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

NCT04047303 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: CC-90010-GBM-001U1111-1235-80822019-000241-12
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 4

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).

Conditions

Astrocytoma; Glioblastoma

Keywords

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

Outcome Measures

Primary Outcomes (8)

• Intratumoral concentration of CC-90010 in tumor tissue collected intraoperatively

  Intratumoral concentration of CC-90010 will be summarized using descriptive statistics

  Up to 4 days following C1D1

• Pharmacokinetics - AUC24

  Area under the plasma concentration time-curve

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - AUClast

  Area under the plasma concentration time-curve

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - Cmax

  Maximum observed plasma concentration

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - Tmax

  Time to maximum plasma concentration

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - t1/2

  Terminal half-life

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - CL/F

  Apparent clearance

  At the end of Cycle 1 (each cycle is 28 days)

• Pharmacokinetics - V2/F

  Apparent volume of distribution

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (1)

• Adverse Events (AEs)

  From enrollment until at least 28 days after completion of study treatment

Study Arms (1)

Administration of CC-90010

EXPERIMENTAL

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.

Drug: CC-90010

Interventions

CC-90010 DRUG

CC-90010

Administration of CC-90010

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• 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) ≥100 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 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.

You may not qualify if:

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

Sponsors & Collaborators

• Celgene: lead

Study Sites (4)

Local Institution - 101

Tampa, Florida, 33612, United States

Location

Local Institution - 102

Boston, Massachusetts, 02215, United States

Location

Local Institution - 302

Madrid, 28040, Spain

Location

Local Institution - 301

Madrid, 28041, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Astrocytoma; Glioblastoma; Recurrence

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: August 6, 2019
• Study Start: January 2, 2020
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

ES (2); US (2)