Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma

NCT01753713 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CASE4312NCI-2012-02284
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (2)

• Arm 1: Progression Free Survival (PFS)

  Number of anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM). The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6. Progression is defined using the Response Assessment in Neuro-Oncology (RANO) Criteria where CR = Total disappearance of lesions, PR = \>50% reduction in lesions and SD = \<25% reduction in lesions

  6 months

• Arm 2: Determine Median Time to Progression

  Anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) patients with recurrent glioblastoma (GBM). Time to tumor progression (TTP), is defined as the time from randomization to time of progressive disease. So it is ongoing and will be assessed every 8 weeks …8, 16, 24, 32 …week. Progression is defined as \>25% increase in size of lesions or evidence of new lesions

  From randomization to time of progression every 8 weeks (2 cycles of treatment) up to 32 weeks

Secondary Outcomes (4)

• Toxicity Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

  Assessed until 30 days after treatment up to 32 weeks

• Objective Response Rate Using Modified Revised Assessment in Neuro-Oncology (RANO) Criteria

  Up to 30 days after treatment

• Median Progression Free Survival

  6 months

• Overall Survival

  to death, approximately 2 years

Other Outcomes (1)

• Changes From Baseline in Circulating Growth Factors and Soluble Receptors.

  Up to 30 days after treatment

Study Arms (2)

Anti-angiogenic Therapy Naive Patients

EXPERIMENTAL

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.

Drug: dovitinib; Other: laboratory biomarker analysis

Anti-angiogenic Therapy Patients

EXPERIMENTAL

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.

Drug: dovitinib; Other: laboratory biomarker analysis

Interventions

dovitinib DRUG

Given PO

Also known as: CHIR-258, receptor tyrosine kinase (RTK) inhibitor TKI258, RTK inhibitor TKI258, TKI258

Anti-angiogenic Therapy Naive Patients; Anti-angiogenic Therapy Patients

laboratory biomarker analysis OTHER

Correlative studies

Anti-angiogenic Therapy Naive Patients; Anti-angiogenic Therapy Patients

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Manmeet Ahluwalia, MD: lead
• National Cancer Institute (NCI): collaborator
• Novartis: collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Receptor Protein-Tyrosine Kinases

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)

Protein-Tyrosine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Manmeet Ahluwalia, MD
• Organization: Case Comprehensive Cancer Center

ahluwam@ccf.org

216-844-5060

Study Officials

• Manmeet Ahluwalia

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: December 20, 2012
• Study Start: December 20, 2012
• Primary Completion: January 28, 2015
• Study Completion: September 20, 2017
• Last Updated: December 12, 2017
• Results First Posted: August 8, 2017

Record last verified: 2017-10

Locations

US (1)