Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas: A Single-arm Prospective Phase II Clinical Study

Conditions
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High-grade Gliomas

Intervention / Treatment
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* Drug: CDDP
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDDP plus Temozolomide<br>Patients were treated with CDDP and TMZ. CDDP was administered iv from Day 1 to 3 with everyday dose of 30mg. TMZ was orally administered from Day 1 to 7 and Day 15 to 21, with everyday dose of 125mg/m2 (Level 2). The period of one chemotherapy cycle is 28 days. TMZ dose levels were listed in Table 1. Table 1 TMZ dose levels Dose levels Daily TMZ dose( mg/m2/d ) TMZ dose per cycle(mg/m2) 150 2100 125 1750 100 1400 75 1050 | Drug: CDDP<br> <br> Drug: Temozolomide<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival (PFS) |  | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival(OS) |  | at 1 year and 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent high-grade gliomas, cisplatin (CDDP), temozolomide (TMZ)