Study of Recombinant Human Endostatin Combined with Temozolomide and Irinotecan in Recurrent Gliomas
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-70
SponsorBeijing Sanbo Brain Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 and ≤70;
Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma);
Recurrence is pathologically confirmed by another biopsy or surgery, which should have been completed at least 2 weeks before enrollment, or confirmed by the MRI according to RANO criteria, at least one bi-dimensionally measurable contrast-enhancing target lesion, with one diameter at least 10 mm, visible on two or more axial slices 5mm apart;
Received standard chemoradiotherapy and at least one cycle of chemotherapy after primary diagnosis;
Disqualifiers
MRI examination is not available (such as pacemaker, metal denture);
Receiving any other investigational agent.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in this study.
Patients who have received organ transplants.
Trial design
Design model
Parallel
Treatments tested in this trial
recombinant human endostatin,temozolomide,irinotecan
DrugTemozolomide 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.
Treatment groups
109 Participants
are divided into 2 treatment groupsGroup A: glioblastomaExperimental treatment 1 intervention
Group B: lower-grade gliomaExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
progression-free survival rate at 6 months
the percentage of participants who remained progression free at 6 months after treatment initiation.
Time frame
up to 4 yearsSecondary outcomes
1
objective response rate
the percentage of patients who achieved confirmed complete response or partial response according to the Response Assessment in Neuro-Oncology (RANO) criteria.
Time frame
up to 4 years2
Progression-free survival
the time interval from treatment initiation to disease progression or death, whichever occurs first.
Time frame
up to 4 years3
Overall survival
the time interval from treatment initiation to death from any cause.
Time frame
up to 4 years4
Safety data
Frequency and severity of adverse effects as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame
up to 4 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov