LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients (NCT04391595) | Clinical Trial Compass
CompletedEarly Phase 1
LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients
United States42 participantsStarted 2020-07-11
Plain-language summary
This trial is an open-label, multicenter, Phase 0/2 trial that will enroll up to 50 participants with recurrent glioblastoma which are schedule for resection. In the lead-in cohort, a total of 10 participants will be enrolled into the proposed phase 0 clinical trial. Participants will be administered LY3214996 plus Abemaciclib prior to surgical resection of their tumor. If positive PK results are demonstrated in ≥50% of Phase 0 participants and at least 5 participants are enrolled into Phase 2, up to approximately 40 additional participants will be enrolled in the dose expansion cohort in order to achieve a total of 25 participants enrolled into Phase 2 (lead-in cohort + dose expansion).
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Prior resection of histologically diagnosed WHO Grade IV glioma defined as glioma participants who have progressed on or following standard (Stupp regimen) therapy, which included maximal surgical resection, temozolomide, and fractionated radiotherapy.
✓. Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI.
✓. Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria.
✓. Sufficient archival tissue available to confirm eligibility.
✓. For gliomas, archival tissue must demonstrate: (a) RB positivity (≥20%) on immunohistochemistry (IHC); or, no RB mutations on next-generation sequencing (NGS), (b) Chromosomal loss of CDKN2A/B/C; or, CDK4/6 amplification on array CGH or NGS, (c) pERK positivity (\>30%) on IHC.
✓. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
✓. Participant has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
What they're measuring
1
Phase 0: Pharmacokinetic analysis of tumor tissue
Timeframe: 8 hour
2
Phase 0: Pharmacokinetic analysis of cerebrospinal fluid (CSF)
Timeframe: 8 hour
3
Pharmacokinetic analysis of plasma
Timeframe: Day 6 at 0, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose
✓. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
Exclusion criteria
✕. Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
✕. Pregnancy or lactation.
✕. Known allergic reactions to components of the abemaciclib or LY3214996.
✕. Active infection or fever \>38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1.
✕. Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis.
✕. Known active systemic 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.
✕. Have history of central or branch retinal artery or venous occlusion with significant vision loss or other retinal diseases that cause current visual impairment or would likely cause visual impairment over the time period of the study.
✕. Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).