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NCT02523014 · Alliance for Clinical Trials in Oncology

Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas

What this study is about

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.

View original scientific description

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.

Interventions

DRUG

Vismodegib

Given PO

DRUG

FAK Inhibitor GSK2256098

Given PO

DRUG

Capivasertib

Given PO

DRUG

Abemaciclib

Given PO

Primary outcome measures

Progression free survival (PFS)

Time frame: At 6 months

Point estimates and 95% binomial confidence intervals will be generated for the six month PFS rate within each cohort of each treatment arm. Kaplan-Meier curves will be generated for PFS for each cohort within each treatment arm.

Response rate defined as a confirmed complete response (CR) or partial response (PR)

Time frame: Up to 2 years

Point estimates will be generated for response rates within each treatment arm with corresponding 95% binomial confidence intervals.

Who can participate

This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.

Inclusion criteria

  • 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 by the central laboratory, regardless of whether prior genotype testing outside of the central laboratory was performed
  • 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 of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 25 months; for patients with SMO/PTCH1 mutations enrolling to receive vismodegib, the change can occur between scans separated by up to 25 months; residual measurable disease will be defined by bidimensionally measurable lesions with clearly defined margins by MRI scans, with a minimum diameter of 10 mm in both dimensions
  • 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 25 months
  • 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 progressive meningioma lesion has been radiated, at least 24 weeks must have elapsed from completion of radiation to registration; if the progressive lesion is outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
  • 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 both dimensions; multifocal disease is allowed
  • 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 outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
  • 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 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • 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 long QT syndrome, or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
  • 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 Heart Association (NYHA) class \>= II
  • 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 inconclusive); left ventricular ejection fraction (LVEF) below lower limit of normal for site
  • 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 \< 9 g/dL (\< 5.59 mmol/L); note: any blood transfusion must be \>= 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 with NF2 mutation enrolled to GSK2256098, as well as for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib
  • 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 must discontinue the drug 14 days prior to registration
  • 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 =\< 1.5 mg/dl x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \> 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 arms will require a single EKG
  • 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 bowel, or pre-existing Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
  • 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 treatment must not begin earlier than the day after the erythrocyte transfusion
  • 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 neuropathy prior to registration; a washout period of at least 28 days is required between last chemotherapy dose and registration (provided the patient did not receive radiotherapy)
  • 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 infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]); screening is not required for enrollment in the absence of symptoms
  • 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 not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest

Where

  • Birmingham, Alabama
  • Anchorage, Alaska
  • Fairbanks, Alaska
  • Kingman, Arizona
  • Phoenix, Arizona
  • Scottsdale, Arizona
  • Fort Smith, Arkansas
  • Hot Springs, Arkansas
  • Little Rock, Arkansas
  • Antioch, California
  • Arroyo Grande, California
  • Auburn, California

And 502 more locations — see the full list below.

Collaborators

National Cancer Institute (NCI), GlaxoSmithKline, Genentech, Inc., Brain Science Foundation

Related conditions & keywords

Intracranial MeningiomaRecurrent MeningiomaNF2 Gene Mutation

Frequently asked questions

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.

Data: ClinicalTrials.gov · synced Oct 2, 2026 · Source of record for eligibility and locations

📊
1 of 124 participants interested
1% interest

See if this study fits

A short prescreen based on this study's listed criteria. A coordinator confirms eligibility — this is not a medical assessment.

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Study locations

Choose your preferred location, or select flexible during enrollment.

ACTIVE_NOT_RECRUITING

Birmingham

Alabama

Location available
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Anchorage

Alaska

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Anchorage

Alaska

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Anchorage

Alaska

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SUSPENDED

Anchorage

Alaska

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SUSPENDED

Anchorage

Alaska

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Anchorage

Alaska

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Anchorage

Alaska

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Anchorage

Alaska

Location available

And 775 more locations available.

Express your interest

Share your contact details and a study coordinator can follow up about screening.

Secure & Confidential

Your information is protected and will only be shared with the research team.

What participation can include

  • Study-related care provided by the research team
  • Close monitoring by medical professionals
  • Possible compensation for time and travel*
  • The option to withdraw at any time
  • Contributing to medical research that may help future patients

*Compensation varies by study. Confirm details with coordinator.

Typical next steps

  1. 1.Submit this form
  2. 2.Phone screening
  3. 3.In-person assessment if eligible
  4. 4.Begin participation

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Looking for Meningiomas Treatment in Birmingham?

Join others in Alabama exploring innovative treatment options through clinical research

Meningiomas Treatment Options in Birmingham, Alabama

If you're searching for Meningiomas treatment in Birmingham, participating in a clinical research study may provide access to innovative approaches under expert medical supervision. This study is actively recruiting participants in Birmingham, Anchorage, Fairbanks and surrounding areas.

Clinical trials offer participants the opportunity to receive cutting-edge treatments while contributing to medical research that may help future patients with Meningiomas. All study-related care is provided at no cost to participants.

Local Sites
3 locations in Alabama
Now Enrolling
Up to 124 participants
Quick Start
Screening available now

Why Consider a Clinical Trial for Meningiomas?

Potential Benefits

  • ✓Access to new treatment approaches before public availability
  • ✓Close monitoring by experienced medical professionals
  • ✓Study-related care provided at no cost
  • ✓Contribute to medical research for Meningiomas

What to Expect

  • →Initial screening to determine eligibility
  • →Regular check-ups and monitoring visits
  • →Possible compensation for time and travel
  • →You can withdraw at any time

Frequently Asked Questions About This Meningiomas Study

Important Clinical Trial Information

This information is provided for educational purposes and does not constitute medical advice. Clinical trial participation involves potential risks and benefits. Eligibility requirements apply and will be assessed during the screening process.

Study identifier: NCT02523014. For complete study details, visit ClinicalTrials.gov. Always consult with your healthcare provider before making decisions about your medical care or participating in clinical research.