Clinical trial NCT02263105: Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas
Official title: Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas: A Single-arm Prospective Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: High-grade Gliomas
Keywords: recurrent high-grade gliomas
cisplatin (CDDP)
temozolomide (TMZ)
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2014-10-13
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: progression free survival (PFS)
timeFrame: at 6 months
Secondary outcomes:
measure: overall survival(OS)
timeFrame: at 1 year and 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Zhiyong Qin, MD
role: STUDY_CHAIR
affiliation: Huashan Hospital
name: Ying Mao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Yu Yao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: ZhenYu Zhang
role: PRINCIPAL_INVESTIGATOR
References: