Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
Intracranial Meningioma, Recurrent Meningioma, NF2 Gene Mutation
About this trial
This is an interventional treatment trial for Intracranial Meningioma
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Anchorage Associates in Radiation MedicineRecruiting
- Anchorage Radiation Therapy CenterRecruiting
- Alaska Breast Care and Surgery LLCRecruiting
- Alaska Oncology and Hematology LLCRecruiting
- Alaska Women's Cancer CareRecruiting
- Anchorage Oncology CentreRecruiting
- Katmai Oncology GroupRecruiting
- Providence Alaska Medical CenterRecruiting
- Kingman Regional Medical CenterRecruiting
- Cancer Center at Saint Joseph'sRecruiting
- Saint Joseph's Hospital and Medical Center
- Mayo Clinic in ArizonaRecruiting
- Arizona Oncology Services Foundation
- Mercy Hospital Fort SmithRecruiting
- CHI Saint Vincent Cancer Center Hot Springs
- Kaiser Permanente-Deer Valley Medical Center
- Mission Hope Medical Oncology - Arroyo GrandeRecruiting
- PCR OncologyRecruiting
- Sutter Auburn Faith Hospital
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick Campus
- Providence Saint Joseph Medical Center/Disney Family Cancer CenterRecruiting
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Mercy Cancer Center �� CarmichaelRecruiting
- Mercy San Juan Medical CenterRecruiting
- Eden Hospital Medical Center
- Sutter Davis Hospital
- Mercy Cancer Center - Elk GroveRecruiting
- Kaiser Permanente-Fremont
- Palo Alto Medical Foundation-Fremont
- Kaiser Permanente-Fresno
- UC San Diego Moores Cancer CenterRecruiting
- Kaiser Permanente Los Angeles Medical CenterRecruiting
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Cedars Sinai Medical CenterRecruiting
- Memorial Medical Center
- Kaiser Permanente-Modesto
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- USC Norris Oncology/Hematology-Newport Beach
- Sutter Cancer Research Consortium
- Kaiser Permanente-Oakland
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- Palo Alto Medical Foundation Health Care
- Keck Medical Center of USC Pasadena
- Kaiser Permanente-Redwood City
- Kaiser Permanente-Richmond
- Mercy Cancer Center - RocklinRecruiting
- Kaiser Permanente-Roseville
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- Mercy Cancer Center - SacramentoRecruiting
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer CenterRecruiting
- Kaiser Permanente-South Sacramento
- Kaiser Permanente - Sacramento
- UC San Diego Medical Center - Hillcrest
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Francisco
- UCSF Medical Center-Parnassus
- UCSF Medical Center-Mission Bay
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Pacific Central Coast Health Center-San Luis ObispoRecruiting
- Mills Health Center
- Kaiser Permanente-San Rafael
- Kaiser San Rafael-Gallinas
- Kaiser Permanente Medical Center - Santa Clara
- Palo Alto Medical Foundation-Santa Cruz
- Mission Hope Medical Oncology - Santa MariaRecruiting
- Kaiser Permanente-Santa Rosa
- Sutter Pacific Medical Foundation
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Palo Alto Medical Foundation-Sunnyvale
- Torrance Memorial Physician Network - Cancer CareRecruiting
- Torrance Memorial Medical CenterRecruiting
- Sutter Cancer Centers Radiation Oncology Services-VacavilleRecruiting
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente-Walnut Creek
- Woodland Memorial HospitalRecruiting
- University of Colorado HospitalRecruiting
- Penrose-Saint Francis HealthcareRecruiting
- Rocky Mountain Cancer Centers-PenroseRecruiting
- Saint Francis Cancer CenterRecruiting
- Porter Adventist HospitalRecruiting
- Mercy Medical CenterRecruiting
- Southwest Oncology PCRecruiting
- Mountain Blue Cancer Care Center
- Grand Valley Oncology
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony HospitalRecruiting
