A Multicenter, Open-Label Study With a Randomized Control Arm of the Efficacy, Safety, and Pharmacokinetics of Intravenously Infused Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme After Failure of Standard First Line Therapy
Overview
- Phase
- Phase 2
- Intervention
- Lomustine
- Conditions
- Glioblastoma Multiforme, Adult
- Sponsor
- CNS Pharmaceuticals, Inc.
- Enrollment
- 252
- Locations
- 67
- Primary Endpoint
- Overall Survival
- Status
- Active, not recruiting
- Last Updated
- 17 days ago
Overview
Brief Summary
This is an open-label, multicenter, randomized, parallel, 2-arm, efficacy and safety study. Patients with GBM after failure of standard first line therapy will be randomized in a 2:1 ratio to receive berubicin or lomustine for the evaluation of OS. Additional endpoints will include response and progression outcomes evaluated by a blinded central reviewer for each patient according to RANO criteria.
A pre-planned, non-binding futility analysis will be performed after approximately 30 to 50% of all planned patients have completed the primary endpoint at 6 months. This review will include additional evaluation of safety as well as secondary efficacy endpoints. Enrollment will not be paused during this interim analysis.
Detailed Description
Berubicin is one of the first anthracyclines that crosses the blood brain barrier and overcomes drug resistance (i.e. it is not a substrate for multi-drug resistant/breast cancer resistant transporters). A Phase 1 clinical trial of berubicin in patients with primary CNS malignancies demonstrated a durable response (one subject alive 13+ years) as well as stable disease in heavily pretreated patients. Therefore, this phase 2 study is designed to further evaluate Berubicin's activity in patients with rGBM after treatment with standard of care.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients will be eligible for the study if they meet all of the following inclusion criteria and none of the
Exclusion Criteria
- •Inclusion criteria
- •Written informed consent from the patient or their legally authorized representative (LAR) prior to any study-related procedure, and willing and able to comply with the protocol and aware of the investigational nature of this study.
- •At least 18 years of age.
- •KPS score of ≥ 60
- •A confirmed GBM diagnosis must be based on local review of tumor tissue from the initial biopsy, surgery, or re-resection. A formal pathology report confirming GBM is acceptable. It is not a requirement for slides to be sent to a central reviewer.
- •Recurrent or progressive GBM as evaluated by central review applying RANO criteria on contrast MRI scans of the Baseline/Screening MRI scan obtained up to six weeks prior to C1D1 and a historical scan taken before the Baseline/Screening scan that meets at least 1 of the following criteria:
- •In the case of measurable disease, progression will be documented by ≥ 25% increase in the sum of the perpendicular diameter products (SPDPs) of the measurable contrast-enhancing (target) lesions or any new measurable lesions.
- •If the SPDPs cannot be reliably estimated due to the lesion's complex conspicuity, shape, and contrast enhancement pattern, the volume of all measurable and non-measurable lesions may be used instead, applying the same threshold (≥ 25% increase) to confirm disease progression.
- •In the case of non-measurable lesions in the historical scan, any transformation into measurable lesions (≥10 mm in both maximum perpendicular diameters) in the Baseline/Screening scan will be evidence of progression.
- •If there are only non-measurable (non-target) lesions in the Baseline/Screening scan, additional lesions/sites will be considered evidence of progression based on the historical scan. Patients with new cerebrospinal fluid (CSF) seeding will not be considered eligible.
Arms & Interventions
Lomustine (CCNU, CeeNU®, or Gleostine®) capsules
Lomustine (CCNU, CeeNU®, or Gleostine®) capsules will be administered at the institutionally-approved dose and regimen or per the full prescribing information/summary of product characteristics.
Intervention: Lomustine
Berubicin
Berubicin intravenously infused will be administered at a dose of 7.1 mg/m2 as free base as a 2 hour intravenous (IV) infusion once daily for 3 consecutive days followed by 18 days off study drug (each cycle = 21 days) Each treatment cycle is 21 days. Subjects will be allowed to continue on treatment at the discretion of the Investigator if there is no evidence of disease progression and the subject is not experiencing unacceptable toxicity as well as if both the subject and Investigator agree that further therapy is in the subject's best interest.
Intervention: Berubicin
Outcomes
Primary Outcomes
Overall Survival
Time Frame: Through study completion an average of 4 years.
To assess the effect of berubicin compared with lomustine on overall survival (OS) in adult patients with GBM that has recurred or progressed after standard initial therapy
Secondary Outcomes
- Overall Response Rate(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics tmax(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics Rac(Through study completion an average of 4 years.)
- Event Free Survival(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics AUC0-tau(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics CL(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics Cmax(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics AUC0-∞(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics Vz(Through study completion an average of 4 years.)
- Progression Free Survival(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics AUC0-last(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics t1/2(Through study completion an average of 4 years.)
- Plasma Pharmacokinetics Css(Through study completion an average of 4 years.)
- Safety of the Recommended Phase 2 Dose of Berubicin(From signing of informed consent until until 28 days after the last dose of berubicin and 42 days after the last dose of lomustine, or until the patient receives any additional therapy for their disease (whichever comes first).)