Apatinib in Recurrent or Refractory Intracranial Central Nervous System Malignant Tumors

Efficacy and Safety of Apatinib Combined With Dose-dense Temozolomide in Recurrent Glioblastoma

The patient was given a daily dose of apatinib 500mg (or based on weight). Individualized chemotherapy regimens were given based on molecular expression and prior chemotherapy.

Study Overview

• Status: Completed
• Conditions: Efficacy and Safety
• Intervention / Treatment: Drug: apatinib; Drug: temodar

Detailed Description

The patient was given a daily dose of apatinib 500mg (or based on weight). Individualized chemotherapy regimens were given based on molecular expression and prior chemotherapy. Brain MRI+MRS was examined every 3 months; Blood routine, urine routine and liver and kidney function were examined once a week.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Neurosurgery, Shandong Cancer Hospital and Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) 18 years < the age of patients > 70 years. (2) Karnofsky performance scale (KPS) ≥ 60. (2) Histologically confirmed diagnosis of GBM World Health Organization [WHO] Grade IV. (3) They were required to have measurable or evaluable disease by magnetic resonance imaging (MRI) confirmation and a minimum life expectancy of 8 weeks. (4) Definition of relapse: all patients must have progressive disease on MRI defined by Response Assessment in Neuro-Oncology (RANO) criteria after the standard Stupp protocol. The time interval for the start of treatment was at least 12 weeks from prior radiotherapy unless there was either histopathologic confirmation of recurrent tumor or new contrast enhancement on MRI outside of the radiotherapy treatment field. (5) Adequate bone marrow function (leukocyte count ≥ 4000/μL, neutrophil count ≥1500/µL, platelet count ≥100 000/µL, hemoglobin ≥8.0g/dL), adequate renal function (serum creatinine ≤ 150μmol/L, 24 hours urine protein ≤3.4g), and liver function (total bilirubin ≤34μmol/L and aspartate and alanine aminotransferase ≤120U/L).

Exclusion Criteria:

• (1) extracranial metastatic disease, (2) Gliadel wafer treatment, (3) severe cardiopulmonary insufficiency, (4) status epilepticus, (5) pregnancy, (6) gastrointestinal bleeding, (7) uncontrolled blood pressure with medication (>140/90 mm Hg), (8) swallowing difficulties. (9) HIV positivity with a combination antiretroviral therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: apatinib 500mg

Drug: apatinib; The patient was given a daily dose of apatinib 500mg (or based on weight). For adult, the dose of apatinib was prescribed with 425 mg or 500 mg per day and four weeks for a cycle. The dosage was modified to 250 mg if patients experienced ≧grade 2 hematologic adverse events, hand and foot syndrome, proteinuria, fecal ocular blood, or grade 3/4 hypertension, or other grade 3/4 adverse events. Apatinib was administrated until disease progression, unacceptable toxicity or death.; Drug: temodar; dose-dense temozolomide (100 mg/m2 , 7 days on with 7 days off ) , 28d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to treatment	Response were evaluatedevery 1-3 months with Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST 1.0) usingdynamic contrast enhancement magnetic resonance imaging (MRI) or computed tomography (CT). Complete response (CR) was defined as complete disappearance of target lesions and maintaining ≥ 4 weeks; partial response (PR): ≥ 30% reduction in maximum diameterof tumor and keepingstable ≥ 4 weeks; progressive disease (PD):>20% increase in bidimensionalmeasurements of the lesions, or emerging one or more newlesions; stable disease (SD): criteria for CR, PR and PDnot met.PFS was defined as the initial treatment to the disease progression or the date of death.	up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median non-progress survival (PFS)	Median non-progress survival (PFS)	up to 12 months

Collaborators and Investigators

• Sponsor: Rongjie Tao

Publications and helpful links

General Publications

• Kasper H. [The supplying of vitamin A after pancreatectomy]. Med Welt. 1968 Jan 20;3:178-80. No abstract available. German.
• Potapova TV, Sharovskaia IuIu, Kovalev SA, Mittel'man LA, Chailakhian LM. [Effect of the ion composition of the surrounding medium on membrane potentials of L cells]. Tsitologiia. 1972 Nov;14(11):1335-41. No abstract available. Russian.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2016
• Primary Completion (Actual): January 3, 2017
• Study Completion (Actual): January 6, 2018

Study Registration Dates

• First Submitted: August 11, 2018
• First Submitted That Met QC Criteria: September 4, 2018
• First Posted (Actual): September 7, 2018

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 14, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Protein Kinase Inhibitors; Temozolomide; Apatinib
• Other Study ID Numbers: ShandongCHI005

Drug and device information, study documents

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