- Littleton Adventist HospitalRecruiting
- Longmont United HospitalRecruiting
- Rocky Mountain Cancer Centers-Longmont
- Parker Adventist HospitalRecruiting
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical CenterRecruiting
- Rocky Mountain Cancer Centers - Pueblo
- Rocky Mountain Cancer Centers-Thornton
- Smilow Cancer Hospital Care Center at Saint FrancisRecruiting
- Yale UniversityRecruiting
- Smilow Cancer Hospital Care Center-TrumbullRecruiting
- Mount Sinai Comprehensive Cancer Center at Aventura
- Boca Raton Regional HospitalRecruiting
- UM Sylvester Comprehensive Cancer Center at Deerfield BeachRecruiting
- Holy Cross HospitalRecruiting
- University of Florida Health Science Center - Gainesville
- Mayo Clinic in FloridaRecruiting
- Mount Sinai Medical Center
- University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
- UM Sylvester Comprehensive Cancer Center at PlantationRecruiting
- Moffitt Cancer Center
- Emory University Hospital Midtown
- Piedmont HospitalRecruiting
- Emory University Hospital/Winship Cancer Institute
- Memorial Health University Medical CenterRecruiting
- Kaiser Permanente Moanalua Medical Center
- Saint Alphonsus Cancer Care Center-BoiseRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Alphonsus Cancer Care Center-CaldwellRecruiting
- Kootenai Health - Coeur d'AleneRecruiting
- Walter Knox Memorial HospitalRecruiting
- Saint Luke's Cancer Institute - FruitlandRecruiting
- Idaho Urologic Institute-MeridianRecruiting
- Saint Luke's Cancer Institute - MeridianRecruiting
- Saint Luke's Cancer Institute - NampaRecruiting
- Saint Alphonsus Cancer Care Center-NampaRecruiting
- Kootenai Clinic Cancer Services - Post FallsRecruiting
- Kootenai Cancer ClinicRecruiting
- Saint Luke's Cancer Institute - Twin FallsRecruiting
- Saint Anthony's HealthRecruiting
- Rush - Copley Medical CenterRecruiting
- Saint Joseph Medical Center
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- Illinois CancerCare-CantonRecruiting
- Memorial Hospital of CarbondaleRecruiting
- SIH Cancer InstituteRecruiting
- Illinois CancerCare-CarthageRecruiting
- Centralia Oncology ClinicRecruiting
- Saint Mary's HospitalRecruiting
- Northwestern UniversityRecruiting
- Rush University Medical CenterRecruiting
- University of IllinoisRecruiting
- Carle at The RiverfrontRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial HospitalRecruiting
- Illinois CancerCare-DixonRecruiting
- Carle Physician Group-EffinghamRecruiting
- Crossroads Cancer CenterRecruiting
- Illinois CancerCare-EurekaRecruiting
- Illinois CancerCare-GalesburgRecruiting
- Western Illinois Cancer Treatment CenterRecruiting
- Northwestern Medicine Cancer Center DelnorRecruiting
- Illinois CancerCare-Kewanee ClinicRecruiting
- Illinois CancerCare-MacombRecruiting
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Good Samaritan Regional Health CenterRecruiting
- Cancer Care Center of O'FallonRecruiting
- Illinois CancerCare-Ottawa ClinicRecruiting
- Radiation Oncology of Northern Illinois
- Illinois CancerCare-PekinRecruiting
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment CenterRecruiting
- Illinois CancerCare-PeoriaRecruiting
- OSF Saint Francis Radiation Oncology at Peoria Cancer CenterRecruiting
- Methodist Medical Center of IllinoisRecruiting
- OSF Saint Francis Medical CenterRecruiting
- Illinois CancerCare-PeruRecruiting
- Valley Radiation OncologyRecruiting
- Illinois CancerCare-PrincetonRecruiting
- Central Illinois Hematology Oncology Center
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Southwest Illinois Health Services LLP
- Carle Cancer CenterRecruiting
- The Carle Foundation HospitalRecruiting
- Northwestern Medicine Cancer Center WarrenvilleRecruiting
- Illinois CancerCare - WashingtonRecruiting
- Rush-Copley Healthcare CenterRecruiting
- Memorial Regional Cancer Center Day Road
- Reid Health
- Memorial Hospital of South Bend
- Mary Greeley Medical CenterRecruiting
- McFarland Clinic - AmesRecruiting
- McFarland Clinic - BooneRecruiting
- Medical Oncology and Hematology Associates-West Des MoinesRecruiting
- Mercy Cancer Center-West LakesRecruiting
- Alegent Health Mercy HospitalRecruiting
- Greater Regional Medical CenterRecruiting
- Mercy Medical Center - Des MoinesRecruiting
- Mission Cancer and Blood - LaurelRecruiting
- McFarland Clinic - Trinity Cancer CenterRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- McFarland Clinic - JeffersonRecruiting
- McFarland Clinic - MarshalltownRecruiting
- Mercy Medical Center-West LakesRecruiting
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Central Care Cancer Center - Great BendRecruiting
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Kansas Institute of Medicine Cancer and Blood Center
- Minimally Invasive Surgery Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas-Manhattan
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Menorah Medical Center
- Saint Luke's South Hospital
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Cancer Center of Kansas - Winfield
- Flaget Memorial HospitalRecruiting
- Commonwealth Cancer Center-CorbinRecruiting
- Oncology Hematology Care Inc-Crestview
- Saint Joseph HospitalRecruiting
- Saint Joseph Radiation Oncology Resource CenterRecruiting
- Saint Joseph Hospital EastRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Saint Joseph LondonRecruiting
- Jewish Hospital
- Saints Mary and Elizabeth Hospital
- Norton Brownsboro Hospital and Medical CampusRecruiting
- UofL Health Medical Center Northeast
- Saint Joseph Mount SterlingRecruiting
- Jewish Hospital Medical Center South
- West Jefferson Medical Center
- Louisiana State University Health Science Center
- University Medical Center New Orleans
- University of Maryland/Greenebaum Cancer CenterRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Tufts Medical CenterRecruiting
- Massachusetts General Hospital Cancer CenterRecruiting
- Dana-Farber Cancer Institute
- UMass Memorial Medical Center - University CampusRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Bronson Battle CreekRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Henry Ford Cancer Institute-Downriver
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Caro Cancer CenterRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Hematology Oncology Consultants-ClarkstonRecruiting
- Newland Medical Associates-ClarkstonRecruiting
- Henry Ford Macomb Hospital-Clinton Township
- Beaumont Hospital - Dearborn
- Henry Ford Medical Center-Fairlane
- Henry Ford Hospital
- Ascension Saint John HospitalRecruiting
- Great Lakes Cancer Management Specialists-Doctors ParkRecruiting
- Genesee Cancer and Blood Disease Treatment CenterRecruiting
- Genesee Hematology Oncology PCRecruiting
- Genesys Hurley Cancer InstituteRecruiting
- Hurley Medical CenterRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Spectrum Health at Butterworth CampusRecruiting
- Trinity Health Grand Rapids HospitalRecruiting
- Academic Hematology Oncology SpecialistsRecruiting
- Great Lakes Cancer Management Specialists-Van Elslander Cancer CenterRecruiting
- Michigan Breast Specialists-Grosse Pointe Woods
- Allegiance Health
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer CenterRecruiting
- Ascension Borgess Cancer CenterRecruiting
- Borgess Medical CenterRecruiting
- Sparrow HospitalRecruiting
- Hope Cancer Clinic
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- Great Lakes Cancer Management Specialists-Macomb Medical CampusRecruiting
- Michigan Breast Specialists-Macomb Township
- Saint Mary's Oncology/Hematology Associates of MarletteRecruiting
