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

NCT00544817 | Completed Phase 2 Results

• 1 other identifier: SCRI CNS 09
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 10

Brief 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. 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.

Conditions

Glioblastoma Multiforme

Keywords

Concurrent Radiation Therapy; Temozolomide; Sorafenib; First-line; Glioblastoma Multiforme; Phase II

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.

  18 months

Secondary Outcomes (2)

• Overall Survival

  18 months

• Objective Response

  every 8 weeks until disease progression, estimated 18 months

Study Arms (1)

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

Radiation: Radiation Therapy; Drug: Temozolomide; Drug: Sorafenib

Interventions

Radiation Therapy RADIATION

2 Gy/fraction, single daily fractions M-F, to 60 Gy total

Combination Therapy

Temozolomide DRUG

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

Also known as: Temodar

Combination Therapy

Sorafenib DRUG

In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months

Also known as: Nexavar

Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Bayer: collaborator

Study Sites (10)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Spartanburg Regional Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

South Texas Oncology and Hematology

San Antonio, Texas, 78258, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23235, United States

Location

Related Publications (1)

• 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.

  PMID: 20564147 RESULT

MeSH Terms

Conditions

Glioblastoma

Interventions

Radiotherapy; Temozolomide; Sorafenib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

ASKSARAH@scresearch.net

877-691-7274

Study Officials

• John D. Hainsworth, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2007
• First Posted: October 16, 2007
• Study Start: April 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: August 1, 2010
• Last Updated: September 1, 2016
• Results First Posted: December 13, 2012

Record last verified: 2016-07

Locations

US (10)