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

Fudan University

Status and phase: Completed; Phase 2

Conditions: High-grade Gliomas

Treatments: Drug: CDDP; Drug: Temozolomide

Study type: Interventional

Funder types: Other

Identifiers

NCT02263105

CAT001

Huashan H (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 67 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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67 participants in 1 patient group

CDDP plus Temozolomide

Experimental group

Description:

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) 1. 150 2100 2. 125 1750 3. 100 1400 4. 75 1050

Treatment:

Drug: Temozolomide

Drug: CDDP