- Trinity Health Muskegon HospitalRecruiting
- Lakeland Hospital NilesRecruiting
- Cancer and Hematology Centers of Western Michigan - Norton ShoresRecruiting
- Henry Ford Medical Center-Columbus
- 21st Century Oncology-PontiacRecruiting
- Hope Cancer CenterRecruiting
- Newland Medical Associates-PontiacRecruiting
- Saint Joseph Mercy OaklandRecruiting
- Lake Huron Medical Center
- Spectrum Health Reed City HospitalRecruiting
- Great Lakes Cancer Management Specialists-Rochester Hills
- Ascension Saint Mary's HospitalRecruiting
- Oncology Hematology Associates of Saginaw Valley PCRecruiting
- Lakeland Medical Center Saint JosephRecruiting
- Marie Yeager Cancer CenterRecruiting
- Henry Ford Macomb Health Center - Shelby Township
- Bhadresh Nayak MD PC-Sterling HeightsRecruiting
- Ascension Saint Joseph HospitalRecruiting
- Munson Medical CenterRecruiting
- Advanced Breast Care Center PLLCRecruiting
- Great Lakes Cancer Management Specialists-Macomb Professional BuildingRecruiting
- Macomb Hematology Oncology PCRecruiting
- Michigan Breast Specialists-WarrenRecruiting
- Saint John Macomb-Oakland HospitalRecruiting
- Henry Ford West Bloomfield Hospital
- Saint Mary's Oncology/Hematology Associates of West BranchRecruiting
- University of Michigan Health - WestRecruiting
- Huron Gastroenterology PCRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Riverwood Healthcare CenterRecruiting
- Essentia Health - Baxter ClinicRecruiting
- Essentia Health Saint Joseph's Medical CenterRecruiting
- Fairview Ridges Hospital
- Minnesota Oncology - BurnsvilleRecruiting
- Cambridge Medical CenterRecruiting
- Mercy HospitalRecruiting
- Essentia Health - Deer River ClinicRecruiting
- Essentia Health Saint Mary's - Detroit Lakes ClinicRecruiting
- Essentia Health Cancer CenterRecruiting
- Essentia Health Saint Mary's Medical CenterRecruiting
- Miller-Dwan HospitalRecruiting
- Fairview Southdale HospitalRecruiting
- Essentia Health - Ely ClinicRecruiting
- Lake Region Healthcare Corporation-Cancer Care
- Essentia Health - FosstonRecruiting
- Unity HospitalRecruiting
- Essentia Health Hibbing ClinicRecruiting
- Essentia Health - International Falls ClinicRecruiting
- Fairview Clinics and Surgery Center Maple GroveRecruiting
- Minnesota Oncology Hematology PA-MaplewoodRecruiting
- Saint John's Hospital - HealtheastRecruiting
- Abbott-Northwestern HospitalRecruiting
- Hennepin County Medical CenterRecruiting
- Health Partners IncRecruiting
- Monticello Cancer CenterRecruiting
- Essentia Health - Moose Lake ClinicRecruiting
- New Ulm Medical CenterRecruiting
- Essentia Health - Park RapidsRecruiting
- Fairview Northland Medical CenterRecruiting
- North Memorial Medical Health CenterRecruiting
- Mayo Clinic in RochesterRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- Regions HospitalRecruiting
- United HospitalRecruiting
- Essentia Health SandstoneRecruiting
- Saint Francis Regional Medical CenterRecruiting
- Lakeview HospitalRecruiting
- Essentia Health Virginia ClinicRecruiting
- Ridgeview Medical CenterRecruiting
- Rice Memorial HospitalRecruiting
- Minnesota Oncology Hematology PA-WoodburyRecruiting
- Fairview Lakes Medical CenterRecruiting
- University of Mississippi Medical CenterRecruiting
- Saint Louis Cancer and Breast Institute-BallwinRecruiting
- Central Care Cancer Center - Bolivar
- Parkland Health Center-Bonne Terre
- Cox Cancer Center BransonRecruiting
- Saint Francis Medical CenterRecruiting
- Southeast Cancer CenterRecruiting
- Parkland Health Center - FarmingtonRecruiting
- Centerpoint Medical Center LLC
- Capital Region Southwest CampusRecruiting
- Freeman Health SystemRecruiting
- Mercy Hospital JoplinRecruiting
- Saint Luke's Hospital of Kansas City
- Research Medical Center
- Saint Luke's East - Lee's Summit
