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

NCT02263105 | Completed Phase 2

• 2 other identifiers: CAT001Huashan H
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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

Keywords

recurrent high-grade gliomas; cisplatin (CDDP); temozolomide (TMZ)

Outcome Measures

Primary Outcomes (1)

• progression free survival (PFS)

  at 6 months

Secondary Outcomes (1)

• overall survival(OS)

  at 1 year and 2 years

Study Arms (1)

CDDP plus Temozolomide

EXPERIMENTAL

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

Drug: CDDP; Drug: Temozolomide

Interventions

CDDP DRUG

CDDP plus Temozolomide

Temozolomide 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.

CDDP plus Temozolomide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (1)

Huashan Hospital

Shanghai, Shanghai Municipality, 200040, China

Location

MeSH Terms

Interventions

Temozolomide

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Zhiyong Qin, MD

  Huashan Hospital

  STUDY CHAIR

• Ying Mao, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

• Yu Yao, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

• ZhenYu Zhang

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: September 28, 2014
• First Posted: October 13, 2014
• Study Start: October 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: June 1, 2018
• Last Updated: July 17, 2018

Record last verified: 2018-07

Locations

CN (1)