The general objectives are to assess the safety of combining dasatinib with CCNU as well as to assess activity of this combination and CCNU alone in GBM patients who have relapsed after prior treatment with temozolomide and radiotherapy
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To estimate the proportion of subjects surviving without progression at 6
months (PFS-6) within the combination treatment arm (dasatinib plus CCNU).
Secondary outcome
1. Kaplan-Meier estimates of median PFS and PFS-6 (CCNU arm) and PFS-12.
2. Median overall survival and at 12 and 24 months.
3. Best overall response distribution, objective and complete response rates
and median duration of objective or complete response.
4. Descriptive comparison of Time To Progression
5. Percentages of worst adverse events or Lab adverse events per AE term and
category.
6. Correlation of angiogenesis and hypoxia markers expression and MGMT
methylation status with clinical outcome.
Background summary
There is no *standard* nor widely-accepted treatment for patients with
recurrent glioma. The median survival of patients with recurrent GBM is
approximately 4 months, or approximately 6 months if a second resection is
undertaken. Recurrent GBM therefore represents a clear unmet clinical need.
There are very few agents which exert activity in GBM patients. Among these
nitrosureas are probably the mostly widely used and lomustine (CCNU) falls
under this class of cytotoxic agent. Because of the presence of a multitude of
collateral upregulated signalling pathways in glioblastoma, the early
exploration of combination treatments are an attractive alternative scenario.
Study objective
The general objectives are to assess the safety of combining dasatinib with
CCNU as well as to assess activity of this combination and CCNU alone in GBM
patients who have relapsed after prior treatment with temozolomide and
radiotherapy
Study design
The trial will integrate a non-randomised safety cohort aimed at documenting
the safety profile and recommended dose of dasatinib in combination with CCNU,
followed by a randomised Phase II study which will address the overall
therapeutic strategy on combining dasatinib and CCNU or CCNU alone.
Intervention
Either Lomustine (oral) as a single therapy or Lomustine + Dasatinib (oral) as
a combined therapy
Study burden and risks
Patients will be subject to invasive medical procedures (blood sampling, ECGs,
MRIs, ECGs and chest X-Rays) but these procedures will be performed by trained
medical staff so any risks or pain associated with these procedures should be
minimised. The most commonly reported toxicities from either drug treatment is
myelosuppression, nausea and vomiting as well as those as listed in the
Informed consent form, some of which can be severe in nature. However, patients
will be followed closely for toxicities and appropriate medical care given and
based on previous human studies, these toxicities are manageable.
Vijzelmolenlaan 9
3440 AM Woerden
NL
Vijzelmolenlaan 9
3440 AM Woerden
NL
Listed location countries
Age
Inclusion criteria
1. Histologically- or cytologically-proven glioblastoma multiforme including anaplastic oligoastrocytoma with necrosis
2. Completion of Prior radiotherapy to brain > 3 months prior to the diagnosis of progression.
3. Recurrent disease documented by MRI scan within two weeks prior to start of study treatment.
4. No other chemotherapy regimens apart from Temozolomide are allowed. 5. Prior exposure in the adjuvant setting to biotherapies or a targeted agent is allowed if at least 4 weeks have elapsed since end of treatment and patients have recovered for all toxicities.
6. Patients may have been operated for recurrence. Surgery should be completed for at least 2 weeks before registration and patients should have fully recovered. An immediate (within 48hrs hours) MRI should be performed to document measurable residual disease
7. For non operated patients, recurrent disease must have at least one bidimensional target lesion of at least 2cm based on a MRI scan done within 2 weeks prior to registration.
10. Safety cohort only- Patients respiratory function (evaluated by DCLO) must be >60% of the predicted value.
11. Age >=18 years
12. WHO Performance status 0 - 2
13. Must be on a stable or decreasing dose of corticosteroids for at least 1 week prior to treatment start
14. Normal hematologic values
15. Normal liver function
16. Clinically normal cardiac function without history of ischemic heart disease in the past 12 months. Absence of cardiac insufficiency NYHA grade III and IV, instable angina & arrhythmia.
Exclusion criteria
1. No prior chemotherapy for recurrent disease.
2. No prior Gliadel wafers.
3. If any high-dose radiotherapy (> 65 Gy), stereotactic radiosurgery or internal radiation therapy has been performed, recurrence must be histologically confirmed.
4. No other malignancy [with exception of cone biopsied carcinoma of the cervix or treated basal or squamous cell skin carcinoma] in previous 3 years
5. All subjects (male and female) of reproductive potential must use effective contraception. Females must not be pregnant at entry or lactating.
6. Subjects should not be taking antiepileptic agents or be on non-enzyme-inducing antiepileptic drugs (non-EIAEDs).
7. No history of pulmonary disease that may affect pulmonary functions including obstructive chronic broncho-pneumopathy, concurrent pleural effusion and interstitial pneumonia.
8. No psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-010576-21-NL |
| CCMO | NL28942.091.09 |
| Other | volgt midden juli2009 |