Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Glioblastoma

Disease Attributes

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Temozolomide

Endostatins

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Angiogenesis Inhibitors

Growth Inhibitors

Temozolomide was given orally 200mg/m2 for 5 days in each cycle. Day 1 TMZ was administered 3-6 hours prior to irinotecan.

Irinotecan was administrated 125mg/m2 on day 1 and day 15. Recombinant human endostatin was administrated 15mg/d, daily for 14 days. One treatment cycle was defined as 28 days (4 weeks), even if treatment is held mid-cycle for toxicity.

Treatment was continued until disease progression, patient withdrawal, or unacceptable toxicity.

The maximum number of treatment cycles was 12. After 12 cycles of treatment, if the investigator judges that the subject may continue to benefit from the regimen, the duration of treatment may be extended with the subject's consent.

recombinant human endostatin,temozolomide,irinotecan

Jun-ping Zhang

Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan, the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about 21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent lower-grade gliomas was 40%. The optimal chemotherapeutics of recurrent gliomas has yet to be determined.

Anti-angiogenesis is a promising therapeutic strategy. Vascular endothelial growth factor-A (VEGF) is the primary driver of angiogenesis in tumors. Bevacizumab, a humanized monoclonal antibody directed against VEGF, is the prototypical anti-angiogenic drug and received accelerated approval of the United States Food and Drug Administration (FDA) for the treatment of recurrent glioblastoma. Bevacizumab inproved the PFS-6% (36%), but had no effect on the overall survival (OS) (9.2 months). Moreover, the effects of bevacizumab are transient and most patients' tumors progress just after a median time of 3-5 months. Recombinant human endostatin (rh-ES) is an endogenous broad-spectrum angiogenesis inhibitor that has been shown to significantly improve therapeutic efficacy when combining with conventional chemotherapy agents in non-small-cell lung cancer, breast cancer and melanoma.

In our previous study, we retrospectively analyzed the effect and toxicity of rh-ES when combined with temozolomide and irinotecan on adult recurrent disseminated glioblastoma. After combined treatment, PFS-6% was 23.3%; the median PFS and OS were 3.2 and 6.9 months, respectively, which were promising compared with that in other studies. Once patients get radiographic remission in a short time (4 months), they may get a long PFS.The combined regimen did not reduce the sensitivity of tumor to bevacizumab. After tumor progression from the combined chemotherapy, bevacizumab usage could help to prolong the survival time (5.1 months versus 2.4 months). Moreover, the toxicities of the combination therapy in this study were manageable.

On the basis of prior clinical experience, we carry out this prospective trial to confirm the efficacy and safety of the combination of rh-ES, temozolomide and irinotecan in patients with recurrent gliomas.

Study of Recombinant Human Endostatin Combined With Temozolomide and Irinotecan in Recurrent Gliomas

Open-label Prospective Study of Recombinant Human Endostatin Combined With Cytotoxic Chemotherapy Regimen in the Treatment of Recurrent Gliomas

the percentage of participants who remained progression free at 6 months after treatment initiation.

the percentage of patients who achieved confirmed complete response or partial response according to the Response Assessment in Neuro-Oncology (RANO) criteria.

the time interval from treatment initiation to disease progression or death, whichever occurs first.

the time interval from treatment initiation to death from any cause.

Frequency and severity of adverse effects as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Beijing Sanbo Brain Hospital

Chief physician

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Amino Acids

Dacomitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations.

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.

PF-299804 (Dacomitinib)

Juan Sepúlveda, MD

This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of dacomitinib in adult patients with recurrent Glioblastoma (GBM) with EGFR gene amplification and/or EGFRvIII mutation.

Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.

Phase II Pilot, Prospective, Open Label, Multicenter CT, to Evaluate the Safety and Efficacy of PF299804, a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation

Percentage of patients who have progressed / no progress after 6 months of treatment in each of the two cohorts.

Type, incidence, severity, frequency, severity and relationship with IMP of reported adverse events, physical examinations and laboratory tests. Toxicity will be classified and tabulated by NCI-CTCAE v 4.0.

According to RANO criteria. Based on neurological symptoms, doses of dexamethasone and radiological response, assessed by the PI of each center. There will be central review of MRI.

Time from randomization to death by any cause.

Time from first objective response up to disease progression according RANO (in patients with objective responses).

Percentage of patients decreasing doses of corticosteroids during treatment.

By means of minimental test, it will be determined the changes in neurological status of patients.

Pfizer

Grupo Español de Investigación en Neurooncología

Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations.

PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.

Age, Continuous

Sex: Female, Male

Spain

Region of Enrollment

O6-Methylguanine-DNA Methyltransferase (MGMT) is a DNA repair enzyme that removes alkyl adducts from the O6 position of guanine.

Methylation of the MGMT promoter has been reported in several tumor types.

MGMT methylation status

Mutations in isocitrate dehydrogenase (IDH) 1 and 2 occur in the vast majority of low grade gliomas and secondary high grade gliomas. These mutations change the function of the enzymes, causing increased methylation in gliomas. Gliomas with mutated IDH1 and IDH2 have improved prognosis compared to gliomas with wild-type IDH

IDH1/2 mutational status

The scale was developed by the Eastern Cooperative Oncology Group (ECOG). It describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 (fully independent), 1 (Restricted in physically strenuous activity but ambulatory ), 2 (Ambulatory and capable of all selfcare but unable to carry out any work activities), 3 (Capable of only limited selfcare), 4 (Completely disabled) to 5 (death).

ECOG performance status

Important limitations of our study are the small sample size and the nonrandomized design, which preclude drawing firm conclusions, EGFR amplification, which has been used as a primary laboratory assessment, was tested in the primary tumor, and we have no evidence of the stability of this alteration in the recurrent GBs.

Pau Doñate

Cohort A

Cohort B

Patients were analyzed stratified by cohorts according to their EGFR mutational status: Cohort A included patients with EGFR gene amplification without EGFRvIII mutation. Cohort B included patients with EGFR gene amplification and EGFRvIII mutation.

Progression-free Survival (PFS) at Six Months (PFS6m)

Any grade Adverse event

Grade 3 or higher Adverse envent

Safety population. All patients that were enrolled and received at least 1 dose of study treatment

Safety and Tolerability of Oral Administration of PF-00299804.

The analisis was stratified by cohort according to their EGFR mutational status

Anti-tumor Response

Full data set

2 patients were not evaluable because they withdrawn their consent Data is reported stratified by cohort according to their EGFR mutational status

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Recombinant Human Endostatin Combined With Temozolomide and Irinotecan in Recurrent Gliomas	NCT04267978	Glioblastoma, R... Lower Grade Gli...	recombinant hum...	18 Years - 70 Years	Beijing Sanbo Brain Hospital
Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.	NCT01520870	Glioblastoma Brain Tumor, Re...	PF-299804 (Daco...	18 Years -	Grupo Español de Investigación en Neurooncología
Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.	NCT01520870	Glioblastoma Brain Tumor, Re...	PF-299804 (Daco...	18 Years -	Grupo Español de Investigación en Neurooncología

Spots Global Cancer Trial Database for glioblastoma, recurrent