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Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma

Study Purpose

This phase II trial studies how well dovitinib works in treating patients with recurrent or progressive glioblastoma. Dovitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Histologically confirmed glioblastoma, recurrent after standard external-beam fractionated radiotherapy and temozolomide chemotherapy.
  • - Patients who have NOT received any anti-angiogenic therapy (Anti-VEGF, including avastin, cediranib, or other anti-angiogenic therapies like cilengitide) on Anti-angiogenic Therapy Naive Patients Arm.
No more than two recurrences are allowed on Anti-angiogenic Therapy Naive Patients Arm.
  • - Patients who have received any anti-angiogenic therapy (Anti-VEGF, including avastin, cediranib, or other anti-angiogenic therapies like cilengitide) on Anti-angiogenic Therapy Patients Arm.
Any number of recurrences are allowed on Anti-angiogenic Therapy Patients Arm.
  • - Karnofsky performance status ≥ 60% - Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.
  • - Platelets ≥ 100 x 10^9/L.
  • - Hemoglobin (Hgb) > 9 g/dL.
  • - Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN.
  • - Serum creatinine ≤ 1.5 x ULN.
  • - Minimum interval since completion of radiation treatment is 12 weeks.
  • - Minimum interval since last drug therapy 2 weeks since last non-cytotoxic therapy 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.
  • - Patients must be able to provide written informed consent.
  • - Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant; female patients of child-bearing potential must have a negative pregnancy test.
  • - Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission; patients with other prior malignancies must be disease-free for ≥ three years.
  • - Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment and/or for at least 5 days before starting treatment.

Exclusion Criteria:

  • - Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
  • - Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months.
  • - Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: - Impaired cardiac function or clinically significant cardiac diseases, including any of the following: - History or presence of serious uncontrolled ventricular arrhythmias.
  • - Clinically significant resting bradycardia.
  • - Left ventricular ejection fraction (LVEF) assessed by 2-dimensional (2-D) echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multi gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is higher) - Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), and transient ischemic attack (TIA) - Uncontrolled hypertension defined by a systolic blood pressure (SBP) ≥ 160 mm Hg and/or diastolic blood pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication(s) - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) - Cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
  • - Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) - Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • - Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception; highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 8 weeks after the end of study treatment; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study treatment.
  • - Fertile males not willing to use contraception, as stated above.
  • - Patients who are currently receiving full dose anticoagulation treatment with therapeutic doses of warfarin or anti-platelet therapy (e.g., Plavix [clopidogrel bisulfate]); treatment with locally accepted low molecular weight heparin and low dose of acetylsalicylic acid (i.e., 81mg or 100 mg daily) to prevent cardiovascular events or strokes is allowed.
  • - Patients unwilling or unable to comply with the protocol.
  • - Any significant hemorrhage defined as > 1 cm diameter of blood seen on the MRI or CT scan.
If > 1 cm of acute blood is detected, the patient will be ineligible for this trial.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01753713
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Manmeet Ahluwalia, MD
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Manmeet Ahluwalia
Principal Investigator Affiliation Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Additional Details

PRIMARY OBJECTIVES: Anti-angiogenic Therapy Naive Patients: To determine 6 month progression-free survival (PFS6) in anti-angiogenic therapy (including anti-vascular endothelial growth factor (VEGF) therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM) in patients treated with dovitinib.Anti-angiogenic Therapy Patients: To estimate time to progression in patients with recurrent or progressive Glioblastoma who have progressed on anti-angiogenic therapy (including anti-VEGF therapy). SECONDARY OBJECTIVES: 1. To evaluate the side effect profile of dovitinib in both patient populations. 2. To evaluate the efficacy of dovitinib as measured by objective response rate (ORR) in both patient populations. 3. To estimate time to percentage of patients free from progression at 6 months (PFS-6)in patients with recurrent or progressive Glioblastoma who have progressed on antiangiogenic therapy (including anti-VEGF therapy). (Anti-angiogenic Therapy Patients) 4. To estimate time to progression in anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naiVe patients with recurrent glioblastoma (GBM) in patients treated with dovitinib. (Anti-angiogenic Therapy Naive Patients) 5. To evaluate the overall survival (OS) in both patient populations. EXPLORATORY OBJECTIVES: To explore association between clinical outcome and potential biomarkers that may include microparticles, PlGF, PDGF-AA, PDGF-AB, PDGF-BB, SDF-1a, thrombospondin-1, Ang1, and Il-6, IL-8 and FGF. OUTLINE: Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.

Arms & Interventions

Arms

Experimental: Anti-angiogenic Therapy Naive Patients

Patients who have progressed without anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Experimental: Anti-angiogenic Therapy Patients

Patients who have progressed on anti-angiogenic therapy. Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - dovitinib

Given PO

Other: - laboratory biomarker analysis

Correlative studies

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Cleveland, Ohio

Status

Address

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195