Glioblastoma MultiformePhase 2NCT00544817
Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme
A Phase 2 study testing Radiation Therapy, Temozolomide and Sorafenib in people with Glioblastoma Multiforme, run by SCRI Development Innovations, LLC at 10 sites in United States.
Trial summary
The mechanism of action of sorafenib makes it an interesting drug to investigate in the treatment of patients with glioblastoma multiforme. Efficacy of agents with anti-angiogenic activity has already been demonstrated and the PDGF receptor target may also be pertinent in glioblastoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Radiation Therapy, Temozolomide and Sorafenib
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 10 sitesUnited States
- Study dates
- Apr 2007to Aug 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
- Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
- No previous treatment for glioblastoma except for previous surgical debulking (i.e. no previous radiotherapy, local chemotherapy, or systemic therapy).
- ECOG performance status 0 or 1 (See Appendix C)
- Age ≥ 18 years
- Adequate bone marrow function: hemoglobin ≥ 9.0g/dL; ANC ≥ 1500/μL; platelet count ≥ 100,000/μL.
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- Adequate liver function
- Total bilirubin ≤ 1.5 x ULN
- ALT and AST ≤ 2.5 x ULN
- Serum creatinine < 1.5 x ULN
- Women of child-bearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women must agree to not breast feed while receiving study treatment.
- Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) while receiving study treatment. Women should use adequate birth control for at least 3 months after the last administration of sorafenib.
- INR < 1.5 or PT/PTT within normal limits in patients not receiving anticoagulation. However, patients receiving anticoagulation treatment with an agent such as warfarin or heparin are also eligible. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Patients must have the ability to understand and the willingness to sign written informed consent. A signed informed consent must be obtained prior to any study-specific procedures.
Who cannot join
- Patients must have the ability to swallow whole pills.
- Active cardiac disease: congestive heart failure > class 2 NYHA (Appendix D); unstable angina or new onset angina within the last 3 months; myocardial infarction within the last 6 months.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Uncontrolled hypertension defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optimal medical management
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection
- Active clinically serious infection > grade 2
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- Thrombotic or embolic events including cerebral vascular accident or TIAs within the past 6 months
- Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of the first dose of sorafenib
- Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of the first dose of sorafenib
- Serious non-healing wound, ulcer, or bone fracture
- Evidence or history of bleeding diathesis or coagulopathy
- Major surgery, open biopsy, or significant traumatic injury within 4 weeks of beginning treatment with sorafenib
- Use of St. John's Wort or rifampicin
- Known or suspected allergy to sorafenib or temozolomide
- Any malabsorption problem
- Other active malignancies, or treatment for invasive cancer within the last 2 years
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Oncology Hematology Care
Cincinnati, Ohio, 45242
Florida Cancer Specialists
Fort Myers, Florida, 33901
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, 49503
Tennessee Oncology
Nashville, Tennessee, 37203
Methodist Cancer Center
Omaha, Nebraska, 68114
Virginia Cancer Institute
Richmond, Virginia, 23235
South Texas Oncology and Hematology
San Antonio, Texas, 78258
Spartanburg Regional Medical Center
Spartanburg, South Carolina, 29303
About this study
Official title: A Phase II Trial of Concurrent Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib in the First-Line Treatment of Patients With Glioblastoma Multiforme
The mechanism of action of sorafenib makes it an interesting drug to investigate in the treatment of patients with glioblastoma multiforme. Efficacy of agents with anti-angiogenic activity has already been demonstrated and the PDGF receptor target may also be pertinent in glioblastoma. The combination of temozolomide plus sorafenib has been investigated previously in the treatment of patients with advanced melanoma. The combination was generally well tolerated; in previously untreated patients, a standard dose of sorafenib (400mg PO bid) was administered with temozolomide 150mg/m2 PO daily for 5 days, repeated every 28 days (23).
In this multicenter phase II study, patients with newly diagnosed glioblastoma will receive standard treatment, including initial debulking surgical resection (if feasible) followed by high-dose radiation therapy with concurrent temozolomide. After completion of radiation therapy, patients will continue treatment with temozolomide (150mg/m2 days 1-5) and sorafenib (400mg PO bid daily), repeated at 28-day intervals for 6 cycles.
Read the detailed description
All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.
Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.
After completion of combined modality therapy, patients will have 4 weeks without any therapy.
Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be administered on days 1-28, repeated for 6 courses concurrently with temozolomide
- Conditions
- Glioblastoma Multiforme
- Being tested
- Radiation Therapy, Temozolomide, Sorafenib
- Keywords
- Concurrent Radiation Therapy, Temozolomide, Sorafenib, First-line, Glioblastoma Multiforme, Phase II
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation TherapyRadiation
2 Gy/fraction, single daily fractions M-F, to 60 Gy total
TemozolomideDrug
Also called Temodar
In Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily
In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles
SorafenibDrug
Also called Nexavar
In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | In the combined modality portion of the study, patients were administered:
Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily
Patients took a four week break before beginning follow-up systemic therapy:
Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months Receives: Radiation: Radiation Therapy; Drug: Temozolomide; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
Measured: 18 months
Secondary outcomes (2)
Overall Survival
Defined as Day 1 of protocol treatment to date of death from any cause.
