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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04047303
Recruitment Status : Recruiting
First Posted : August 6, 2019
Last Update Posted : July 24, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE July 29, 2019
First Posted Date  ICMJE August 6, 2019
Last Update Posted Date July 24, 2020
Actual Study Start Date  ICMJE January 2, 2020
Estimated Primary Completion Date March 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Intratumoral concentration of CC-90010 in tumor tissue collected intraoperatively [ Time Frame: Up to 4 days following C1D1 ]
    Intratumoral concentration of CC-90010 will be summarized using descriptive statistics
  • Pharmacokinetics - AUC24 [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Area under the plasma concentration time-curve
  • Pharmacokinetics - AUClast [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Area under the plasma concentration time-curve
  • Pharmacokinetics - Cmax [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Maximum observed plasma concentration
  • Pharmacokinetics - Tmax [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Time to maximum plasma concentration
  • Pharmacokinetics - t1/2 [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Terminal half-life
  • Pharmacokinetics - CL/F [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Apparent clearance
  • Pharmacokinetics - V2/F [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Apparent volume of distribution
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
Adverse Events (AEs) [ Time Frame: From enrollment until at least 28 days after completion of study treatment ]
Number of participants with adverse event
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma
Official Title  ICMJE 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
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Astrocytoma
  • Glioblastoma
Intervention  ICMJE Drug: CC-90010
CC-90010
Study Arms  ICMJE Experimental: Administration of CC-90010
During 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.
Intervention: Drug: CC-90010
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 5, 2019)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 24, 2021
Estimated Primary Completion Date March 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04047303
Other Study ID Numbers  ICMJE CC-90010-GBM-001
U1111-1235-8082 ( Other Identifier: WHO )
2019-000241-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Zariana Nikolova, MD, PhD Celgene Corporation
PRS Account Celgene
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP