Clinical Study on the Treatment of Recurrent Glioblastoma With Anlotinib

Phase 1

• Conditions: Recurrent Glioblastoma
• Interventions: Drug: Anlotinib

• Registration Number: NCT04004975
• Lead Sponsor: Shandong Cancer Hospital and Institute

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);

Study Timeline

• Study Start: 2019-06-25
• Status Verified: 2019-07
• Study First Submitted: 2019-07-01
• Study First Submitted QC: 2019-07-01
• Last Update Submitted: 2019-07-01
• Study First Posted: 2019-07-02
• Last Update Posted: 2019-07-02
• Primary Completion: 2020-07-25
• Study Completion: 2021-07-25

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anlotinib	Anlotinib	12 mg daily from day 1 to 14 of a 21-day cycle

Primary Outcome Measures

Name	Time	Method
Progress free survival (PFS)	each 42 days up to PD or death(up to 24 months)	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.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	each 42 days up to intolerance the toxicity or PD (up to 24 months)	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.
Quality of Life score (QoL)	each 42 days up to intolerance the toxicity or PD (up to 24 months)	use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.
Overall Survival (OS)	From randomization until death (up to 24 months)	OS is defined as the time until death due to any cause.
Disease Control Rate (DCR)	each 42 days up to intolerance the toxicity or PD (up to 24 months)	Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.

Trial Locations

Locations (1)

Shandong cancer hospital; 🇨🇳 Jinan, Shandong, China