The Phase I/Phase II Clinical Study of VC004 in Patients With Localized Advanced/Metastatic Solid Tumors

NCT04614740 | Unknown Phase 1

• 1 other identifier: VC004-101
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 21

Brief Summary

Dose-escalation study will be conducted in patients with locally advanced/metastatic solid tumors who have failed standard treatment, or cannot tolerate standard treatment, or have no recommended standard treatment, or do not apply standard treatment, to evaluate the safety, PK, tolerability and effectiveness of VC004. According to the efficacy, safety and PK of dose-escalation study , the investigator and the sponsor jointly determine the dose for dose extension, and evaluate the anti-tumor effect of VC004 on NTRK fusion-positive subjects, and provide more information for RP2D. According to the tolerability and pharmacokinetic results of dose-escalation study , an appropriate dose or MTD will be selected, namely RP2D, to further assess anti-tumor efficacy and safety in patients with NTRK fusion-positive locally advanced/metastatic solid tumors . ORR will be chosen as the main efficacy indicator to evaluate the anti-tumor efficacy and safety of VC004 .

Conditions

Locally Advanced Solid Tumor; Metastatic Solid Tumor

Keywords

Safety, Tolerability, Pharmacokinetic, Effectiveness

Outcome Measures

Primary Outcomes (4)

• Safety&Tolerability

  Adverse events (CTCAE5.0)and/or laboratory testsand/or electrocardiogramand/or echocardiogramand/or vital signsand/or physical examination

  4 years

• Phase II recommended dose(RP2D)

  According to the tolerability and pharmacokinetic results of different dose groups completed during the dose escalation phase, an appropriate dose or MTD is selected as RP2D

  1.5 years

• Maximum tolerated dose(MTD)(If any)

  If ≥2 cases of DLT are observed at a certain dose (up to 6 subjects), the dose will be considered an intolerable dose, and the previous dose group will be regarded as MTD

  1.5 years

• Objective response rate(ORR)

  The proportion of subjects whose best overall response is CR or PR in the study assessed by IRC/investigator according to RECIST v1.1 or RANO

  4 years

Secondary Outcomes (8)

• Maximum Observed Plasma Concentration (Cmax)

  0 min ，15 min，30 min，1 hour (h)，2 h，3 h，4 h，6 h，8 h，12 h，24 h，48 h

• Peak time(Tmax)

  0 min ，15 min，30 min，1 hour (h)，2 h，3 h，4 h，6 h，8 h，12 h，24 h，48 h

• half-time（t1/2）

  0 min ，15 min，30 min，1 hour (h)，2 h，3 h，4 h，6 h，8 h，12 h，24 h，48 h

• Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC）

  0 min ，15 min，30 min，1 hour (h)，2 h，3 h，4 h，6 h，8 h，12 h，24 h，48 h

• Apparent volume of distribution(Vz/F)

  0 min ，15 min，30 min，1 hour (h)，2 h，3 h，4 h，6 h，8 h，12 h，24 h，48 h

Study Arms (1)

VC004

EXPERIMENTAL

1\. Dose escalation stage: subjects in the 50 mg, 100 mg, 200 mg, and 300 mg dose groups took a single oral dose on the first day; starting from the fourth day, each group of subjects took the corresponding dose twice a day. 2. Dose expansion stage: subjects in the 100mg and 200mg dose groups took the corresponding dose twice a day on an empty stomach; 3. Phase II clinical trial stage: oral administration twice a day before meals, and the dosage is to be determined.

Drug: VC004

Interventions

VC004 DRUG

25 mg capsules,50 mg capsules,100 mg capsules.

VC004

Eligibility Criteria

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

You may qualify if:

• All subjects or legal representatives are willing and able to sign ICF approved by the ethics committee before starting any screening procedures；
• Male or female, age ≥18 years old
• Patients with locally advanced or metastatic solid tumors diagnosed by histology or cytology, or currently have no standard treatment, have failed the standard treatment, or are intolerant to the standard treatment or are not suitable for the standard treatment at this stage。 The first part of the dose escalation stage: locally advanced or metastatic solid tumors, including but not limited to salivary gland cancer, thyroid cancer, soft tissue sarcoma, liposarcoma, etc.
• Subject's baseline lesion requirements: According to the definition of RECIST v1.1 or RANO, the subject must have at least one measurable lesion (applicable to NTRK fusion-positive locally advanced or metastatic solid tumors)。
• Subjects with primary central nervous system (CNS) tumors must meet the following criteria (only the first part of the dose expansion phase and the second part are applicable)
• According to the guidelines or CNS tumor type, have received treatment including radiotherapy and/or chemotherapy, and the interval between radiotherapy and the first treatment with study drug is at least 12 weeks.
• According to the definition of RANO, there is at least one measurable lesion in magnetic resonance imaging (MRI), which can be visualized on ≥2 axial films with a thickness of 5 mm, and the longitudinal diameters perpendicular to each other are\> 10 mm.
• The imaging examination was performed within 28 days before enrollment. If you receive glucocorticoid treatment, a stable dose of glucocorticoid is required at least 5 days before imaging evaluation.
• The Eastern Cooperative Oncology Group (ECOG) score is ≤2 points (0-1 points are required for the dose-escalation stage)
• The estimated survival time is ≥12 weeks.
• The subject must have appropriate organ and hematological functions (have not received blood transfusion, EPO, G-CSF or other medical supportive treatment within 14 days before the administration of the study drug)。
• Premenopausal women who are likely to have children must have a pregnancy test within 7 days before starting treatment. The pregnancy test must be negative and must be non-lactating; Infertile women may not undergo pregnancy tests and contraception, but they must meet the following requirements: age 50 years or older, not using hormone therapy and menopause for at least 12 months, or have undergone sterilization. All enrolled patients (whether male or female) should take adequate contraceptive measures throughout the treatment period and 180 days after the end of treatment.

