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

NCT ID: NCT02263105

Last Updated: 2018-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2018-06-30

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.

Conditions

High-grade Gliomas

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CDDP plus Temozolomide

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

Group Type: EXPERIMENTAL

CDDP

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

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.

Interventions

CDDP

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhang Zhenyu

M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiyong Qin, MD

Role: STUDY_CHAIR

Huashan Hospital

Ying Mao, MD

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Yu Yao, MD

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

ZhenYu Zhang

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Locations

Huashan Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

Huashan H

Identifier Type: OTHER

Identifier Source: secondary_id

CAT001

Identifier Type: -

Identifier Source: org_study_id