GlioblastomaPhase 1NCT00884416
Sorafenib in Newly Diagnosed High Grade Glioma
A Phase 1 study testing Sorafenib dose escalation in people with Glioblastoma and Gliosarcoma, run by University Hospital, Geneva at 1 site in Switzerland.
Trial summary
This is a phase I study to evaluate the safety and tolerability of Sorafenib in combination with Temodar and radiation therapy in patients with newly diagnosed high grade glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma and anaplastic oligodendroglioma or oligoastrocytoma). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma
- What is being tested?
- Sorafenib dose escalation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteSwitzerland
- Study dates
- Mar 2009to Mar 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological documentation of newly diagnosed malignant glioma
- ECOG performance status of 0 or 1
- Age ≥18
- Life expectancy of at least 12 weeks
- Hemoglobin ≥ 9.0 g/dl
- Granulocyte count ≥1.5 X 10^9/L
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- Platelet count ≥100 X 10^9/L
- SGOT ≤ 2.5X upper limit of normal (ULN)
- SGPT ≤ 2.5X upper limit of normal (ULN)
- Alkaline phosphatase ≤4x ULN
- Serum creatinine ≤1.5X ULN
- Bilirubin ≤1.5X ULN
- Spontaneous PT-INR/PTT < 1.5x upper limit of normal (patients on therapeutic anticoagulation will be allowed to participate.
- Patients must be on a stable or decreasing dose of corticosteroids for at least 2 weeks
- Patient for whom a first line treatment with temozolomide and radiotherapy is adequate
- Prophylactic anti-emetic, pentamidine inhalation / co-trimoxazole and anticonvulsants are allowed
- All patients must sign written informed consent.
Who cannot join
- Prior treatment for high grade glioma
- Previous exposure to Ras pathway inhibitors
- Other concurrent active malignancy (with the exception of cervical carcinoma in situ or non melanoma carcinoma of the skin, superficial bladder tumor [Ta, Tis \& T1] or any cancer curatively treated > 3 years prior to study entry).
- Serious medical or psychiatric illness that would, in the opinion of the investigator, interfere with the prescribed treatment, including but not limited to: Congestive heart failure > NYHA class 2, active CAD, cardiac arrythmias requiring anti-arrythmic therapy or uncontrolled hypertension within the last 12 months
- Any condition limiting the patient's judgment capacity
- History of HIV infection, chronic hepatitis C or B as well as clinically active infections (> grade 2 NCI-CTC version 3.0)
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- History of organ allograft
- Renal dialysis
- Evidence or history of bleeding diathesis
- Major surgery within 4 weeks of start of study treatment, except for neurosurgical resection
- Autologous bone marrow transplant or stem cell rescue within 4 months of study
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results.
- Medical condition that prevents the patient from swallowing pills
- Use of biologic response modifiers, such as G-CSF within 3 week of study entry.
- Pregnant or breast-feeding women.
- Refusal to use effective contraception. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and for at least 3 months after administration of study medication.
- Known or suspected allergy to the investigational agent or any agent given in association with this trial.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Geneva University Hospital (Hopitaux Universitaires de Geneve), Department of Oncology
Geneva, Canton of Geneva, 1211
About this study
Official title: Phase I Dose Finding Study of Sorafenib in Combination With Radiation Therapy and Temozolomide as a First Line Treatment of Patients With High Grade Glioma
This is a phase I study to evaluate the safety and tolerability of Sorafenib in combination with Temodar and radiation therapy in patients with newly diagnosed high grade glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma and anaplastic oligodendroglioma or oligoastrocytoma). The mechanism of action of sorafenib, an oral multikinase inhibitor, makes it an interesting drug to investigate in the treatment of patients with high grade glioma as this agent has anti-angiogenic activity and inhibits other pathways such as Ras, Platelet-derived growth factor (PDGF) and fms-like tyrosine kinase receptor-3 (Flt-3), which are potential targets against gliomas.
Read the detailed description
Up to 18 patients will be included in this phase I study. The primary goal of this study will be to establish the maximum tolerated dose of sorafenib when used in combination with temozolomide and radiation therapy. Secondary goals of this study include: response rate, time to treatment failure, 6 month progression-free survival, event free survival and overall survival. A correlative study will investigate the pharmacokinetics of sorafenib used in combination with radiation therapy and temozolomide.