You may not qualify if:

• Patients have previously received any of the following treatments:
• Patients have used any cytotoxic chemotherapeutic agents, targeted therapies, immunotherapies, or other anti-cancer drugs in the previous regimen within 4 weeks before the first administration ( e.g.Nitrosourea or mitomycin C for 6 weeks prior to first use of study drug, Oral fluorouracil and small-molecule targeted drugs are administered 2 weeks prior to the first use of the study drug or within 5 half-lives of the drug, whichever is longer.).
• The time from receiving other experimental drugs or analogues to the first dose does not exceed the drug's 5 half-life or 14 days (whichever is longer).
• Patients have used chinese herbal medicines and chinese herbal preparations with antitumor as an indication, chinese herbal medicines and chinese herbal preparations with tumor adjuvant therapeutic effect within 14 days before the first administration.
• Patients have undergone major surgery within 4 weeks prior to the first dose or are expected to undergo major surgery during the trial (excluding vascular access establishment procedures, biopsy procedures)
• Adverse reactions caused by previous treatment have not recovered to ≤1 grade (the dose-escalation stage does not include ≤2 grade hair loss, and the dose expansion stage and phase II clinical trials are comprehensively evaluated by the investigator).
• Primary central nervous system malignancy (only the first part of the dose escalation phase).
• Patients are known to have symptomatic or untreated brain metastases or other central nervous system metastases.CNS lesions that remain stable or show improvement after treatment with complete resection and/or radiation therapy are excluded, but require no glucocorticoids to control neurological symptoms within 14 days prior to entry into this study.
• There is any clinical basis suggesting a severe or uncontrolled systemic disease for which the investigator believes the patient is unsuitable for trial participation or which would affect the patient's compliance with the study protocol, such as stable or decompensated respiratory disease, cerebrovascular disease, liver disease, renal disease, uncontrolled diabetes, aortic dissection, aortic aneurysm, active bleeding-prone body, or those requiring systemic anti-infective therapy.
• Any clinically serious gastrointestinal abnormality that may affect the ingestion, transit, or absorption of study drugs.
• Patients have clinically significant cardiovascular diseases, including：
• Left ventricular ejection fraction (LVEF) ≤ 50% by echocardiography during the screening period
• Heart Failure, New York Heart Association (NYHA) grade III and above
• Poorly controlled hypertension (BP ≥ 150/100 mmHg despite use of optimal therapy)
• Past or current cardiomyopathy

Sponsors & Collaborators

• Jiangsu vcare pharmaceutical technology co., LTD: lead

Study Sites (21)

Anhui Provincial Cancer Hospital

Hefei, Anhui, 230001, China

NOT YET RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

NOT YET RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350001, China

NOT YET RECRUITING

Guangxi Medical University Affiliated Tumor Hospital

Nanning, Guangxi, 530021, China

NOT YET RECRUITING

Hainan Cancer Hospital

Haikou, Hainan, 570312, China

NOT YET RECRUITING

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

NOT YET RECRUITING

Harbin Medical Univercity Cancer Hospital

Harbin, Heilongjiang, 150081, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

RECRUITING

Jiangsu Province Hospital of Chinese Medicine

Nanjing, Jiangsu, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

NOT YET RECRUITING

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality, 200072, China

NOT YET RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, Shanxi, 030013, China

NOT YET RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650106, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

NOT YET RECRUITING

Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, China

RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, China

RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, China

RECRUITING

Tianjin Cancer Hospital

Tianjin, China

RECRUITING

The First Affiliated Hospital of Xinjiang Medical University

Ürümqi, China

RECRUITING

Hubei Cancer Hospital

Wuhan, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• yuankai shi

  Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

xiaojuan lai

CONTACT

15358160458; lai_xiaojuan@vcarepharmatech.com

Study Design

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

Model Details: Single arm clinical study

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: November 4, 2020
• Study Start: November 20, 2020
• Primary Completion: January 31, 2024
• Study Completion: June 30, 2024
• Last Updated: December 13, 2022

Record last verified: 2022-10

Locations

CN (21)