Phase I Clinical Study of Oral TG02 Capsule in the Treatment of Recurrent / Progressive High-grade Glioma Patients

NCT03904628 | Unknown Phase 1

• 1 other identifier: NTL-LEES-2018-02
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study was to explore the dose-limiting toxicity (DLT) and the maximum tolerable dose (MTD) of oral administration of TG02 capsules twice a week for 4 weeks.

Conditions

High-grade Gliomas

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v5.0.

  28 days after first dose

• Maximal tolerable dose(MTD)

  DLT occurs in less than 1/6 subjects, this lower dose is defined as MTD.

  28 days after first dose

Secondary Outcomes (1)

• Overall response rate（ORR）

  12 months

Other Outcomes (1)

• c-myc expression in tumor tissue

  12 months

Study Arms (3)

150 mg, BIW in every 28d

EXPERIMENTAL

TG02 capsules were given orally at 150 mg on the 1st, 4th, 8th, 11th, 15th, 18th, 22nd and 25th day, every 28 days.

Drug: TG02 capsules oral administration, BIW in every 28d

200 mg, BIW in every 28d

EXPERIMENTAL

TG02 capsules were given orally at 200 mg on the 1st, 4th, 8th, 11th, 15th, 18th, 22nd and 25th day, every 28 days.

Drug: TG02 capsules oral administration, BIW in every 28d

250 mg, BIW in every 28d

EXPERIMENTAL

TG02 capsules were given orally at 250 mg on the 1st, 4th, 8th, 11th, 15th, 18th, 22nd and 25th day, every 28 days.

Drug: TG02 capsules oral administration, BIW in every 28d

Interventions

TG02 capsules oral administration, BIW in every 28d DRUG

TG02 capsules150mg oral administration, BIW in every 28d

150 mg, BIW in every 28d

Eligibility Criteria

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

You may qualify if:

• Age: 18 \~ 75 years old, both men and women.
• Histologically proven glioblastoma or anaplastic astrocytoma that has failed from temozolomide treatment in the past.
• According to RANO criteria, patients with clinically evaluated recurrence or progression with clearly measurable lesions.
• If previous radiotherapy has been performed, it must be completed for a period of more than 3 months, or within 3 months but tumor progression occurs in the original radiation field or has been confirmed by histopathology. .
• The first day of treatment was ≥ 2 weeks from the second surgery of recurrence, and the incision is healed in grade A.
• ECOG 0 - 2 points, can swallow the drug and maintain oral administration.
• The expected survival time was more than 3 months.
• The hematopoietic function of bone marrow was adequate: ANC≥1.5×109/L，PLT≥100×109/L，Hb≥90 g/L；.
• Patients who had previously undergone surgical resection were able to provide no less than 15 tumor tissue sections and pathological reports for the study.

You may not qualify if:

• Other cytotoxic drugs were received within 28 days prior to the start of the study, or adverse reactions from previous systematic treatment have not recovered (except alopecia and pigmentation).
• Bevacizumab was treated within 6 weeks before the start of the study.
• Previous treatment with carmostine sustained-release implants or intracerebral implantation of radiotherapy.
• A patient with a major seizure that cannot be effectively controlled by drugs.
• MRI examinations cannot be performed (e.g. pacemakers, undesirable metal dentures, etc.).
• Patients with severe impairment of liver and kidney function: ALT ≥ 2.5 ULN,AST ≥ 2.5 ULN in patients without liver metastasis; ALT ≥ 5 ULN,AST ≥ 5 ULN in patients with liver metastasis; Or TBIL ≥ 1.5 ULN, or Cr ≥ 1.5 ULN, or creatinine clearance ≤ 60 ml/ min calculated by Cockcroft-Gault formula;
• Unstable or uncontrollable diseases or conditions related to or affecting cardiac function (e.g. unstable angina pectoris, congestive heart failure \[NYHA \> II\], uncontrolled hypertension \[diastolic blood pressure \> 85 mmHg; systolic blood pressure \>145 mmHg\]), arrhythmia or prolonged QTc interval (male \> 450 Ms; female \> 470ms).
• A history of arterial thromboembolism (such as stroke, transient ischemic attack, or myocardial infarction) within 6 months. Bleeding or hypercoagulable coagulation disorder occurred within 6 months prior to the first day of the study.
• Active peptic ulcer or inflammatory bowel disease.
• Active hepatitis, or HIV, Treponema pallidum infection.
• Pregnant or breastfeeding.
• Subjects who were unable to use adequate contraception during the study and for six months after the end of the study were unable to use adequate contraception.
• Currently participating in another clinical trial or within 30 days of the last administration of the trial drug.
• The subjects had conditions that affected their provision of written informed consent and / or compliance with the research process.
• There were cases in which any other investigator did not consider it appropriate to join the group.

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Interventions

14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene; Administration, Oral

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Zhongping Chen, doctor

CONTACT

+8613500002457; chenzhp@sysucc.org.cn

Zhengzheng Guo, doctor

CONTACT

+8613580332120; guochch@sysucc.org.cn

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: April 3, 2019
• First Posted: April 5, 2019
• Study Start: March 22, 2019
• Primary Completion: August 1, 2020
• Study Completion: October 31, 2020
• Last Updated: April 14, 2020

Record last verified: 2020-04

Locations

CN (1)