A Study to Assess CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma

Overview

About this study

The purpose of this study is assess the pharmacokinetics (PK), pharmacodynamics (PD) and Central Nervous System (CNS) penetration of CC-90010 following short-term interval therapy (4 daily doses ) prior to surgery, in subjects with progressive or recurrent WHO Grade II Diffuse Astrocytoma, Grade III Anaplastic Astrocytoma and recurrent Glioblastoma who have failed radiation and chemotherapy, and who are candidates for surgical tumor resection as part of their salvage regimen (planned salvage resection).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Men and women ≥ 18 years of age,) with recurrent or progressive WHO Grade II Diffuse Astrocytoma, Grade III Anaplastic Astrocytoma or recurrent WHO Grade IV Glioblastoma.
  • Subjects must have previously completed standard or a hypofractionated course of radiation therapy and have been exposed to procarbazine, lomustine and vincristine (for Grade II Astrocytoma), including those who have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy, with radiation completed > 12 weeks prior to the first CC-90010 dose (Day 1).
  • Subject must be in first or second recurrence. 
  • Subject must have archival tumor tissue suitable for genetic testing and must give permission to access and test the tissue.
  • Subject is considered an appropriate candidate for surgical resection of the recurrent tumor tissue (salvage resection). 
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1. 
  • Subject must meet laboratory values at screening: 
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without growth factor support for 7 days (14 days if subject received pegfilgrastim);
    • Hemoglobin (Hgb) ≥10 g/dL;
    • Platelet count (plt) ≥150 x 10^9/L;
    • Serum potassium concentration within normal range, or correctable with supplements;
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x Upper Limit of Normal (ULN);
    • Serum total bilirubin ≤ 1.5 x ULN;
    • Serum creatinine ≤ 1.5 x ULN or measured glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2 using an exogenous filtration marker such as iohexol, inulin, 51Cr EDTA or 1 iothalamate, or creatinine clearance of ≥ 50 mL/min using Cockroft-Gault equation;
    • Serum albumin > 3.5 g/dL;
    • PT (or INR) and APTT within normal range.
  • Females and males must agree to contraceptive methods and avoid conceiving throughout study and up to 3 months (females) and 106 days (males) following last dose of CC-90010.

Exclusion Criteria:

  • Subject has received anti-cancer therapy (either approved or investigational) within ≤ 4 weeks (6 weeks for nitrosoureas) or 5 half-lives, whichever is shorter, prior to starting CC-90010. If subject received prior immunotherapy (immune checkpoint inhibitor, vaccine, etc.), a 2 week wash-out is required. For a subject treated with the Optune-TTF device, a 2 day period without use is required.
  • Toxicities resulting from prior chemotherapy, surgery, or radiotherapy must have resolved to ≤ NCI CTCAE (version 5.0) Grade 1 prior to starting CC-90010 treatment (with the exception of Grade 3 alopecia). 
  • Subject has undergone major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to starting CC-90010 or subject who has not recovered from surgery. 
  • Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management, or any other significant GI disorder that could affect the absorption of CC-90010. 
  • Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages. 
  • Evidence of CNS hemorrhage on baseline MRI or CT scan (except for post-surgical, asymptomatic Grade 1 hemorrhage that has been stable for at least 4 weeks). 
  • Subject who requires increasing doses of corticosteroids to treat symptomatic cerebral edema within 7 days of study therapy.
  • Known symptomatic acute or chronic pancreatitis. 
  • Impaired cardiac function or clinically significant cardiac diseases, including any of the following: 
    • LVEF < 45% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO);
    • Complete left bundle branch or bifascicular block;
    • Congenital long QT syndrome;
    • Persistent or clinically meaningful ventricular arrhythmias or atrial fibrillation;
    • QTcF ≥ 480 msec on Screening ECG (mean of triplicate recordings); a marked baseline prolongation of QT/QTc interval, using Fridericia´s QT correction formula;
    • History of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT syndrome;
    • Use of concomitant medications that prolong the QT/QTc interval;
    • Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting CC-90010;
    • Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg). 
  • Pregnant or nursing females. 
  • Known HIV infection. 
  • Known chronic active hepatitis B or C virus (HBV, HCV) infection. 
  • Subject with a requirement for ongoing treatment with therapeutic dosing of anticoagulants or for ongoing prophylactic anticoagulation. Low dose low molecular weight heparin for catheter maintenance is allowed. 
  • History of concurrent second cancers requiring active, ongoing systemic treatment. 
  • Evidence of history of bleeding diathesis. 
  • Subject with known prior episodes of non-arteritic anterior ischemic optic neuropathy (NAION) should be excluded from the study. CC-90010 should be used with caution in subjects with retinitis pigmentosa. 
  • Subject with poor bone marrow reserve as assessed by Investigator such as in the following condition: 
    • Requiring regular hematopoietic support

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Kurt Jaeckle, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions