Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
|Eligible Ages||18 Months and Over|
- - All participants must meet the following criteria on screening examination to be eligible to participate in the study: - Participants must be able to understand and willing to sign a written informed consent document.
- - Participants must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
- - Participants must be at least 18 years old on day of signing informed consent.
- - Participants must have a Karnofsky Performance Status (KPS) ≥ 70 (see Appendix A).
- - Participants must be able to swallow oral medications.
- - Nature of illness and treatment history - Participants must have histologically confirmed diagnosis of glioblastoma or variants.
- - To be eligible for the study all participants (Cohort 1 and 2) are required to provide genomic profiling data from a sequencing-based assay and must include reporting of the RB1 gene in explicit terms within the report.
- - Inactivation of CDKN2A/B or C in the tumor by homozygous deletion (evidence for more than single copy loss for any of the genes defined as copy array log2 ratio of <0.3 by copy array; or from sequencing data with sufficient coverage for evaluation).
- - Validation of wild-type RB status (no deletion/losses more than single copy by copy number or sequencing data; and/or no inactivating mutations or rearrangement by sequencing).
- - Participants must be at first relapse of GBM.
- - Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
- - For Cohort 2 subjects, CT or MRI within 14 days prior to study registration.
- - For Cohort 1 subjects, CT or MRI should be performed ideally within 14 days prior to study registration, but because the screening MRI for this subset of subjects will not be used for evaluation of response, it is acceptable for this MRI/CT to have been performed greater than 14 days prior to registration if unavoidable.
- - Confirmation of availability of sufficient tissue from a prior surgery demonstrating glioblastoma or variants for correlative studies is required prior to enrollment; these samples must be sent to the DFCI Coordinating Center within 60 days of registration.
- - 20 unstained formalin fixed paraffin embedded (FFPE) sections (standard 5 micrometer thickness) - For Cohort 1 subjects, there must be > 2cm2 enhancing tissue available for resection and submission for study correlatives as determined by local treating team.
- - Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).
- - From the projected start of scheduled study treatment, the following time periods must have elapsed: - 4 weeks or 5 half-lives (whichever is shorter) from any investigational agent; - 4 weeks from cytotoxic therapy (except 23 days for temozolomide; 6 weeks from nitrosoureas); - 4 weeks from antibodies; - 4 weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies.
- - 2 days from Novo-TTF - Participants with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of progressive disease based upon nuclear imaging, MR spectroscopy, perfusion imaging or histopathology.
- - Participants having undergone recent resection or open biopsy or stereotactic biopsy of recurrent or progressive tumor will be eligible for Cohort 2 as long as the following conditions apply: - They have recovered from the effects of surgery.
- - Residual disease following resection of recurrent tumor is not mandated for eligibility.
- - Clinical labs - performed within 14 days prior to registration - Hematology: - Leukocytes ≥ 3 K/µL - Absolute neutrophil count (ANC) ≥ 1.5 K/µL - Platelet count ≥ 100 K/µL - Absolute Lymphocyte Count ≥ 0.5 K/µL - Hemoglobin ≥ 8.0 g/dL - Biochemistry: - Total serum calcium (corrected for serum albumin as needed) or ionized calcium within institution's normal range, or correctable with supplements.
- - Magnesium within institution's normal range, or correctable with supplements.
- - AST (SGOT) and ALT (SGPT) ≤ 2.5 x institution's ULN (or ≤ 5 X institutional ULN for subjects with Gilberts syndrome) - Serum bilirubin ≤ 1.5 x institution's ULN - Serum creatinine ≤ 1.5 x institution's ULN or calculated 24-hour creatinine clearance ≥ 50 mL/min - Serum amylase ≤ 1.5 x institution's ULN - Serum lipase ≤ 1.5 x institution's ULN - Serum albumin ≥ 2.5 g/dL - Coagulation studies: - INR < 2.0 - PTT ≤ institution's ULN, unless receiving therapeutic low molecular weight heparin or oral factor Xa inhibitors.
- - Other illnesses -- Patients with prior or concurrent malignancy whose natural history or treatment does not give the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- - Pregnancy and Reproduction - The effects of abemaciclib and pembrolizumab on the developing human fetus are unknown.
- - Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to first dose of abemaciclib.
- - Participants who meet any of the following criteria will not be eligible for admission into the study.
- - Pathology - Prior evidence of 1p/19q co-deletion.
- - IDH1/2 mutation in any prior biopsy.
- - Tumor primarily localized to the brainstem or spinal cord.
- - Presence of diffuse leptomeningeal disease or extracranial disease.
- - Previous therapies - Participants who have received prior treatment with a CDK4/6 inhibitor (e.g. abemaciclib, palbociclib).
