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

High-grade Gliomas Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02263105
• Other study ID #: CAT001
• Secondary ID: Huashan H
• Status: Completed
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: June 2018

Study information

• Verified date: July 2018
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: June 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioma
• High-grade Gliomas

Intervention

Drug:
• CDDP

• Temozolomide
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.

Locations

Country	Name	City	State
China	Huashan Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Huashan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival (PFS)		at 6 months
Secondary	overall survival(OS)		at 1 year and 2 years