Efficacy Study of CYT997 in Combination With Carboplatin in Glioblastoma

NCT00650949 | Terminated Phase 1 DMC

• 1 other identifier: CCL08001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

This study seeks to (i) determine the safe dose of CYT997 when given in combination with carboplatin in patients with relapsed glioblastoma multiforme (glioma) and (ii) to determine whether the combination of CYT997 with carboplatin is a useful treatment for glioma.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma multiforme; Glioma; Phase Ib/II; CYT997

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of escalating doses of CYT997 when given in combination with standard carboplatin therapy (Phase Ib component)

  Ongoing throughout therapy up until 30 days after last dose of CYT997

• Progression-free survival at 6 months (PFS-6) utilising the dose of CYT997 identified in the Phase Ib component of this study (Phase II component)

  6 months after initiation of therapy

Secondary Outcomes (5)

• Objective response rate (ORR)

  Response is measured every second cycle of therapy

• Overall survival

  Baseline to study completion

• Safety and tolerability

  Measured continuously from study commencement through to 30 days after last dose of CYT997

• Effects on pharmacodynamic markers of vascular disruption and tumour apoptosis

  Measured during first cycle of therapy

• Pharmacokinetic analysis of carboplatin and CYT997 in combination

  Assessed during first cycle of therapy

Study Arms (1)

CYT997

EXPERIMENTAL

Drug: CYT997; Drug: Carboplatin

Interventions

CYT997 DRUG

Escalating doses (100mg/m\^2 to 150mg/m\^2), 24-hour intravenous infusion on Day 2 of a 21-day cycle (Phase Ib component). Dose selected in Phase Ib component to be used for Phase II component.

CYT997

Carboplatin DRUG

Intravenous infusion over 1 hour at area under the concentration-time curve (AUC)=5 on Day 1 of a 21-day cycle

CYT997

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically-confirmed glioblastoma multiforme that has progressed after initial surgery, radiation therapy and temozolomide chemotherapy.
• Measurable tumour must be present on gadolinium-enhanced MRI
• At least 3 months must have elapsed from completing radiation to minimize the possibility of pseudo-progression.
• At least 4 weeks since prior chemotherapy (6 weeks if the last regimen included bischloroethylnitrosourea (BCNU) or Chloroethyl-Cyclohexyl-NitrosoUrea (CCNU)).
• Age ≥ 18 years.
• If patients are taking steroids, the dose must be stable for = 7 days.
• Eastern Cooperative Oncology Group (ECOG) performance status = 2.
• Life expectancy of greater than 2 months.
• Patients must have adequate organ and marrow function as defined below:
• Absolute neutrophil count = 1.5 × 109/L
• Platelet count = 100 × 109/L
• Total bilirubin within normal limits
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 5 × upper limit of normal (ULN)
• Creatinine within normal limits OR creatinine clearance = 60 mL/min/1.73 m2 for patients with creatinine levels above normal
• Normal left ventricular ejection fraction on a gated blood pool scan or echocardiogram

You may not qualify if:

• Patients who have received any other investigational agent in the preceding four weeks prior to commencing therapy in this study.
• Patients who have been previously treated with carboplatin.
• Patients who have been previously treated with bevacizumab or other anti-angiogenesis or vascular-disrupting agents
• Patients who are receiving enzyme-inducing anticonvulsant drugs (EIACD) such as phenytoin or carbamazepine.
• Patients with a history of allergic reactions attributed to compounds of similar chemical composition to CYT997 or other agents used in the study.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or lactating women.
• Patients with immune deficiency, including HIV-positive patients.
• Patients with uncontrolled diarrhoea despite optimal medication and those with any history of acute gastrointestinal bleeding.
• Patients who are unable or unwilling to undergo MRI scanning
• Patients with the following conditions/treatments will be excluded:
• Myocardial infarction (MI) or stroke within 6 months
• History of stroke or transient ischemic attacks (TIAs)
• Unstable angina pectoris or acute ischemic changes on ECG
• History of diabetic retinopathy

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (4)

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Gold Coast Hospital

Southport, Queensland, 4215, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

CYT997; Carboplatin

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Jason Lickliter, MD

  Peninsula Health

  STUDY CHAIR

• Helen Wheeler, MD

  Royal North Shore Hospital

  PRINCIPAL INVESTIGATOR

• Ganessan Kichenadasse, MD

  Flinders Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: April 2, 2008
• Study Start: November 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: May 3, 2013

Record last verified: 2013-04

Locations

AU (4)