- Liberty Radiation Oncology Center
- Delbert Day Cancer Institute at PCRMCRecruiting
- Mercy Clinic-Rolla-Cancer and HematologyRecruiting
- Heartland Regional Medical CenterRecruiting
- Saint Louis Cancer and Breast Institute-South CityRecruiting
- Barnes-Jewish Hospital
- Washington University School of MedicineRecruiting
- Mercy Hospital SouthRecruiting
- Missouri Baptist Medical CenterRecruiting
- Mercy Hospital Saint LouisRecruiting
- Sainte Genevieve County Memorial HospitalRecruiting
- Mercy Hospital SpringfieldRecruiting
- CoxHealth South HospitalRecruiting
- Missouri Baptist Sullivan HospitalRecruiting
- Missouri Baptist Outpatient Center-Sunset HillsRecruiting
- Mercy Hospital WashingtonRecruiting
- Billings Clinic Cancer CenterRecruiting
- Saint Vincent Healthcare
- Bozeman Deaconess HospitalRecruiting
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer InstituteRecruiting
- Saint Peter's Community Hospital
- Kalispell Regional Medical CenterRecruiting
- Saint Patrick Hospital - Community HospitalRecruiting
- Community Medical HospitalRecruiting
- Nebraska Medicine-BellevueRecruiting
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good SamaritanRecruiting
- Saint Elizabeth Regional Medical CenterRecruiting
- Nebraska Medicine-Village PointeRecruiting
- Alegent Health Immanuel Medical CenterRecruiting
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical CenterRecruiting
- Alegent Health Lakeside HospitalRecruiting
- Creighton University Medical CenterRecruiting
- University of Nebraska Medical CenterRecruiting
- Midlands Community HospitalRecruiting
- Carson Tahoe Regional Medical CenterRecruiting
- Cancer and Blood Specialists-HendersonRecruiting
- Comprehensive Cancer Centers of Nevada - HendersonRecruiting
- Comprehensive Cancer Centers of Nevada-Horizon RidgeRecruiting
- Las Vegas Cancer Center-Henderson
- OptumCare Cancer Care at Seven HillsRecruiting
- Comprehensive Cancer Centers of Nevada-Southeast HendersonRecruiting
- GenesisCare USA - HendersonRecruiting
- Las Vegas Urology - Green ValleyRecruiting
- Las Vegas Urology - PebbleRecruiting
- Urology Specialists of Nevada - Green ValleyRecruiting
- Las Vegas Urology - PecosRecruiting
- Desert West Surgery
- OptumCare Cancer Care at CharlestonRecruiting
- University Medical Center of Southern NevadaRecruiting
- Hope Cancer Care of NevadaRecruiting
- Cancer and Blood Specialists-Shadow
- Radiation Oncology Centers of Nevada CentralRecruiting
- Urology Specialists of Nevada - CentralRecruiting
- GenesisCare USA - Las VegasRecruiting
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
- Sunrise Hospital and Medical CenterRecruiting
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
- Las Vegas Prostate Cancer CenterRecruiting
- Las Vegas Urology - SunsetRecruiting
- Urology Specialists of Nevada - SouthwestRecruiting
- Radiation Oncology Centers of Nevada SoutheastRecruiting
- Cancer Therapy and Integrative Medicine
- Ann M Wierman MD LTDRecruiting
- Cancer and Blood Specialists-Tenaya
- Comprehensive Cancer Centers of Nevada - NorthwestRecruiting
- GenesisCare USA - Vegas TenayaRecruiting
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
- Las Vegas Urology - Cathedral RockRecruiting
- Las Vegas Urology - Smoke RanchRecruiting
- OptumCare Cancer Care at MountainViewRecruiting
- Urology Specialists of Nevada - NorthwestRecruiting
- Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
- Comprehensive Cancer Centers of Nevada - Town CenterRecruiting
- Comprehensive Cancer Centers of Nevada-SummerlinRecruiting
- Summerlin Hospital Medical CenterRecruiting
- Las Vegas Cancer Center-Medical Center
- Comprehensive Cancer Centers of NevadaRecruiting
- GenesisCare USA - Fort ApacheRecruiting
- OptumCare Cancer Care at Fort ApacheRecruiting
