Sunitinib to Treat Recurrent Brain Cancer

NCT00923117 | Terminated Phase 2 Results DMC

• 2 other identifiers: 08016808-C-0168
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

Background: One way tumors are able to grow is by forming new blood vessels that supply them with nutrients and oxygen. Sunitinib blocks certain proteins on the surface of tumor and blood vessel cells that are involved with the formation of new blood vessels. Blocking these proteins may prevent the tumor cells or blood vessels from continuing to grow. Objectives: To determine whether sunitinib can cause tumors to shrink or stabilize in patients with recurrent brain cancer. Eligibility: Patients 18 years of age or older with brain cancer whose disease has worsened after standard treatment with surgery, radiation. Design: Patients take a sunitinib pill once a day in 4-week treatment cycles. Treatment may continue as long as the tumor remains stable or decreases in size and the side effects of treatment are tolerated. Routine blood tests are done every 2 weeks during the first 8 weeks of treatment and then every 4 weeks after that. Magnetic resonance imaging (MRI) scans are done before starting treatment (at baseline) and at the end of every 4-week cycle to monitor tumor growth. Positron emission tomography (PET) scans are done at baseline and at the end of the first cycle. Neurological and physical examinations are done at baseline, at week 2 of treatment and at the end of every treatment cycle. Health-related quality of life is assessed every 4 weeks. Pregnancy tests, electrocardiograms and echocardiograms are repeated as needed.

Conditions

Glioblastoma Multiforme; Malignant Gliomas; Anaplastic Gliomas

Keywords

Glioblastoma; Chemotherapy; Anti-Angiogenesis; Radiation; Brain Tumor; Malignant Glioma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• 6-month Progression-free Survival.

  Time between the start of treatment to progression. Progression is defined by the RANO(Response Assessment in Neuro-Oncology) criteria. Progression is defined by any of the following: 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.

  6 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  7/2/08 -12/6/13

Study Arms (2)

Bevacizumab resistant patients

EXPERIMENTAL

Patients who had tumor progression while treated with bevacizumab.

Drug: Sutent (sunitinib)

Bevacizumab naive patients

EXPERIMENTAL

Patients with progressive tumor who have not been treated with bevacizumab.

Drug: Sutent (sunitinib)

Interventions

Sutent (sunitinib) DRUG

Oral dose 37.5 mg daily on a continuous 4 week cycle

Bevacizumab naive patients; Bevacizumab resistant patients

Eligibility Criteria

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

You may qualify if:

• Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant gliomas include glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).
• Patients may have received prior therapy with bevacizumab, but not within six weeks of starting treatment with sunitinib. Patients who received prior therapy with bevacizumab must have demonstrated radiographic disease progression while being treated with bevacizumab.
• Patients must have progressed after radiation and temozolomide therapy and have an interval of greater than or equal to 4 weeks from the completion of radiation therapy to study entry. If the patient has had prior stereotactic radio surgery, true tumor progression must be corroborated by fludeoxyglucose 18F (FDG)-positron emission tomography (PET) or magnetic resonance (MR) spectroscopy imaging.
• Patients must have evidence of tumor progression by contrast enhanced perfusion magnetic resonance imaging (MRI) or computed tomography (CT) scan. This scan should be performed within 14 days prior to registration and on a five-day stable dose of steroids. If the steroid dose is increased between the date of imaging and registration, a new baseline MR/CT is required. The same type of scan (i.e., MRI or CT) must be used throughout the period of protocol treatment for tumor measurement.
• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
• They have recovered from the effects of surgery.
• Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/MRI should be done:
• no later than 96 hours in the immediate post-operative period, or
• at least 4 weeks post-operatively, and
• within 14 days of registration, and
• on a steroid dosage that has been stable for at least 5 days.
• f) Normal organ and marrow function defined as: total leukocyte count greater than or equal to 3000 cells/ul, absolute neutrophil count (ANC) greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times the upper limit of normal, and bilirubin less than or equal to 1.5 times the upper limit of normal, hemoglobin greater than or equal to 9.0 g/dL , serum calcium less than or equal to 12.0 mg/dL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to 1.5 times the upper limit of normal, prothrombin time (PT) less than or equal to 1.5 upper limits of normal (ULN). Eligibility level for hemoglobin may be reached by transfusion.
• g) The effects of sunitinib on the developing human fetus at the recommended therapeutic dose are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• h) All patients or their previously designated durable power of attorney (DPA) (if the patient is deemed by the treating physician to be impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study.
• i) Patients must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks.

You may not qualify if:

• Patients who, in the view of the treating physician, have significant active cardiac, hepatic, renal, or psychiatric diseases are ineligible.
• Patients with a history of prior therapy directed against vascular endothelial growth factor (VEGF) (e.g. sorafenib, pazopanib, Zactima (ZD6474), AZD2171), with the exception of bevacizumab, will not be allowed to enroll.
• Concurrent use of other standard chemotherapeutics or investigative agents.
• Patients known to have a malignancy (other than their malignant glioma) that has required treatment in the last 12 months and/or are expected to require treatment in the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the cervix).
• Patients who have an active infection.
• Pregnant (positive pregnancy test) or nursing women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 3 months after the completion of sunitinib therapy.
• Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal anti-inflammatory agents, cyclooxygenase -2 (COX-2) inhibitors).
• Serious or non-healing wound, ulcer or bone fracture
• History of any of the following within 6 months of study entry: abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, stroke, myocardial infarction or unstable angina. Patients will not undergo diagnostic screening for any of these conditions.
• Invasive procedures defined as follows:
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
• Anticipation of need for major surgical procedures during the course of the study
• Core biopsy within 7 days prior to start of therapy
• Uncontrolled hypertension (greater than 150/100 mmHg) while on antihypertensive medications.
• New York Heart Association class II or greater congestive heart failure.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

  PMID: 17237035 BACKGROUND

• Prados MD, Schold SC Jr, Fine HA, Jaeckle K, Hochberg F, Mechtler L, Fetell MR, Phuphanich S, Feun L, Janus TJ, Ford K, Graney W. A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro Oncol. 2003 Apr;5(2):96-103. doi: 10.1093/neuonc/5.2.96.

  PMID: 12672281 BACKGROUND

• Prados MD, Warnick RE, Mack EE, Chandler KL, Rabbitt J, Page M, Malec M. Intravenous carboplatin for recurrent gliomas. A dose-escalating phase II trial. Am J Clin Oncol. 1996 Dec;19(6):609-12. doi: 10.1097/00000421-199612000-00016.

  PMID: 8931682 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Interventions

Sunitinib

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)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The study was terminated based on results of an interim analysis for futility.

Results Point of Contact

• Title: Dr. Teri Kreisl
• Organization: National Cancer Institute, National Institutes of Health

kreislt@mail.nih.gov

301-402-3423

Study Officials

• Teri N Kreisl, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: June 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: September 30, 2015
• Results First Posted: June 25, 2013

Record last verified: 2014-07

Locations

US (1)