AzTrials
AzTrials

GlioblastomaPhase 2NCT01817751

Sorafenib, Valproic Acid, and Sildenafil in Treating Patients With Recurrent High-Grade Glioma

A Phase 2 study testing sorafenib tosylate, valproic acid and sildenafil citrate in people with Glioblastoma and Recurrent Adult Brain Neoplasm, run by Virginia Commonwealth University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this research study is to test the safety, tolerability, and effectiveness of the combination of three drugs, sorafenib (Nexavar®), valproic acid (Depakote®), and sildenafil (Viagra®), when used to treat high-grade glioma, a type of brain tumor. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sorafenib tosylate, valproic acid and sildenafil citrate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
1 siteUnited States
Study dates
11 Apr 2013to 12 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologically confirmed high-grade glioma (World Health Organization (WHO) grade 3 or 4), with documented computed tomography (CT) or magnetic resonance imaging (MRI) progression or recurrence. Biopsy is also an acceptable method of confirming progression or recurrence. If initial tumor was grade 2 glioma, histological confirmation of high-grade recurrence is required
  • After first interim analysis, if the study proceeds to enrollment of selected patients (only those who have platelet-derived growth factor receptor (PDGFRa)-positive tumors), patients will be pre-registered for PDGFRa analysis and registered to the combination treatment schema only if PDGFRa-positive an all other enrollment criteria are met.
  • Measurable or evaluable disease by response assessment in neuro-oncology (RANO) (MRI) or MacDonald (CT) criteria
  • Fixed or decreasing dose of corticosteroids (or no corticosteroids) for at least 1 week prior to cycle 1 day 1.
  • At least 12 weeks since the completion of radiation therapy to a total of >=50 Gray (Gy).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Show all 16Show fewer
  • White blood cell (WBC) >= 3,000/mm^3
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin (Hgb) >= 8.5 g/dL
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) for the laboratory
  • Total bilirubin =< 1.5 x ULN for the laboratory (total bilirubin criteria may be waived if a patient has documented Gilbert's disease)
  • Creatinine clearance (CrCL) >= 30 mL/min as calculated by standard Cockcroft-Gault equation
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
  • Women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation and for 2 months following completion of study treatment.
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Investigational agent within 4 weeks of first dose of study treatment
  • Prior bevacizumab or tyrosine-kinase inhibitor
  • History of allergic reactions or intolerance to any of the required agents on the study
  • Any condition that would prohibit patient from initiating valproic acid. Current or prior valproic acid treatment is allowed (do not need to be ≥ LLN for laboratory for enrollment).
  • Seizure disorder necessitating the use of enzyme-inducing antiepileptic drugs (EIAEDs). Efforts may be made by the treating physician to change the antiepileptic drug from another agent to valproic acid or non-EIAED prior to excluding the patient from study
  • Contraindication to antiangiogenic agents, including:
Show all 33Show fewer
  • Bronchopulmonary hemorrhage/bleeding event >= grade 2 (NCI Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) within 4 weeks or less prior to first dose of study drug
  • Any other hemorrhage/bleeding event >= grade 3 (NCI CTCAE v4.0) within 4 weeks or less prior to first dose of study treatment
  • Radiological evidence of any intracranial hemorrhage within the 4 weeks or less less prior to first dose of study treatment
  • History of significant intratumoral, intracerebral, or subarachnoid hemorrhage
  • Serious non-healing wound, ulcer, or bone fracture
  • Documented bowel perforation within 6 months of the start of study treatment.
  • Major surgery within 2 weeks of the start of study treatment, or ongoing complications from surgeries performed previously
  • Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or higher, ventricular arrhythmias requiring antiarrhythmic therapy, recent (within 6 months) myocardial infarction or unstable coronary artery disease.
  • Systolic blood pressure (BP) > 160 mm Hg or diastolic pressure > 100 mm Hg despite optimal medical management
  • History of priapism
  • Known history of retinitis pigmentosa
  • Known mitochondrial disorder caused by mutations in mitochondrial DNA polymerase γ.
  • Arterial thromboembolic or embolic events such as myocardial infarction, cerebrovascular accident, including transient ischemic attacks 6 months prior to first study treatment
  • Serious uncontrolled infection > grade 2 (CTCAE v 4)
  • Known human immunodeficiency virus (HIV) positivity
  • Unable to swallow medication or suspected malabsorption
  • Patients on chronic nitrate therapy or alpha-blockers
  • Exclude persons who require ongoing administration of STRONG CYP3A4 inhibitors and/or STRONG CYP3A4 inducers and/or STRONG CYP2C9 inhibitors.
  • Women who are pregnant or nursing
  • Persistent heart rate (HR) <50 or >120 beats per minute (bpm)
  • Corrected QT (QTc) > 480 ms (grade 2 or greater) on screening electrocardiogram (ECG)
  • If baseline QTc on screening ECG meets exclusion criteria on screening assessment:
  • Check potassium and magnesium levels
  • Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc
  • For patients with a heart rate (HR) 60-100 bpm, no manual read of QT is required
  • For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required using Fridericia correction
  • Other condition(s) that in the opinion of the investigator might compromise the objectives of the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

Other trials in United States

About this study

Official title: Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma

The purpose of this research study is to test the safety, tolerability, and effectiveness of the combination of three drugs, sorafenib (Nexavar®), valproic acid (Depakote®), and sildenafil (Viagra®), when used to treat high-grade glioma, a type of brain tumor.

