High-grade Gliomas
Conditions
Keywords
recurrent high-grade gliomas, cisplatin (CDDP), temozolomide (TMZ)
Brief summary
Currently, the prognosis of recurrent high-grade gliomas is still dismal with no standard treatment protocol established. Cisplatin (CDDP), recommended by National Comprehensive Cancer Network (NCCN) as a chemotherapeutic agent in salvage treatment for recurrent high-grade gliomas, was shown to reduce O6-alkylguanine DNA-alkyl transferase (AGAT) activity and potentially capable of enhancing the antitumor effects of temozolomide (TMZ). Compared to the standard 5-day TMZ regimen, alternating weekly regimen that deliver more prolonged exposure of TMZ may lead to higher cumulative doses, and may deplete more O6-methylguanine DNA methyltransferase (MGMT), thus reducing the resistance of tumor cells to TMZ. The investigators therefore initiate a single-arm Phase II study to evaluate the efficacy and tolerability of CDDP plus alternating weekly TMZ regimen in patients with recurrent high-grade gliomas.
Interventions
DRUGCDDP
DRUGTemozolomide
If hematologic and nonhematologic toxicity assessed according to the Common Terminology Criteria for Adverse Events (CTCAE; version 4.0) from the previous cycle had been grade 0 or 1, then TMZ dose escalation to was allowed to the maximum of 150 mg/m2. If grade 4 hematologic toxicity or grade 3 nonhematologic toxicity had occurred, then TMZ dose was reduced in 25 mg/m2 steps. If grade 4 nonhematologic toxicity occurred, patient treatment was halted. If grade 4 hematologic toxicity or grade 3 nonhematologic toxicity continued when TMZ dose was in the minimum of 75 mg/m2, patient treatment was halted.
Sponsors
Huashan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histological diagnosis of primary tumor as high-grade gliomas (WHO III or IV) * All patients should complete radiation therapy for primary gliomas. * MRI showed unequivocal evidence of tumor recurrence or progression. * The time to be enrolled should be more than 90 days after the radiation therapy. * Written informed consent * Eastern Cooperative Oncology Group(ECOG) score: 0-2 * The patients with recurrent gliomas were treated without dose-dense TMZ therapy before enrollment. * Surgical interventions for recurrent gliomas are permitted and patients with no residual tumor are permitted
Exclusion criteria
* Abnormal function of liver or renal (value more than 1.5 fold normal upper limit) * Blood routing: Hb \< 90g/L, absolute neutrophil count≤1.5\*10\^9/L, platelet \< 100\*10\^9/L * Pregnant or lactating women * Allergic to administered drugs * Radiation therapy in the previous 90 days before enrollment * The patients with recurrent gliomas were treated with dose-dense TMZ therapy before enrollment. * Acute infection in need of antibiotics intravenously * Participation in other clinical trials in the 90 days before enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progression free survival (PFS) | at 6 months |
Secondary
| Measure | Time frame |
|---|---|
| overall survival(OS) | at 1 year and 2 years |
Countries
China
Outcome results
None listed