- - Participants who have received anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL184, sunitinib etc.).
- - Participants who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- - Participants who have received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection (including intra-tumoral vaccines) or convection enhanced delivery.
- - Concomitant medications - Participants requiring treatment with high dose systemic corticosteroids defined as dexamethasone > 2 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of start of study drug.
- - Participants who have received systemic immunosuppressive treatments, aside from systemic corticosteroids (such as methotrexate, chloroquine, azathioprine, etc.) within six months of start of study drug.
- - Participants taking an enzyme-inducing anti-epileptic drug (EIAED): phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, oxcarbazepine, eslicarbazepine, rufinamide, and felbamate.
- - Participants taking a drug known to be a strong inhibitor or inducer of isoenzyme CYP3A (Appendix D).
- - Participants receiving any other investigational agents.
- - Current use of herbal preparations/medications, including but not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng.
- - Current use of warfarin sodium or any other coumadin-derivative anticoagulant.
- - Other illnesses - History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib and/or pembrolizumab.
- - History of intratumoral or peritumoral hemorrhage if deemed significant by the treating investigator.
- - Uncontrolled intercurrent illness.
- - Participant has an active infection requiring systemic therapy and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen or hepatitis C antibodies).
- - Participant with a known history of active TB (Bacillus Tuberculosis).
- - Participant with active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- - Participant with a diagnosis of immunodeficiency, including a known history of Human Immunodeficiency Virus (HIV).
- - Participants who have received a live vaccine within 30 days prior to start of study treatment.
- - Participant has active cardiac disease including any of the following: - Angina pectoris that requires the use of anti-anginal medications.
- - Ventricular arrhythmias except for benign premature ventricular contractions.
- - Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication.
- - Conduction abnormality requiring a pacemaker.
- - Valvular disease with document compromise in cardiac function.
- - Symptomatic pericarditis.
- - Participant has a history of cardiac dysfunction including any of the following: - Myocardial infarction within the last 6 months prior to start of study drug, documents by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function.
- - History of documents congestive heart failure (New York Heart Association functional classification III-IV, see Appendix I).
- - Documented cardiomyopathy.
- - Congenital long QT syndrome.
- - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of abemaciclib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or extensive small bowel resection).
- - Participants who have undergone major systemic surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
- - Participants who are pregnant or breastfeeding.
- - Participants with history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug or gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of start of study drug.
- - Has known history of, or any evidence of, active non-infectious pneumonitis.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|Dana-Farber Cancer Institute|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Patrick Wen, MD|
|Principal Investigator Affiliation||Dana-Farber Cancer Institute|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Overall Status||Not yet recruiting|
The disease, disorder, syndrome, illness, or injury that is being studied.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. Many brain cancers show over expression of a protein called cyclin D1. That means that the body makes too much cyclin D1, which affects enzymes called CDK 4 and CDK 6. Enzymes are substances in the body that help reactions between cells happen. Too much cyclin D1 triggers CDK 4 and CDK 6 to make more cells than normal. This extra cell production leads to the growth of tumors. In laboratory studies, abemaciclib was able to enter the brain, stop CDK 4 and CDK 6 from making cells, and slow growth of glioblastoma in mice. Pembrolizumab (MK-3475) has been studied in lab experiments and in other types of cancer. Information from these studies suggests that Pembrolizumab (MK-3475) may be beneficial inrecurrent glioblastoma (GBM). Pembrolizumab (MK-3475) is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients; an antibody that is made in the lab is also known as a humanized monoclonal antibody that is designed to block the action of the receptor, PD-1. PD-1 works to help tumor cells continue to grow and multiply. There are now several approved antibodies for the therapy of cancer and other diseases. .
Experimental: Surgery Arm
In the surgical arm participants who require reoperation and have evidence of CDKN2A/B or C loss and intact RB from a prior tumor sample will receive Pembrolizumab-prior to surgery, at predetermined dose and time point Abemaciclib: every 12 hours from the day of pembrolizumab infusion to the morning of surgery Post surgery Participants with receive Abemaciclib, twice daily oral at specified dose for 21 day cycle Pembrolizumab intravenous once in 21 day cycle (3 weeks)
Experimental: Non Surgery Arm
The treatment arm will be comprised of participants not requiring surgery. - Participants will receive treatment with Abemaciclib, twice daily oral at specified dose for 21 day cycle Pembrolizumab intravenous once in 21 day cycle (3 weeks)
Drug: - Pembrolizumab
intravenously over 30 minutes every 21 days (+/- 3 days)
Drug: - Abemaciclib
Oral 2 times a day
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.