Clinical trial NCT04004975: Clinical Study on the Treatment of Recurrent Glioblastoma With Anlotinib
Official title: Phase II Clinical Trials on Anlotinib for the Treatment of Recurrent Glioblastoma.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Recurrent Glioblastoma
Keywords: anlotinib Recurrent Glioblastoma
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2019-07-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: one-armed controlled clinical trial
Primary purpose: TREATMENT

Brief 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.

Detailed 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);

Eligibility criteria: 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);

Primary outcomes:
measure: Progress free survival (PFS)
timeFrame: each 42 days up to PD or death(up to 24 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to 24 months)
measure: Objective Response Rate (ORR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Quality of Life score (QoL)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong cancer hospital
state: Shandong
Study officials:
References:
citation: 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.
citation: Syed YY. Anlotinib: First Global Approval. Drugs. 2018 Jul;78(10):1057-1062. doi: 10.1007/s40265-018-0939-x.
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.
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.