Clinical Study on the Treatment of Recurrent Glioblastoma With Anlotinib

Recurrent Glioblastoma Clinical Trial

Official title:

Phase II Clinical Trials on Anlotinib for the Treatment of Recurrent Glioblastoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04004975
• Other study ID #: ShandongCHI006
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 25, 2019
• Est. completion date: July 25, 2021

Study information

• Verified date: July 2019
• Source: Shandong Cancer Hospital and Institute
• Contact: Rongjie Tao, Dr.
• Phone: 13969191909
• Email: rongjietao[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor that can inhibit tumor angiogenesis and inhibit tumor cell growth. We performed second-generation gene sequencing on pathological specimens and cerebrospinal fluid of patients with recurrent glioblastoma.If patients have a genetic mutation （VEGFR，Kit，PDGFR，FGFR）and meet other eligibility criteria, they will be treated with antroinib. The initial observation targets were progression-free survival and adverse reactions. The secondary objective was overal survival.

Description:

INCLUSION CRITERIA:

1. Histologically confirmed World Health Organization (WHO) Grade IV glioblastoma.;

2. Radiographic evidence of tumour progression or recurrence;

3. The second-generation gene sequencing on pathological specimens and cerebrospinal fluid show at least one genetic mutation of the four genes (VEGFR，Kit，PDGFR，FGFR);

4. ≥ 18 years of age;

5. Karnofsky performance status (KPS) ≥ 70;

6. Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan.

7. a new baseline scan is required 1.7 Measurable disease as per Response Assessment in Neuro-Oncology (RANO) criteria;

8. Estimated survival of at least 3 months;

9. signed informed consent form;

10. Hgb > 9 gm; absolute neutrophil count (ANC) > 1500/μl; platelets > 100,000; Creatinine < 1.5 times the upper limit of laboratory normal value; Bilirubin < 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) < 3 times the upper limit of laboratory normal value;

EXCLUSION CRITERIA:

Exclusion Criteria:

1. Subjects with newly diagnosed GBM

2. Pregnant women or nursing mothers cannot participate in the study. Women of childbearing age must have a negative pregnancy test within 72 hours prior to study entry. Women of childbearing potential must practice medically approved contraceptive precautions;

3. Abnormal hematological results at inclusion with: Neutrophils < 1,500/mm3; Blood-platelets < 100,000/mm3

4. Severe or chronic renal insufficiency (creatinine clearance ≤ 30 ml/min);

5. Patient unable to follow procedures, visits, examinations described in the study;

6. Any usual formal indication against imaging examinations (important claustrophobia, pacemaker);

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 25, 2021
• Est. primary completion date: July 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed World Health Organization (WHO) Grade IV glioblastoma.;

2. Radiographic evidence of tumour progression or recurrence;

3. The second-generation gene sequencing on pathological specimens and cerebrospinal fluid show at least one genetic mutation of the four genes (VEGFR,Kit,PDGFR,FGFR);

4. = 18 years of age;

5. Karnofsky performance status (KPS) = 70;

6. Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan.

7. a new baseline scan is required 1.7 Measurable disease as per Response Assessment in Neuro-Oncology (RANO) criteria;

8. Estimated survival of at least 3 months;

9. signed informed consent form;

10. Hgb > 9 gm; absolute neutrophil count (ANC) > 1500/µl; platelets > 100,000; Creatinine < 1.5 times the upper limit of laboratory normal value; Bilirubin < 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) < 3 times the upper limit of laboratory normal value;

Exclusion Criteria:

1. Subjects with newly diagnosed GBM

2. Pregnant women or nursing mothers cannot participate in the study. Women of childbearing age must have a negative pregnancy test within 72 hours prior to study entry. Women of childbearing potential must practice medically approved contraceptive precautions;

3. Abnormal hematological results at inclusion with: Neutrophils < 1,500/mm3; Blood-platelets < 100,000/mm3

4. Severe or chronic renal insufficiency (creatinine clearance = 30 ml/min);

5. Patient unable to follow procedures, visits, examinations described in the study;

6. Any usual formal indication against imaging examinations (important claustrophobia, pacemaker);

Related Conditions & MeSH terms

• Glioblastoma
• Recurrent Glioblastoma

Intervention

Drug:
• Anlotinib
Anlotinib is a multitarget receptor tyrosine kinase inhibitor which inhibits vascular endothelial growth factor receptor (VEGFR) 1-3, fibroblast growth factor receptor (FGFR) 1-4, platelet-derived growth factor receptors (PDGFR) a/ß, c-Kit, and Met.

Locations

Country	Name	City	State
China	Shandong cancer hospital	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Shandong Cancer Hospital and Institute

Country where clinical trial is conducted

China, 

References & Publications (4)

Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13. — View Citation

Lv Y, Zhang J, Liu F, Song M, Hou Y, Liang N. Targeted therapy with anlotinib for patient with recurrent glioblastoma: A case report and literature review. Medicine (Baltimore). 2019 May;98(22):e15749. doi: 10.1097/MD.0000000000015749. Review. — View Citation

Shen G, Zheng F, Ren D, Du F, Dong Q, Wang Z, Zhao F, Ahmad R, Zhao J. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol. 2018 Sep 19;11(1):120. doi: 10.1186/s13045-018-0664-7. Review. — View Citation

Syed YY. Anlotinib: First Global Approval. Drugs. 2018 Jul;78(10):1057-1062. doi: 10.1007/s40265-018-0939-x. Review. Erratum in: Drugs. 2018 Aug;78(12):1287. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress free survival (PFS)	PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.	each 42 days up to PD or death(up to 24 months)
Secondary	Overall Survival (OS)	OS is defined as the time until death due to any cause.	From randomization until death (up to 24 months)
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.	each 42 days up to intolerance the toxicity or PD (up to 24 months)
Secondary	Disease Control Rate (DCR)	Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.	each 42 days up to intolerance the toxicity or PD (up to 24 months)
Secondary	Quality of Life score (QoL)	use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.	each 42 days up to intolerance the toxicity or PD (up to 24 months)