Phase I Portion of Phase I/II Sorafenib With Radiation and Temozolomide in Newly Diagnosed Glioblastoma or Gliosarcoma

NCT00734526 | Terminated Phase 1

• 2 other identifiers: 2008-0059NCI-2012-01617
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of sorafenib that can be given in combination with temozolomide. The safety of this combination will also be studied.

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; Brain Cancer; Sorafenib; Temozolomide; Radiation; Radiotherapy; XRT

Outcome Measures

Primary Outcomes (2)

• Phase I: Sorafenib Maximum Tolerated Dose (MTD)

  MTD of sorafenib given during (concurrently with) external beam radiation therapy and daily temozolomide (75mg/m\^2), and with standard dose temozolomide (150-200mg/m\^2 5 days out of 28) after radiation therapy (adjuvant) in patients with newly diagnosed glioblastoma or gliosarcoma MTD is defined as the dose level below which there were 2 or more participants out of 6 with Dose-limiting toxicities (DLTs). by the conclusion of the first cycle of post-radiation therapy (14 weeks),

  4 Week Cycles

• Second MTD

  maximum tolerated dose (MTD) of sorafenib given during (concurrently with) external beam radiation therapy and daily temozolomide (75mg/m2), and with dose dense temozolomide (100mg/m2 21 days out of 28) after radiation therapy (adjuvant) in patients with newly diagnosed glioblastoma or gliosarcoma

  4 weeks

Secondary Outcomes (1)

• Phase II: Time to Progression

  15 Months or till progressive disease, severe toxicity or death.

Study Arms (4)

Dose Level 1

EXPERIMENTAL

Temozolomide + Radiation, Followed by Higher Dose Temozolomide in a Shorter Cycle Temozolomide 75mg/m\^2 daily during radiation therapy, and 150mg/m\^2 in the first cycle of adjuvant therapy. Dose Level 1 will receive sorafenib in the adjuvant phase (following radiation therapy) at the dose of 400mg BID in combination with standard dose temozolomide 150-200 mg/m\^2 two days out of 28 day cycle. Radiotherapy 2.0 Grey (Gy)/day given daily 5 days per week for total of 60.0 Gy over 6 weeks.

Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib

2

EXPERIMENTAL

Temozolomide + Lower Dose Sorafenib + Radiation, Followed by Higher Dose Temozolomide in a Shorter Cycle + Higher Dose Sorafenib

Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib

3

EXPERIMENTAL

Temozolomide + Lower Dose Sorafenib + Radiation, Followed by Lower Dose Temozolomide in a Longer Cycle + Lower Dose Sorafenib

Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib

4

EXPERIMENTAL

Temozolomide + Higher Dose Sorafenib + Radiation, Followed by Lower Dose Temozolomide in a Longer Cycle + Higher Dose Sorafenib

Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib

Interventions

Temozolomide DRUG

Groups 1 \& 2: 75 mg/m\^2 Once Daily by Mouth During Radiation; 4 Weeks after Completion of Radiation, 150-200 mg/m\^2 Once Daily by Mouth Days 1-5 of 1st 28-Day Cycle, then 75 mg/m\^2 Once Daily by Mouth Days 1-5 for Subsequent 28-Day Cycles. Groups 3 \& 4: 75 mg/m\^2 Once Daily by Mouth During Radiation; 4 Weeks after Completion of Radiation, 75-100 mg/m\^2 Once Daily by Mouth Days 1-21 every 28-Day Cycle.

2; 3; 4; Dose Level 1

Radiation RADIATION

Total of 60 Gy delivered over 30 Days (approximately 6 weeks).

Also known as: Radiotherapy, XRT

2; 3; 4; Dose Level 1

Sorafenib DRUG

Group 1: 4 Weeks after Completion of Radiation, 400 mg Twice Daily by Mouth. Group 2: 200 mg Twice Daily by Mouth during Radiation; 4 Weeks after Completion of Radiation, 400 mg Twice Daily by Mouth. Group 3: 200 mg Twice Daily by Mouth during Radiation; 4 Weeks after Completion of Radiation, 200 mg Twice Daily by Mouth. Group 4: 400 mg Twice Daily by Mouth during Radiation; 4 Weeks after Completion of Radiation, 400 mg Twice Daily by Mouth.

Also known as: BAY43-9006

2; 3; 4; Dose Level 1

Eligibility Criteria

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

You may qualify if:

• Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis.
• Patients must have at least 1 block of tumor tissue available for submission to the central pathologist for analysis of gene expression status by QRT-PCR; there must be at least 1 cm\^2 of tumor from the block when cut on a slide: fresh frozen tumor tissue acquisition is also encouraged, but not required. Unstained slide submission without a block submission is not acceptable for study entry.
• Diagnosis must be established by open biopsy or tumor resection. Patients who have only had a stereotactic biopsy are not eligible..
• The tumor must have a supratentorial component.
• Patients must have recovered from the effects of surgery, postoperative infection, and other complications before study registration.
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
• A diagnostic contrast-enhanced MRI or CT scan (if MRI is contraindicated) of the brain must be performed postoperatively in the period between surgery and initiation of radiation therapy.
• Therapy must begin \</=5 weeks after the most recent brain tumor surgery.
• History/physical examination within 14 days prior to study registration.
• Neurologic examination within 14 days prior to study registration.
• Documentation of steroid doses within 14 days prior to study registration and stable or decreasing steroid dose within 5 days prior to registration.
• Karnofsky performance status of \>/= 60.
• Age \>/= 18 years.
• Patients with well-controlled hypertension are eligible (systolic blood pressure of \</= 140 mgHg or diastolic pressure \</= 90 mgHg).
• Complete blood count (CBC)/differential obtained within 14 days prior to study registration, with adequate bone marrow function as defined below: Absolute neutrophil count (ANC) \>/= 1500 cells/mm\^3; Platelets \>/= 100,000 cells/mm\^3;Hemoglobin \>/= 10 g/dl.

You may not qualify if:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for \>/= 3 years.
• Recurrent or multifocal malignant gliomas
• Metastases detected below the tentorium or beyond the cranial vault.
• Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable.
• Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
• Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
• Severe, active co-morbidity, defined as follows: Cardiac disease - Congestive heart failure \> class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Hepatitis B or C infection;
• (7. continued) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
• (7. continued) Known history or symptoms and laboratory results consistent with Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition (note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive); Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy;
• (7. continued) Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity; Arterial thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months; Pulmonary hemorrhage/bleeding event \> Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 within 4 weeks of first dose of study drug;
• (7. continued) Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of first dose of study drug; Serious non-healing wound, ulcer, or bone fracture; Evidence or history of bleeding diathesis or coagulopathy
• Uncontrolled hypertension defined as systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Use of St. John's Wort or rifampin (rifampicin).
• No tissue provided for histopathologic review and QRT-PCR analysis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Temozolomide; Radiation; Radiotherapy; 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; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Vinay K. Puduvalli, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2008
• First Posted: August 14, 2008
• Study Start: December 18, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: November 9, 2018

Record last verified: 2018-11

Locations

US (1)