Read the detailed description

The study is a single-center, open-label phase 2 study, with an early stopping rule in place for safety. The trial will include patients with recurrent or progressive high-grade glioma.

The trial will be conducted in an adaptive design, with a Simon's mini-max 2-stage design incorporating an interim analysis for efficacy

Being tested
sorafenib tosylate, valproic acid, sildenafil citrate
Keywords
central nervous system, Brain and Nervous System
Medical subject headings
Glioblastoma, Brain Neoplasms, Glioma, Neurologic Manifestations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sorafenib tosylateDrug

    Also called pyridinecarboxamide, chloro-trifluoromethylphenyl pyridine-carboxylic acid methylamide-methylbenzenesulfonate tosylate, Nexavar

    Given by mouth

  • valproic acidDrug

    Also called 2-Propylpentanoic or Propylvaleric Acid, Alti-Valproic, Depakene, Di-n-propylacetic Acid, Ergenyl, Novo-Valproic, VA, Valproate, Valproate Sodium

    Given by mouth

  • sildenafil citrateDrug

    Also called Viagra

    Given by mouth

Study groups in NCT01817751
Study groupRoleWhat they receive
Treatment (sorafenib tosylate, valproic acid, sildenafil)Experimental* Sorafenib 400 mg orally twice a day; * Valproic acid (to levels ≥ Lower Level of Normal (LLN) orally twice a day; * Sildenafil 50 mg orally twice a day A cycle consists of 4 weeks. *The first 6 patients evaluable for qualifying toxicity assessment will be treated as a safety lead-in; enrollment will be gated (the first 3 evaluable patients must complete 4 weeks of the combination therapy before the next 3 patients start combination treatment on protocol)
Receives: Drug: sorafenib tosylate; Drug: valproic acid; Drug: sildenafil citrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With 6-Month Progression Free Survival (PFS)

    Number of patients evaluable for response, regardless of tumor platelet derived growth factor receptor (PDGFR) status, with 6- month PFS defined as the time from the first day a patient receives study treatment until time of progression per response assessment in neuro-oncology (RANO) or Macdonald criteria or death, whichever occurs first.

    Measured: Up to 6 months

Secondary outcomes (6)

  1. Number of Participants Whose Tumors Express PDGFRa With and Without 6-Month PFS.

    Number of patients evaluable for response, with tumors that express PDGFRα, with 6-month PFS defined as the time from the first day a patient receives study treatment until time of progression per RANO or Macdonald criteria or death, whichever occurs first.

    Measured: Up to 6 months

  2. Number of Participants With Best Response of CR Plus Number of Participants With Best Response of PR.

    Overall response rate (CR+PR), using RANO or Macdonald criteria, in patients evaluable for response regardless of tumor PDGFR status

    Measured: From the first day of study treatment until best response or off study, up to 4 years

  3. Number of Participants Whose Tumors Express PDGFRa With Best Response of CR Plus Number of Participants Whose Tumor Expresses PDGFRa With Best Response of PR.

    Overall response rate (CR+PR), using RANO or Macdonald criteria, in patients who are evaluable for response and who have tumors that express PDGFRα.

    Measured: From initiation of study treatment to time of best response or off-study (up to 4 years)

  4. Number of Participants With 12-Month Overall Survival (OS)

    Number of patients evaluable for response, regardless of tumor PDGFR status, who are alive at 12 months after the first day a patient receives study treatment. Overall Survival (OS) defined as the time from the first day a patient receives study treatment until death by any cause.

    Measured: 12 months

  5. Number of Participants Whose Tumors Express PDGFRa With and Without 12-Month OS.

    Number of patients evaluable for response with tumors that express PDGFRα who are alive at 12 months after the first day a patient receives study treatment. On study is defined as the time from the first day a patient receives study treatment until death by any cause.

    Measured: Up to 12 months

  6. Evaluation of Safety and Toxicity of Sorafenib, Valproic Acid, and Sildenafil

    Number of patients with adverse events

    Measured: From initiation of study therapy to completion of adverse event (AE) observation period, up to 30 days following the end of study treatment, up to 7 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2013 (estimated)
  2. Study start11 Apr 2013
  3. Primary completion27 Aug 2020
  4. Study completion12 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01817751
Sponsor's protocol ID
MCC-14816
Other IDs
HM14816, NCI-2013-00705, P30CA016059
Status last verified
Jun 2024
First submitted
20 Mar 2013
Last updated
17 Jul 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.

    PubMed 34171339

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sorafenib tosylate, valproic acid and sildenafil citrate in people with Glioblastoma and Recurrent Adult Brain Neoplasm, run by Virginia Commonwealth University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With 6-Month Progression Free Survival (PFS) (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01817751, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in