Measured: 18 months
Objective Response
The number of patients with complete or partial responses measured from the time of initial response to documented tumor progression. Radiologic response was defined using the Macdonald criteria.
The Macdonald criteria divides response into 4 types of response based on imaging (MRI) and clinical features, as follows: 1) complete response (CR); 2) partial response (PR); 3) stable disease (SD); and 4) progression (PD).
Criteria:
CR: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions. No corticosteroids, clinically stable or improved.
PR: >=50% decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no new lesions. Stable or reduced corticosteroids, clinically stable or improved.
SD: does not qualify for complete response, partial response or progression. Clinically stable.
PD: >= 25% increase in enhancing lesions, any new lesions. Clinical deterioration.
Measured: every 8 weeks until disease progression, estimated 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2007 (estimated)
- Study startApr 2007
- Primary completionJun 2008
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- John D. Hainsworth, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00544817
- Sponsor's protocol ID
- SCRI CNS 09
- Status last verified
- Jul 2016
- First submitted
- 15 Oct 2007
- Last updated
- 1 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Hainsworth JD, Ervin T, Friedman E, Priego V, Murphy PB, Clark BL, Lamar RE. Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme. Cancer. 2010 Aug 1;116(15):3663-9. doi: 10.1002/cncr.25275.
PubMed 20564147
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Concurrent Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib in the First-Line Treatment of Patients With Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00544817
- Acronym / sponsor ID
- SCRI CNS 09
- Conditions
- Glioblastoma Multiforme
- Keywords
- Concurrent Radiation Therapy, Temozolomide, Sorafenib, First-line, Glioblastoma Multiforme, Phase II
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Apr 2007
- Primary completion
- Jun 2008 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 16 Oct 2007 (estimated)
- Results
- Posted 13 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The mechanism of action of sorafenib makes it an interesting drug to investigate in the treatment of patients with glioblastoma multiforme. Efficacy of agents with anti-angiogenic activity has already been demonstrated and the PDGF receptor target may also be pertinent in glioblastoma. The combination of temozolomide plus sorafenib has been investigated previously in the treatment of patients with advanced melanoma. The combination was generally well tolerated; in previously untreated patients, a standard dose of sorafenib (400mg PO bid) was administered with temozolomide 150mg/m2 PO daily for 5 days, repeated every 28 days (23).
In this multicenter phase II study, patients with newly diagnosed glioblastoma will receive standard treatment, including initial debulking surgical resection (if feasible) followed by high-dose radiation therapy with concurrent temozolomide. After completion of radiation therapy, patients will continue treatment with temozolomide (150mg/m2 days 1-5) and sorafenib (400mg PO bid daily), repeated at 28-day intervals for 6 cycles.
Detailed description
All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.
Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.
After completion of combined modality therapy, patients will have 4 weeks without any therapy.
Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be administered on days 1-28, repeated for 6 courses concurrently with temozolomide
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Experimental | Radiation: Radiation Therapy, Drug: Temozolomide, Drug: SorafenibIn the combined modality portion of the study, patients were administered: Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily Patients took a four week break before beginning follow-up systemic therapy: Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
- Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
- No previous treatment for glioblastoma except for previous surgical debulking (i.e. no previous radiotherapy, local chemotherapy, or systemic therapy).
- ECOG performance status 0 or 1 (See Appendix C)
- Age ≥ 18 years
Key exclusion criteria (16 listed)
- Patients must have the ability to swallow whole pills.
- Active cardiac disease: congestive heart failure > class 2 NYHA (Appendix D); unstable angina or new onset angina within the last 3 months; myocardial infarction within the last 6 months.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Uncontrolled hypertension defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optimal medical management
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection
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 |
|---|---|---|
| Radiation Therapy2 Gy/fraction, single daily fractions M-F, to 60 Gy total | Radiation | Combination Therapy |
| TemozolomideAlso: TemodarIn Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles | Drug | Combination Therapy |
| SorafenibAlso: NexavarIn follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months | Drug | Combination Therapy |
Primary outcome
Progression-free Survival
Time frame: 18 months
Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
2 secondary outcomes
Overall Survival
Time frame: 18 months
Objective Response
Time frame: every 8 weeks until disease progression, estimated 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20564147Hainsworth JD, Ervin T, Friedman E, Priego V, Murphy PB, Clark BL, Lamar RE. Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme. Cancer. 2010 Aug 1;116(15):3663-9. doi: 10.1002/cncr.25275.
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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.
John D. Hainsworth, M.D. study chair
SCRI Development Innovations, LLC
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiation Therapy, Temozolomide and Sorafenib in people with Glioblastoma Multiforme, run by SCRI Development Innovations, LLC at 10 sites in United States.
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 14 inclusion and 16 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 1 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival (time frame: 18 months). 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 NCT00544817, 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 1 Sep 2016.