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

Phase 2
Completed
Conditions
High-grade Gliomas
Interventions
Registration Number
NCT02263105
Lead Sponsor
Huashan Hospital
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
67
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
CDDP plus TemozolomideCDDPPatients 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) 1. 150 2100 2. 125 1750 3. 100 1400 4. 75 1050
CDDP plus TemozolomideTemozolomidePatients 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) 1. 150 2100 2. 125 1750 3. 100 1400 4. 75 1050
Primary Outcome Measures
NameTimeMethod
progression free survival (PFS)at 6 months
Secondary Outcome Measures
NameTimeMethod
overall survival(OS)at 1 year and 2 years

Trial Locations

Locations (1)

Huashan Hospital

🇨🇳

Shanghai, Shanghai, China

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