- Conditions
- Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma, Anaplastic Oligodendroglioma
- Being tested
- Sorafenib dose escalation
- Keywords
- high grade glioma, glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, phase I, first line treatment, sorafenib, temozolomide, radiation therapy, safety, tolerability, protein kinase inhibitors
- Medical subject headings
- Glioblastoma, Gliosarcoma, Astrocytoma, Oligodendroglioma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib dose escalationDrug
Sorafenib dose escalation scheme: 3 first patients: 200 mg/d, if dose limiting toxicities (DLT) not reached: 3 patients at 200 mg BID, if no DLT reached: 3 patients at 400 mg bid
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib dose titration | Experimental | Not described Receives: Drug: Sorafenib dose escalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy
Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy in patients with newly diagnosed high grade glioma
Measured: 35 weeks
Secondary outcomes (6)
Maximum Observed Plasma Concentration (Cmax) and Area under the curve (AUC) of sorafenib and temozolomide
Measured: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post dose
Response rate
Measured: 35 weeks
Time to treatment failure
Measured: 20 months
6 month progression-free survival
Measured: 6 months
Event free survival
Measured: 20 months
Overall survival
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2009 (estimated)
- Study startMar 2009
- Primary completionDec 2011
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Andreas F. Hottinger, University Hospital, Geneva
- Investigators
- Pierre-Yves Dietrich, MD, Principal investigator, Department of oncology, Geneva University hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00884416
- Sponsor's protocol ID
- 08-122
- Other IDs
- 2009DR1029, 13031
- Status last verified
- Oct 2014
- First submitted
- 17 Apr 2009
- Last updated
- 4 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hottinger AF, Ben Aissa A, Espeli V, Squiban D, Dunkel N, Vargas MI, Hundsberger T, Mach N, Schaller K, Weber DC, Bodmer A, Dietrich PY. Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma. Br J Cancer. 2014 May 27;110(11):2655-61. doi: 10.1038/bjc.2014.209. Epub 2014 May 1.
PubMed 24786603
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Finding Study of Sorafenib in Combination With Radiation Therapy and Temozolomide as a First Line Treatment of Patients With High Grade Glioma
- ClinicalTrials.gov ID
- NCT00884416
- Acronym / sponsor ID
- 08-122
- Conditions
- Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma, Anaplastic Oligodendroglioma
- Keywords
- high grade glioma, glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, phase I, first line treatment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Mar 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 20 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I study to evaluate the safety and tolerability of Sorafenib in combination with Temodar and radiation therapy in patients with newly diagnosed high grade glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma and anaplastic oligodendroglioma or oligoastrocytoma). The mechanism of action of sorafenib, an oral multikinase inhibitor, makes it an interesting drug to investigate in the treatment of patients with high grade glioma as this agent has anti-angiogenic activity and inhibits other pathways such as Ras, Platelet-derived growth factor (PDGF) and fms-like tyrosine kinase receptor-3 (Flt-3), which are potential targets against gliomas.
Detailed description
Up to 18 patients will be included in this phase I study. The primary goal of this study will be to establish the maximum tolerated dose of sorafenib when used in combination with temozolomide and radiation therapy. Secondary goals of this study include: response rate, time to treatment failure, 6 month progression-free survival, event free survival and overall survival. A correlative study will investigate the pharmacokinetics of sorafenib used in combination with radiation therapy and temozolomide.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib dose titration | Experimental | Drug: Sorafenib dose escalation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histological documentation of newly diagnosed malignant glioma
- ECOG performance status of 0 or 1
- Age ≥18
- Life expectancy of at least 12 weeks
- Hemoglobin ≥ 9.0 g/dl
Key exclusion criteria (17 listed)
- Prior treatment for high grade glioma
- Previous exposure to Ras pathway inhibitors
- Other concurrent active malignancy (with the exception of cervical carcinoma in situ or non melanoma carcinoma of the skin, superficial bladder tumor [Ta, Tis \& T1] or any cancer curatively treated > 3 years prior to study entry).
- Serious medical or psychiatric illness that would, in the opinion of the investigator, interfere with the prescribed treatment, including but not limited to: Congestive heart failure > NYHA class 2, active CAD, cardiac arrythmias requiring anti-arrythmic therapy or uncontrolled hypertension within the last 12 months
- Any condition limiting the patient's judgment capacity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sorafenib dose escalationSorafenib dose escalation scheme: 3 first patients: 200 mg/d, if dose limiting toxicities (DLT) not reached: 3 patients at 200 mg BID, if no DLT reached: 3 patients at 400 mg bid | Drug | Sorafenib dose titration |
Primary outcome
Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy
Time frame: 35 weeks
Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy in patients with newly diagnosed high grade glioma
6 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) and Area under the curve (AUC) of sorafenib and temozolomide
Time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post dose
Response rate
Time frame: 35 weeks
Time to treatment failure
Time frame: 20 months
6 month progression-free survival
Time frame: 6 months
Event free survival
Time frame: 20 months
Overall survival
Time frame: 20 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2014.
- Results publication: PubMed 24786603Hottinger AF, Ben Aissa A, Espeli V, Squiban D, Dunkel N, Vargas MI, Hundsberger T, Mach N, Schaller K, Weber DC, Bodmer A, Dietrich PY. Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma. Br J Cancer. 2014 May 27;110(11):2655-61. doi: 10.1038/bjc.2014.209. Epub 2014 May 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre-Yves Dietrich, MD principal investigator
Department of oncology, Geneva University hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sorafenib dose escalation in people with Glioblastoma and Gliosarcoma, run by University Hospital, Geneva at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy (time frame: 35 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00884416, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2014.