Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00650949
Other study ID # CCL08001
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received March 27, 2008
Last updated April 25, 2013
Start date November 2009
Est. completion date June 2011

Study information

Verified date April 2013
Source Gilead Sciences
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods Administration
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 20
Est. completion date June 2011
Est. primary completion date June 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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

- Must agree to use adequate contraceptive measures if indicated

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- 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

- Symptomatic peripheral arterial disease o Major surgery in the last 4 weeks

- Evidence of intra-tumoural haemorrhage on imaging, except for stable grade-1 post-operative haemorrhage.

- Current therapeutic anti-coagulation with warfarin or a heparin (excludes lowdose prophylactic heparin).

- Uncontrolled hypertension

- The need for any anti-arrhythmic drugs

- Presence of luminal stenosis of 50% or more in any of the extracranial or intracranial arteries supplying the brain, as measured by magnetic resonance angiography (MRA) at baseline.

- Patients with a baseline prolongation of the QTc interval of Common Terminology Criteria (CTC) grade 1 (QTc > 0.45- 0.47 sec) or greater.

- Patients with impaired cardiac function or clinically significant cardiac diseases, including any one of the following:

- Left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram;

- complete left bundle branch block;

- obligate use of a cardiac pacemaker;

- congenital long QT syndrome;

- history or presence of ventricular tachyarrhythmia;

- presence of unstable atrial fibrillation (ventricular response > 100 bpm) Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria;

- clinically significant resting bradycardia (< 50 bpm);

- right bundle branch block + left anterior hemiblock (bifascicular block);

- angina pectoris = 3 months prior to starting study drug;

- acute MI = 3 months prior to starting study drug; or

- other clinically significant heart disease (e.g., congestive heart failure (CHF), uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).

- Patients currently receiving treatment with medications known to prolong the QTc interval and/or to induce Torsades de Pointes arrhythmia.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
CYT997
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.
Carboplatin
Intravenous infusion over 1 hour at area under the concentration-time curve (AUC)=5 on Day 1 of a 21-day cycle

Locations

Country Name City State
Australia Flinders Medical Centre Bedford Park South Australia
Australia Monash Medical Centre Melbourne Victoria
Australia Gold Coast Hospital Southport Queensland
Australia Royal North Shore Hospital St-Leonards New South Wales

Sponsors (1)

Lead Sponsor Collaborator
Gilead Sciences

Country where clinical trial is conducted

Australia, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Yes
Primary 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 No
Secondary Objective response rate (ORR) Response is measured every second cycle of therapy No
Secondary Overall survival Baseline to study completion No
Secondary Safety and tolerability Measured continuously from study commencement through to 30 days after last dose of CYT997 Yes
Secondary Effects on pharmacodynamic markers of vascular disruption and tumour apoptosis Measured during first cycle of therapy No
Secondary Pharmacokinetic analysis of carboplatin and CYT997 in combination Assessed during first cycle of therapy No
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05023551 - Study of DSP-0390 in Patients With Recurrent High-Grade Glioma Early Phase 1
Recruiting NCT06059690 - Biologic Association Between Metabolic Magnetic Resonance-positron Emission Tomograph (MR-PET) and Tissue Measures of Glycolysis in Brain Tumors of Infiltrating Glioblastoma Cells Phase 1/Phase 2
Recruiting NCT04116411 - A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients Phase 2
Terminated NCT01902771 - Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors Phase 1
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Completed NCT00038493 - Temozolomide and SCH66336 for Recurrent Glioblastoma Multiforme Phase 2
Withdrawn NCT03980249 - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells Early Phase 1
Recruiting NCT01923922 - CT Perfusion in the Prognostication of Cerebral High Grade Glioma N/A
Completed NCT01956734 - Virus DNX2401 and Temozolomide in Recurrent Glioblastoma Phase 1
Completed NCT01301430 - Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme. Phase 1/Phase 2
Suspended NCT01386710 - Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma Phase 1/Phase 2
Completed NCT01402063 - PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation Phase 2
Active, not recruiting NCT00995007 - A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas Phase 2
Terminated NCT01044966 - A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma Phase 1/Phase 2
Terminated NCT00990496 - A Study Using Allogenic-Cytomegalovirus (CMV) Specific Cells for Glioblastoma Multiforme (GBM) Phase 1
Completed NCT00402116 - Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients Phase 1/Phase 2
Completed NCT00112502 - Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme Phase 2
Completed NCT00504660 - 6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients Phase 2
Recruiting NCT05366179 - Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc Phase 1