluding needle biopsy) or severe trauma within 4 weeks prior to T601 treatment initiation;
• The adverse reactions of previous anti-tumor therapy have not yet returned to CTCAE 5.0 ≤1 (except the toxicity that the investigator judged as no safety risk, such as hair loss);
• Uncontrolled bacterial, viral or fungal infections requiring systematic treatment;
• History of immunodeficiency, including positive HIV antibody test;
• Active chronic hepatitis B (HBV-DNA higher than the lower limit of detection), hepatitis C antibody positive;
• Patients who are unable to swallow oral drugs;
• History of serious cardiovascular and cerebrovascular diseases:
• Ventricular arrhythmias requiring clinical intervention;
• Acute coronary syndrome, congestive heart failure, stroke or other class III or above cardiovascular events within 6 months;
• New York Heart Association (NYHA) cardiac function grade ≥II or Left Ventricular Ejection Fraction (LVEF) \<50%;
• Hypertension uncontrolled by standard treatment;
• Skin diseases that need systematic treatment;

Sponsors & Collaborators

• Tasly Tianjin Biopharmaceutical Co., Ltd.: lead

Study Sites (2)

The First Hospital of China Medical University

Shenyang, Liaoning, China

NOT YET RECRUITING

START-SEH New Drug Phase I Clinical Trial Center

Shanghai, China

RECRUITING

Central Study Contacts

Xiaomin WANG, master

CONTACT

+86 22 8634 2163; tsl-wangxiaomin@tasly.com

Study Design

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

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: January 13, 2020
• Study Start: November 20, 2019
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2022
• Last Updated: December 7, 2020

Record last verified: 2020-12

Locations

CN (2)