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

Single-center, Dose Escalation, Open Phase I Clinical Study of Oral TG02 Capsule in the Treatment of Recurrent / Progressive High-grade Glioma Patients With Failed TMZ Treatment

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.

Study Overview

• Status: Unknown
• Conditions: High-grade Gliomas
• Intervention / Treatment: Drug: TG02 capsules oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d

Detailed Description

Using the traditional 3 +3 design, 150 mg as the initial dose and 50 mg as the increasing interval of up to 250 mg, and oral administration on the 1st, 4th, 8th, 11th, 15th, 18th, 22nd and 25th day of each 28-day cycle. Phase I clinical study to evaluate the tolerance and pharmacokinetic parameters of oral TG02 capsules.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhongping Chen, doctor; Phone Number: +8613500002457; Email: chenzhp@sysucc.org.cn
• Study Contact Backup: Name: Zhengzheng Guo, doctor; Phone Number: +8613580332120; Email: guochch@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Zhongping Chen, doctor; Phone Number: +8613500002457; Email: chenzhp@sysucc.org.cn
      • Contact: Zhengzheng Guo, doctor; Phone Number: +8613580332120; Email: guochch@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Age: 18 ~ 75 years old, both men and women.
2. Histologically proven glioblastoma or anaplastic astrocytoma that has failed from temozolomide treatment in the past.
3. According to RANO criteria, patients with clinically evaluated recurrence or progression with clearly measurable lesions.
4. 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. .
5. The first day of treatment was ≥ 2 weeks from the second surgery of recurrence, and the incision is healed in grade A.
6. ECOG 0 - 2 points, can swallow the drug and maintain oral administration.
7. The expected survival time was more than 3 months.
8. The hematopoietic function of bone marrow was adequate: ANC≥1.5×109/L，PLT≥100×109/L，Hb≥90 g/L；.
9. Patients who had previously undergone surgical resection were able to provide no less than 15 tumor tissue sections and pathological reports for the study.

Exclusion criteria

1. 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).
2. Bevacizumab was treated within 6 weeks before the start of the study.
3. Previous treatment with carmostine sustained-release implants or intracerebral implantation of radiotherapy.
4. A patient with a major seizure that cannot be effectively controlled by drugs.
5. MRI examinations cannot be performed (e.g. pacemakers, undesirable metal dentures, etc.).
6. 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;
7. 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).
8. 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.
9. Active peptic ulcer or inflammatory bowel disease.
10. Active hepatitis, or HIV, Treponema pallidum infection.
11. Pregnant or breastfeeding.
12. 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.
13. Currently participating in another clinical trial or within 30 days of the last administration of the trial drug.
14. The subjects had conditions that affected their provision of written informed consent and / or compliance with the research process.
15. There were cases in which any other investigator did not consider it appropriate to join the group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 150 mg, BIW in every 28d; 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; TG02 capsules150mg oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d; TG02 capsules 200mg oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d; TG02 capsules 250mg oral administration, BIW in every 28d
Experimental: 200 mg, BIW in every 28d; 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; TG02 capsules150mg oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d; TG02 capsules 200mg oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d; TG02 capsules 250mg oral administration, BIW in every 28d
Experimental: 250 mg, BIW in every 28d; 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; TG02 capsules150mg oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d; TG02 capsules 200mg oral administration, BIW in every 28d; Drug: TG02 capsules oral administration, BIW in every 28d; TG02 capsules 250mg oral administration, BIW in every 28d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal tolerable dose(MTD)	DLT occurs in less than 1/6 subjects, this lower dose is defined as MTD.	28 days after first dose
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate（ORR）	proportion of patients whose best overall response during their participation in the study is either CR or PR. The best overall response is the best response recorded from first dose until disease progression.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
c-myc expression in tumor tissue	the relationship between c-myc expression in tumor tissue with the tumor response	12 months

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2019
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): October 31, 2020

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 3, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): April 14, 2020
• Last Update Submitted That Met QC Criteria: April 13, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: NTL-LEES-2018-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No