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
- Comprehensive Cancer Centers of Nevada - Central ValleyRecruiting
- University Cancer CenterRecruiting
- Hope Cancer Care of Nevada-PahrumpRecruiting
- Renown Regional Medical CenterRecruiting
- Saint Mary's Regional Medical CenterRecruiting
- Radiation Oncology AssociatesRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Memorial Sloan Kettering Basking RidgeRecruiting
- Hackensack University Medical Center
- Overlook HospitalRecruiting
- University of New Mexico Cancer CenterRecruiting
- Montefiore Medical Center-Einstein Campus
- Montefiore Medical Center-Weiler Hospital
- Montefiore Medical Center - Moses Campus
- Memorial Sloan Kettering CommackRecruiting
- Glens Falls HospitalRecruiting
- Memorial Sloan Kettering WestchesterRecruiting
- Northwell Health/Center for Advanced MedicineRecruiting
- North Shore University Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Lenox Hill Hospital
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- NYP/Weill Cornell Medical CenterRecruiting
- University of Rochester
- AdventHealth Infusion Center Asheville
- UNC Lineberger Comprehensive Cancer Center
- East Carolina University
- AdventHealth Hendersonville
- Wake Forest University Health SciencesRecruiting
- Essentia Health Cancer Center-South University ClinicRecruiting
- Essentia Health - Jamestown ClinicRecruiting
- Indu and Raj Soin Medical Center
- Strecker Cancer Center-BelpreRecruiting
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Adena Regional Medical CenterRecruiting
- Oncology Hematology Care Inc-Eden Park
- Oncology Hematology Care Inc-Mercy West
- University of Cincinnati Cancer Center-UC Medical CenterRecruiting
- Good Samaritan Hospital - CincinnatiRecruiting
- Oncology Hematology Care Inc-Anderson
- Oncology Hematology Care Inc-Kenwood
- Bethesda North HospitalRecruiting
- Oncology Hematology Care Inc-Blue Ash
- TriHealth Cancer Institute-WestsideRecruiting
- TriHealth Cancer Institute-AndersonRecruiting
- Cleveland Clinic FoundationRecruiting
- Ohio State University Comprehensive Cancer CenterRecruiting
- Mount Carmel East HospitalRecruiting
- Columbus Oncology and Hematology Associates IncRecruiting
- Riverside Methodist HospitalRecruiting
- Grant Medical CenterRecruiting
- The Mark H Zangmeister CenterRecruiting
- Mount Carmel Health Center WestRecruiting
- Doctors HospitalRecruiting
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Delaware Health Center-Grady Cancer CenterRecruiting
- Delaware Radiation Oncology
- Grady Memorial HospitalRecruiting
- Columbus Oncology and Hematology AssociatesRecruiting
- Oncology Hematology Care Inc-Healthplex
- Armes Family Cancer Center
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-Atrium
- Dayton Physicians LLC-Wayne
- Wayne Hospital
- Mount Carmel Grove City HospitalRecruiting
- Zangmeister Center Grove CityRecruiting
- Greater Dayton Cancer Center
- First Dayton Cancer Care
- Kettering Medical Center
- Fairfield Medical CenterRecruiting
- Saint Rita's Medical CenterRecruiting
- OhioHealth Mansfield HospitalRecruiting
- Marietta Memorial HospitalRecruiting
- OhioHealth Marion General HospitalRecruiting
- Dayton Physicians LLC-Signal Point
- Knox Community HospitalRecruiting
- Mount Carmel New Albany Surgical HospitalRecruiting
- Licking Memorial HospitalRecruiting
- Newark Radiation OncologyRecruiting
- Mercy Health Perrysburg Cancer CenterRecruiting
- Southern Ohio Medical CenterRecruiting
- Dayton Physicians LLC-Wilson
- Springfield Regional Cancer CenterRecruiting
- Springfield Regional Medical CenterRecruiting
- Saint Vincent Mercy Medical CenterRecruiting
- Mercy Health - Saint Anne HospitalRecruiting
- Dayton Physicians LLC - Troy
- Upper Valley Medical Center
- University of Cincinnati Cancer Center-West ChesterRecruiting
