Clinical trial NCT04481607: A Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3454 Tablets
Official title: A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3454 Tablets
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor or Hematologic Tumor
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-07-22
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a open-label, multicenter, phase I study to evaluate tolerance and pharmacokinetics of TQB3454 tablets in subjects with advanced solid tumor or hematologic tumor.


Eligibility criteria: Inclusion Criteria:

- 1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Life expectancy ≥12 weeks.

2. Advanced solid tumors or hematological malignancy. 3. Adequate laboratory indicators. 4. No pregnant or breastfeeding women, and a negative pregnancy test. 5. Understood and Signed an informed consent form.

Exclusion Criteria:

* 1. Has central nervous system metastasis or system leukemia. 2.Previous anti-tumor treatment:

  1. Has received IDH1 mutation inhibitor.
  2. Has received systemic anti-tumor therapy or radiotherapy within 14 days before the first dose.
  3. Has received oral targeted drugs, less than 5 drug half-lives from first dose.
  4. The related toxicity of previous anti-tumor therapy has not recovered to CTCAE ≤ grade 2, except for hair loss.

     3.Complicated disease and medical history:

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  1. Active hepatitis B or hepatitis C.
  2. Abnormal kidney.
  3. Abnormal cardiovascular and cerebrovascular.
  4. Abnormal gastrointestinal.
  5. Has medical history of immunodeficiency.
  6. Has bleeding (hemoptysis), coagulopathy, or been using warfarin, aspirin, and other antiplatelet agglutination drugs.
  7. Has uncontrollable systemic bacterial, fungal or viral active infections.
  8. Has medical history of idiopathic pulmonary fibrosis,or tissue pneumonia.
  9. Has allergic constitution or previous severe allergy; or known allergy to ingredients of study drug.
  10. Has neurological or mental disorders.
  11. Has a history of drug abuse or drug addict.
  12. Has received major surgery, open biopsy, or obvious traumatic injury within 4 weeks before the first dose.
  13. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

      4. Has participated in other clinical trials within 30 days before participating in this trial.

      5. Female patients during pregnancy or lactation. 6. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

      7. criteria for solid tumors:

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  1. Has any signs of bleeding constitution.
  2. Has any CTCAE ≥ grade 3 bleeding or bleeding event,within 4 weeks before the first dose.
  3. Has unhealed wounds, fractures, active ulcers of the stomach and duodenum, ulcerative colitis and other digestive tract diseases.
  4. Imaging (CT or MRI) shows that the tumor has invaded the circumference of important blood vessels.
  5. Has uncontrollable pleural effusion, pericardial effusion or ascites that still need repeated drainage.

criteria for blood tumor:

a) Has severe life-threatening leukemia complications.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Baseline up to 28 days
Secondary outcomes:
measure: Cmax
timeFrame: Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
measure: Tmax
timeFrame: Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
measure: AUC0-t
timeFrame: Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
measure: Objective response rate (ORR)
timeFrame: up to 60 weeks
measure: Progression-free survival (PFS)
timeFrame: Up to 60 weeks
measure: 2-hydroxyglutaric acid
timeFrame: Hour 0(pre-dose) on single dose; Hour 0(pre-dose) of day1, day8, day15, day28 on multiple dose of first cycle; hour 0(pre-dose) of day15, day28 of second and third cycle; hour 0(pre-dose) of day28 of fourth to eighth cycle.Each cycle is 28 days.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Xuzhou
country: China
facility: The Affiliated Hosptial of Xuzhou Medical University
state: Jiangsu
city: Tianjin
country: China
facility: Tianjing Medical University Cancer Institute&Hospital
state: Tianjin
city: Tianjin
country: China
facility: Hematology Hospital of Chinese Academy of Medical Sciences
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hosptial Zhejiang University School of Medical
state: Zhejiang
Study officials:
References: