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New treatment option for Intracranial Meningioma
Official title Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
ClinicalTrials.gov ID: NCT02523014
What this study is testing
What is Vismodegib?
Vismodegib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for intracranial meningioma.
Also referred to as GDC-0449.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase II trial studies how well vismodegib, focal adhesion kinase (FAK) inhibitor GSK2256098, and capivasertib work in treating patients with meningioma that is growing, spreading, or getting worse (progressive). Vismodegib, FAK inhibitor GSK2256098, capivasertib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Documentation of disease:
- Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
- Molecular documentation: Presence of SMO, PTCH1, NF2, CDKN2A, AKT1, PIK3CA, PTEN mutations, CDKN2A copy number loss, CDK4, CDK6, CCND1, CCND2, CCND3...
- Progressive OR residual disease, as defined by the following:
- Residual measurable disease: residual measurable disease immediately after surgery without requirement for progression; for grade I disease...
See the full eligibility criteria
Who can join
- Documentation of disease:
- Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
- Molecular documentation: Presence of SMO, PTCH1, NF2, CDKN2A, AKT1, PIK3CA, PTEN mutations, CDKN2A copy number loss, CDK4, CDK6, CCND1, CCND2, CCND3, or CCNE1 copy number gain in tumor sample as documented specifically...
- Progressive OR residual disease, as defined by the following:
- Residual measurable disease: residual measurable disease immediately after surgery without requirement for progression; for grade I disease, progression pre-operatively needs to be documented, with an increase in size...
- Progressive measurable disease: progression defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than...
- Post radiation patients: patients with measurable and progressive meningioma who have received radiation are potentially eligible, but need to show evidence of progressive disease after completion of radiation; if the...
- Measurable disease: measurable disease is defined by a bidimensionally measurable main lesion on MRI or computed tomography (CT) images (MRI preferred) with clearly defined margins and a minimum diameter of 10 mm in...
- Prior treatment
- Prior medical therapy is allowed but not required
- No limit on number of prior therapies
- No chemotherapy, or other investigational agents within 28 days prior to registration
- No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study; additionally, no cases of nitrosourea or mitomycin C within 6 weeks prior to registration
- For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval \> 4 weeks must have elapsed from completion of radiation therapy to registration; if the progressive lesion is...
- Steroid dosing stable for at least 4 days
- Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue
- No craniotomy 28 days prior to and after registration
- Not pregnant and not nursing: \ A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least...
- For patients with NF2/CDKN2A/AKT1/PIK3CA/PTEN mutation, CKDN2A copy number loss, or CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1 copy number gain: Age \>= 18 years
- For patients with SMO/PTCH1 mutation: Age \>= 30 years
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- Patient history:
- Patients with history of neurofibromatosis (NF) may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months
- No metastatic meningiomas (as defined by extracranial meningiomas outside of CNS) allowed; spinal meningiomas are allowed
- No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug
- No known active hepatitis B or C
- No current Child Pugh class B or C liver disease
- No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)
- No uncontrolled hypertension defined as blood pressure (BP) \> 140/90
- No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration
- No major surgery within 28 days prior to registration for any patients with AKT1/PIK3CA/PTEN mutations receiving capivasertib
- For patients going on to receive capivasertib (i.e. enrolled after Update #08)
- Patients should not have any of the following cardiac criteria:
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram (EKG) (e.g., complete left bundle branch block, third degree heart block)
- Any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for Torsade de Pointes, congenital long QT syndrome, family history of...
- Experience any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York...
- Uncontrolled hypertension (systolic blood pressure [SBP] \< 90 mmHg and/or diastolic blood pressure [DBP] \< 50 mmHg)
- Cardiac ejection fraction outside institutional range of normal or \< 50% (whichever is higher) as measured by echocardiogram (or multigated acquisition [MUGA] scan if an echocardiogram can't be performed or is...
- Patients should not have any of the following criteria:
- With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of registration
- Hemoglobin \ = 14 days prior to the determination of a hemoglobin \>= 9 g/dL (\>= 5.59 mmol/L)
- Proteinuria 3+ on dipstick analysis or \> 500 mg/24 hours
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of capivasertib
- History of hypersensitivity to active or inactive excipients of capivasertib or drugs with a similar chemical structure or class to capivasertib
- Current disease or condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
- Previous allogeneic bone marrow transplant
- Known immunodeficiency syndrome
- Concomitant medications (only regarding NF2/CDKN2A/CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1/AKT1/PIK3CA/PTEN genetic alterations):
- Chronic concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors must discontinue the drug for 14 days prior to registration on the study for patients...
- For NF2 patients going on to receive GSK2256098 and for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib: concomitant treatment with strong CYP3A4 inducers or CYP2D6 substrates is not allowed; patients...
- For NF2 patients going on to receive abemaciclib: avoid concomitant use of CYP3A inducers and strong CYP3A inhibitors; use caution with coadministered moderate or weak CYP3A inhibitors
- Diabetic status:
- For patients with NF2 or SMO/PTCH1 mutations: No uncontrolled diabetes defined as a known diabetic with HBA1C \> 7.5 OR fasting glucose \> 140 mg/dL.
- For patients with AKT1/PIK3CA/PTEN mutations:
- Glycosylated hemoglobin (HbA1C) \< 8.0% (63.9 mmol/mol)
- No type 1 diabetes mellitus
- No requirement for insulin for routine diabetic management and control
- No requirement for more than two oral hypoglycemic medications for routine diabetic management and control
- Patients with a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose \< 9.3 mmol/L (167mg/dL); fasting is defined as no caloric intake for at least 8 hours
- Patients without a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose =\< 7.0 mmol/L (126 mg/dL); fasting is defined as no caloric intake for at least 8 hours
- Absolute neutrophil count (ANC) \>= 1,500/mm\^3
- Platelet count \>= 100,000/mm\^3
- Creatinine OR =\ 50 mL/min
- Urine protein:creatinine ratio (UPC) =\< 45 mg/mmol
- Total bilirubin =\< 1.5 x upper limit of normal (ULN); except in case of Gilbert's disease
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
- Sodium, potassium, total calcium (corrected for serum albumin) \& phosphorus within normal limits per institutional guidelines
- QTcF \< 450 msec (QT calculated using Fridericia formula)
- Mean resting heart rate (determined from EKG) 50-100 beats per minute (BMP) (must be obtained from 12-lead EKG defined by a triplicate EKG for patients assigned to the capivasertib arm; patients assigned to all other...
- No uncontrolled medical comorbidities per investigator discretion (e.g. interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small...
- ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Hemoglobin \>= 8 g/dL \ Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; initial...
- ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Prior Treatment
- Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] grade =\< 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral...
- Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy; a washout period of at least 28 days is required between end of radiotherapy and registration
- ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral...
- ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but...
The study team makes the final eligibility decision.
Where it's taking place
- Birmingham, Alabama, United States
- Anchorage, Alaska, United States
- Fairbanks, Alaska, United States
- Kingman, Arizona, United States
- Phoenix, Arizona, United States
- Scottsdale, Arizona, United States
- Fort Smith, Arkansas, United States
- Hot Springs, Arkansas, United States
- Little Rock, Arkansas, United States
- Antioch, California, United States
- Arroyo Grande, California, United States
- Auburn, California, United States
- Berkeley, California, United States
- Burbank, California, United States
- Burlingame, California, United States
- Cameron Park, California, United States
- Carmichael, California, United States
- Castro Valley, California, United States
- Davis, California, United States
- Elk Grove, California, United States
+ 491 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Birmingham, Alabama, United States; Anchorage, Alaska, United States; Fairbanks, Alaska, United States; Kingman, Arizona, United States; Phoenix, Arizona, United States; Scottsdale, Arizona, United States and 505 more location(s). Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.