Clinical Trials /

CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma

NCT04047303

Description:

CC-90010-GBM-001 is a multi-center, open-label study to assess the pharmacokinetics (PK), pharmacodynamics (PD) and 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).

Related Conditions:
  • Anaplastic Astrocytoma
  • Diffuse Astrocytoma
  • Glioblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma
  • Official Title: A Phase 1, Open-label Study to Assess the Pharmacokinetics, Pharmacodynamics and Central Nervous System (CNS) Penetration of CC-90010 in Preoperative Subjects With Progressive or Recurrent Who Grade II Diffuse Astrocytoma, Grade III Anaplastic Astrocytoma and Recurrent Glioblastoma Scheduled for Resection

Clinical Trial IDs

  • ORG STUDY ID: CC-90010-GBM-001
  • SECONDARY ID: U1111-1235-8082
  • SECONDARY ID: 2019-000241-12
  • NCT ID: NCT04047303

Conditions

  • Astrocytoma
  • Glioblastoma

Interventions

DrugSynonymsArms
CC-90010Administration of CC-90010

Purpose

CC-90010-GBM-001 is a multi-center, open-label study to assess the pharmacokinetics (PK), pharmacodynamics (PD) and 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).

Trial Arms

NameTypeDescriptionInterventions
Administration of CC-90010ExperimentalDuring the preoperative period, all subjects will be given a course of orally administrated CC-90010 at 30 mg once daily for 4 consecutive days on Cycle 1 Day 1 to Day 4. The last CC-90010 dose (Day 4) will be administrated 6-24 hours prior to brain tumor resection. Following recovery from surgery and a minimum of 4 weeks from the first CC-90010 dose (Cycle 1 Day 1), subjects who are fit to continue study treatment my restart CC-90010 on Day 1 of Cycle 2 at 45 mg given orally once daily for 4 consecutive days followed by 24 consecutive days off (4 days on/24 days off), in each 28 day cycle.
  • CC-90010

Eligibility Criteria

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. 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 .

          2. 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).

          3. Subject must be in first or second recurrence.

          4. Subject must have archival tumor tissue suitable for genetic testing and must give
             permission to access and test the tissue.

          5. Subject is considered an appropriate candidate for surgical resection of the recurrent
             tumor tissue (salvage resection).

          6. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.

          7. Subject must meet laboratory values at screening:

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7
                  days (14 days if subject received pegfilgrastim).

               -  Hemoglobin (Hgb) ≥10 g/dL

               -  Platelet count (plt) ≥150 x 109/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 m2 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

          8. 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:

        The presence of any of the following will exclude a subject from enrollment:

          1. 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.

          2. 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).

          3. 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.

          4. 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.

          5. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly
             those with a history of and/or risk of perforation and GI tract hemorrhages.

          6. 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).

          7. Subject who requires increasing doses of corticosteroids to treat symptomatic cerebral
             edema within 7 days of study therapy.

          8. Known symptomatic acute or chronic pancreatitis.

          9. 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).

         10. Pregnant or nursing females.

         11. Known HIV infection.

         12. Known chronic active hepatitis B or C virus (HBV, HCV) infection.

         13. 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.

         14. History of concurrent second cancers requiring active, ongoing systemic treatment.

         15. Evidence of history of bleeding diathesis.

         16. 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.

         17. Subject with poor bone marrow reserve as assessed by Investigator such as in the
             following condition:

               -  Requiring regular hematopoietic support
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Intratumoral concentration of CC-90010 in tumor tissue collected intraoperatively
Time Frame:Up to 4 days following C1D1
Safety Issue:
Description:Intratumoral concentration of CC-90010 will be summarized using descriptive statistics

Secondary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From enrollment until at least 28 days after completion of study treatment
Safety Issue:
Description:Number of participants with adverse event

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Diffuse Astrocytoma
  • Anaplastic Astrocytoma
  • Glioblastoma
  • CC-90010
  • CNS
  • 2nd line or relapsed

Last Updated

August 5, 2019