- Saint Ann's HospitalRecruiting
- Genesis Healthcare System Cancer Care CenterRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Mercy Hospital Oklahoma CityRecruiting
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Saint Alphonsus Medical Center-Baker CityRecruiting
- Saint Charles Health SystemRecruiting
- Clackamas Radiation Oncology CenterRecruiting
- Providence Cancer Institute Clackamas ClinicRecruiting
- Bay Area HospitalRecruiting
- Providence Newberg Medical CenterRecruiting
- Saint Alphonsus Medical Center-OntarioRecruiting
- Providence Willamette Falls Medical CenterRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Saint Charles Health System-RedmondRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- UPMC-Heritage Valley Health System Beaver
- Lehigh Valley Hospital - MuhlenbergRecruiting
- Geisinger Medical Center
- Pocono Medical CenterRecruiting
- UPMC Cancer Centers - Arnold Palmer Pavilion
- Geisinger Medical Center-Cancer Center Hazleton
- Lehigh Valley Hospital-HazletonRecruiting
- Penn State Milton S Hershey Medical CenterRecruiting
- UPMC-Johnstown/John P. Murtha Regional Cancer Center
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- UPMC Cancer Center at UPMC McKeesport
- UPMC Hillman Cancer Center in Coraopolis
- UPMC-Magee Womens Hospital
- UPMC-Presbyterian Hospital
- UPMC-Saint Margaret
- University of Pittsburgh Cancer Institute (UPCI)Recruiting
- UPMC-Shadyside Hospital
- UPMC Jefferson Regional Radiation Oncology
- UPMC-Passavant Hospital
- UPMC-Saint Clair Hospital Cancer Center
- Geisinger Cancer Services-Pottsville
- Community Medical Center
- Geisinger Medical Oncology-Selinsgrove
- UPMC Cancer Center at UPMC Northwest
- Geisinger Medical Group
- UPMC Uniontown Hospital Radiation Oncology
- UPMC Washington Hospital Radiation Oncology
- Geisinger Wyoming Valley/Henry Cancer Center
- Rhode Island Hospital
- Prisma Health Cancer Institute - SpartanburgRecruiting
- Medical University of South Carolina
- Prisma Health Cancer Institute - EasleyRecruiting
- Gibbs Cancer Center-Gaffney
- Greenville Health System Cancer Institute-Andrews
- Prisma Health Cancer Institute - ButternutRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Greenville Memorial HospitalRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Gibbs Cancer Center-Pelham
- Prisma Health Cancer Institute - SenecaRecruiting
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Memorial Hospital
- Vanderbilt-Ingram Cancer Center Cool Springs
- Pulmonary Medicine Center of Chattanooga-Hixson
- Vanderbilt Breast Center at One Hundred Oaks
- Vanderbilt University/Ingram Cancer Center
- Memorial GYN Plus
- Dell Seton Medical Center at The University of Texas
- Saint Joseph Regional Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- M D Anderson Cancer CenterRecruiting
- Memorial Hermann Texas Medical CenterRecruiting
- Memorial Hermann Northeast HospitalRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Memorial Hermann The Woodlands HospitalRecruiting
- Farmington Health Center
- Huntsman Cancer Institute/University of UtahRecruiting
- South Jordan Health Center
- Central Vermont Medical Center/National Life Cancer TreatmentRecruiting
- University of Vermont Medical CenterRecruiting
- University of Vermont and State Agricultural CollegeRecruiting
- Norris Cotton Cancer Center-NorthRecruiting
- University of Virginia Cancer CenterRecruiting
- Inova Schar Cancer InstituteRecruiting
- Inova Fairfax Hospital
- Providence Regional Cancer System-AberdeenRecruiting
- Cancer Care Center at Island Hospital
- Overlake Medical Center
- PeaceHealth Saint Joseph Medical CenterRecruiting
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical CenterRecruiting
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-CentraliaRecruiting
- Swedish Cancer Institute-EdmondsRecruiting
- Saint Elizabeth Hospital
- Providence Regional Cancer PartnershipRecruiting
- Saint Francis Hospital
- Swedish Cancer Institute-IssaquahRecruiting
- Kadlec Clinic Hematology and OncologyRecruiting
- Providence Regional Cancer System-LaceyRecruiting
- Saint Clare Hospital
- PeaceHealth Saint John Medical CenterRecruiting
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Peninsula Cancer Center
- Valley Medical CenterRecruiting
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard CampusRecruiting
- Kaiser Permanente Washington
- Swedish Medical Center-Cherry HillRecruiting
- Swedish Medical Center-First HillRecruiting
- PeaceHealth United General Medical CenterRecruiting
- Olympic Medical Cancer Care Center
- Providence Regional Cancer System-SheltonRecruiting
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
- MultiCare Deaconess Cancer and Blood Specialty Center - North
- Franciscan Research Center-Northwest Medical Plaza
- Northwest Medical Specialties PLLC
- PeaceHealth Southwest Medical CenterRecruiting
- Providence Saint Mary Regional Cancer CenterRecruiting
- North Star Lodge Cancer Center at Yakima Valley Memorial HospitalRecruiting
- Providence Regional Cancer System-YelmRecruiting
- United Hospital Center
- WVUH-Berkely Medical Center
- West Virginia University Healthcare
- Camden Clark Medical Center
- Duluth Clinic AshlandRecruiting
- Northwest Wisconsin Cancer CenterRecruiting
- Aurora Cancer Care-Southern Lakes VLCCRecruiting
- Marshfield Clinic-Chippewa CenterRecruiting
- Aurora Saint Luke's South ShoreRecruiting
- Marshfield Clinic Cancer Center at Sacred Heart
- Marshfield Medical Center-EC Cancer CenterRecruiting
- Aurora Health Center-Fond du LacRecruiting
- Aurora Health Care Germantown Health CenterRecruiting
- Aurora Cancer Care-GraftonRecruiting
- Aurora BayCare Medical CenterRecruiting
- Aurora Cancer Care-Kenosha SouthRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- University of Wisconsin Carbone Cancer Center
- Aurora Bay Area Medical Group-MarinetteRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Aurora Cancer Care-MilwaukeeRecruiting
- Aurora Saint Luke's Medical CenterRecruiting
- Medical College of Wisconsin
- Aurora Sinai Medical CenterRecruiting
- Marshfield Clinic-Minocqua CenterRecruiting
- ProHealth D N Greenwald Center
- Cancer Center of Western WisconsinRecruiting
- ProHealth Oconomowoc Memorial Hospital
- Vince Lombardi Cancer Clinic - OshkoshRecruiting
- Aurora Cancer Care-RacineRecruiting
- Marshfield Medical Center-Rice LakeRecruiting
- Vince Lombardi Cancer Clinic-SheboyganRecruiting
- Ascension Saint Michael's Hospital
- Marshfield Medical Center-River Region at Stevens PointRecruiting
- Aurora Medical Center in SummitRecruiting
- Vince Lombardi Cancer Clinic-Two RiversRecruiting
- Aurora Cancer Care-Waukesha
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
- Marshfield Clinic-Wausau CenterRecruiting
- Aurora Cancer Care-Milwaukee WestRecruiting
- Aurora West Allis Medical CenterRecruiting
- Marshfield Medical Center - WestonRecruiting
- Big Horn Basin Cancer Center
- Billings Clinic-CodyRecruiting
- Welch Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Arm A (vismodegib)
Arm B (FAK inhibitor GSK2256098)
Arm C (capivasertib)
Arm D (abemaciclib)
Patients receive vismodegib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL FEBRUARY 2018)
Patients receive FAK inhibitor GSK2256098 PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL JULY 2017)
Patients receive capivasertib PO BID on days 1-4. Treatment repeats every 7 days for up to 1 cycle (28 days) in the absence of disease progression or unacceptable toxicity.
Patients receive abemaciclib PO Q12H. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.