Ph. 2 Sorafenib + Protracted Temozolomide in Recurrent GBM

NCT00597493 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00000464
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

PURPOSE AND OBJECTIVES: Primary Objective To evaluate the activity of Sorafenib plus protracted, daily temozolomide in patients with recurrent glioblastoma multiforme (GBM) as measured by 6-month PFS. Secondary Objectives To evaluate the safety and toxicity of combination therapy using Sorafenib plus temozolomide; To determine the pharmacokinetics of Sorafenib when combined with temozolomide in patients on and not on concurrent EIAC medications.

Conditions

Recurrent Glioblastoma Multiforme

Keywords

Recurrent Glioblastoma Multiforme; GBM; Glioblastoma; Sorafenib; Temozolomide; Brain Tumor; Recurrent GBM; Temodar; Gliosarcoma; Glioma; Nexavar

Outcome Measures

Primary Outcomes (1)

• 6 Month Progression Free Survival (PFS)

  Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.

  6 months

Secondary Outcomes (4)

• Safety and Toxicity of Combination

  16 months

• Pharmacokinetics: C-max

  13 months

• Pharmacokinetics: T-max

  13 months

• Pharmacokinetics: AUC-24

  13 months

Study Arms (1)

Sorafenib + Temozolomide

EXPERIMENTAL

Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changes in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure

Drug: Sorafenib and Temozolomide

Interventions

Sorafenib and Temozolomide DRUG

Temozolomide (50 mg per meter-squared of body surface area)every day by mouth in combination with sorafenib. Sorafenib will be taken by mouth twice every day. The dose of sorafenib will be 400 mg (2 x 200mg tablets).

Also known as: Temodar, Nexavar

Sorafenib + Temozolomide

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years.
• Pts must be presenting in 1st, 2nd or 3rd relapse. Prior therapy must have included external beam radiotherapy.
• Adequate bone marrow, liver and renal function as assessed by following:
• Hemoglobin \> 9.0 g/dl
• Absolute neutrophil ct (ANC) \> 1,500/mm3
• Platelet ct \> 100,000/mm3
• Total bilirubin \< 1.5 x ULN
• ALT \& AST \< 2.5 x ULN ( \< 5 x ULN for pts with liver involvement)
• INR \< 1.5 or PT/PTT within normal limits (unless on therapeutic anti-coagulation). Pts receiving anti-coagulation treatment with agent such as warfarin or heparin may be allowed to participate. For pts on warfarin, INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by local standard of care, until INR is stable.
• Creatinine \< 1.5 x ULN
• An interval of at least 2 weeks between prior surgical resection (1 week for biopsy)\& initiation of study regimen;
• An interval of at least 12 weeks from completion of standard, daily XRT, unless 1 of the following occurs: 1) new area of enhancement on MRI imaging that is outside XRT field; 2) biopsy proven recurrent tumor; 3) radiographic evidence of progressive tumor on 2 consecutive scans at least 4 weeks apart.
• An interval of at least 4 weeks from prior chemotherapy (except nitrosoureas which require 6 weeks) unless there is unequivocal evidence of tumor progression and pts has recovered from all anticipated toxicities from prior therapy.
• Karnofsky performance score \> 60%.
• Ability to understand and willingness to sign written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

You may not qualify if:

• Prior treatment with sorafenib.
• Significant cardiac disease including any of following: a) congestive heart failure \> class II NYHA; b) unstable angina (anginal symptoms at rest); c) new onset angina (within last 3 months); d) myocardial infarction within past 6 months; e) cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Known severe hypersensitivity to sorafenib or any of excipients or temozolomide.
• Excessive risk of bleeding as defined by stroke within prior 6 months, history of CNS or intraocular bleed, or septic endocarditis.
• Female pts who are pregnant/breast feeding, or adults of reproductive potential not employing effective method of birth control.
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in study such as uncontrolled diabetes, uncontrolled hypertension, active clinically serious infection \> CTCAE Grade 2, history of bleeding diathesis or coagulopathy, impairment of GI function or GI disease that may significantly alter absorption of the study regimen (i.e. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow tablets).
• Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks within past 6 months
• Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of 1st dose of study drug.
• Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of 1st dose of study drug.
• Serious non-healing wound, ulcer, or bone fracture.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of 1st study drug.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Pt is \< 3 years free of another primary malignancy except: if other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is basal cell skin cancer or cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Pts unwilling or unable to comply with protocol including ability to swallow whole pills or presence of any malabsorption syndrome.
• Concurrent administration of St. John's Wort.

Sponsors & Collaborators

• Duke University: lead
• Bayer: collaborator
• Schering-Plough: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Reardon DA, Vredenburgh JJ, Desjardins A, Peters K, Gururangan S, Sampson JH, Marcello J, Herndon JE 2nd, McLendon RE, Janney D, Friedman AH, Bigner DD, Friedman HS. Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol. 2011 Jan;101(1):57-66. doi: 10.1007/s11060-010-0217-6. Epub 2010 May 5.

  PMID: 20443129 RESULT

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Gliosarcoma; Glioma

Interventions

Sorafenib; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: David Reardon, MD
• Organization: Duke University Health System

David_Reardon@DFCI.harvard.edu

617-632-2166

Study Officials

• David A Reardon, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 9, 2008
• First Posted: January 18, 2008
• Study Start: September 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: December 1, 2010
• Last Updated: June 24, 2013
• Results First Posted: June 24, 2013

Record last verified: 2013-05

Locations

US (1)