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Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00544817
First received: October 15, 2007
Last updated: November 15, 2012
Last verified: November 2012

October 15, 2007
November 15, 2012
April 2007
June 2008   (final data collection date for primary outcome measure)
Progression-free Survival. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Feasibility, toxicity, efficacy, and be progression-free survival.
Complete list of historical versions of study NCT00544817 on ClinicalTrials.gov Archive Site
  • Overall Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Objective Response Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Overall survival and objective response rate
Not Provided
Not Provided
 
Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme
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.

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

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Glioblastoma Multiforme
  • Radiation: Radiation Therapy
    2 Gy/fraction, single daily fractions M-F, to 60 Gy total
  • Drug: Temozolomide

    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

    Other Name: Temodar
  • Drug: Sorafenib
    In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months
    Other Name: Nexavar
Experimental: Combination Therapy

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

Interventions:
  • Radiation: Radiation Therapy
  • Drug: Temozolomide
  • Drug: Sorafenib
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 May 11; [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
47
August 2010
June 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
  2. Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
  3. No previous treatment for glioblastoma except for previous surgical debulking (i.e. no previous radiotherapy, local chemotherapy, or systemic therapy).
  4. ECOG performance status 0 or 1 (See Appendix C)
  5. Age ≥ 18 years
  6. Adequate bone marrow function: hemoglobin ≥ 9.0g/dL; ANC ≥ 1500/μL; platelet count ≥ 100,000/μL.
  7. Adequate liver function

    • Total bilirubin ≤ 1.5 x ULN
    • ALT and AST ≤ 2.5 x ULN
  8. Serum creatinine < 1.5 x ULN
  9. 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.
  10. 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.
  11. 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.
  12. 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.

Exclusion Criteria:

  1. Patients must have the ability to swallow whole pills.
  2. 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.
  3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  4. Uncontrolled hypertension defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optimal medical management
  5. Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection
  6. Active clinically serious infection > grade 2
  7. Thrombotic or embolic events including cerebral vascular accident or TIAs within the past 6 months
  8. Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of the first dose of sorafenib
  9. Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of the first dose of sorafenib
  10. Serious non-healing wound, ulcer, or bone fracture
  11. Evidence or history of bleeding diathesis or coagulopathy
  12. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of beginning treatment with sorafenib
  13. Use of St. John's Wort or rifampicin
  14. Known or suspected allergy to sorafenib or temozolomide
  15. Any malabsorption problem
  16. Other active malignancies, or treatment for invasive cancer within the last 2 years
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00544817
SCRI CNS 09
No
SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
Bayer
Study Chair: John D. Hainsworth, M.D. SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP