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
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Radiation: Radiation Therapy
Drug: Temozolomide
Drug: Sorafenib
Phase 2

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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Progression-free Survival. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Objective Response Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: April 2007
Study Completion Date: August 2010
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00544817

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, South Carolina
Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
South Texas Oncology and Hematology
San Antonio, Texas, United States, 78258
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23235
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bayer
Investigators
Study Chair: John D. Hainsworth, M.D. SCRI Development Innovations, LLC
  More Information

Additional Information:
Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00544817     History of Changes
Other Study ID Numbers: SCRI CNS 09
Study First Received: October 15, 2007
Results First Received: November 15, 2012
Last Updated: November 15, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by SCRI Development Innovations, LLC:
Concurrent Radiation Therapy
Temozolomide
Sorafenib
First-line
Glioblastoma Multiforme
Phase II

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Sorafenib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014