Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Glioma

Brain Neoplasms

Gliosarcoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Proteasome Inhibitors

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Part1-Phase1: MRZ 10 minute IV infusion on Days 1, 8, and 15 plus BEV IV infusion on Days 1 and 15 of each 28-day cycle.

Part2-Phase2: MRZ 10 minute IV infusion administered on Days 1, 8, and 15 of each 28-day cycle.

Part3-Phase2: All subjects will receive IV MRZ infusion and IV BEV infusion. MRZ will be administered as a 10-minute, IV infusion on Days 1, 8, and 15 of every 28-day cycle using intra-patient dose escalation. Starting dose will be 0.8 mg/m2.

Part4- Phase1: All subjects will receive MRZ enterally by NG tube as a bolus on Days 1, 8 and 15 of the first 28-day cycle and BEV IV infusion on Day 15 of the first 28-day cycle. For subsequent 28-day treatment cycles, MRZ will be administered as an IV at the recommended dose and schedule determined in Part 1, with BEV IV on Days 1 and 15.

Part5-Phase1: All subjects will receive IV MRZ infusion and IV BEV infusion. MRZ will be administered as a 10-minute, IV infusion at 0.8 mg/m2 on Days 1, 8, and 15 of every 28-day cycle 0.8 mg/m2

MRZ dosing in Phase 1 to range from 0.55 to 0.8 mg/m2. Dose Escalation: MRZ dose-escalation will occur using a standard 3+3 study design.

The RP2D of MRZ (0.8.mg/m2) will be used in a two stage design, with fifteen response-evaluable patients entered in the first stage. If 1 or more responses are observed at the MRZ RP2D, then the second stage will be implemented with an additional 15 response-evaluable patients treated.

BEV 10 mg/kg IV infusion administered for all cohorts in Phase 1 only.

Ileana Elias, MD

This is a Phase 1/2 clinical trial to evaluate a new combination of drugs, marizomib (MRZ) and bevacizumab (BEV; Avastin®), for the treatment of WHO Grade IV malignant glioma. The study population includes subjects who are in first or second relapse and who have not previously received any bevacizumab or other anti-angiogenic agent or proteasome inhibitor for treatment of malignant glioma. Part 1 Phase 1 evaluates the combination of MRZ and BEV, while Part 2 Phase 2 evaluates single-agent MRZ. Part 3 (Phase 2) includes a combination MRZ using intra-patient dose escalation, and BEV at a fixed dose. Part 4 Phase 1 evaluates MRZ through enteral administration, and BEV at a fixed dose. Part 5 Phase 1 evaluates the repeat-dose pharmacokinetics of MRZ administered IV with ECG.

One of the few treatment options currently FDA approved for recurrent WHO Grade IV malignant glioma is BEV. Additional treatment options are needed for these subjects. Published literature indicates that targeting the proteasome in glioma cells has shown significant anti-tumor activity.

MRZ is a novel, second generation proteasome inhibitor that prevents the breakdown of proteins involved in signal transduction which blocks growth and survival of cancer cells. In-vitro studies of multiple glioma cell lines were highly sensitive to MRZ. MRZ had relatively little effect on neural stem/progenitor cells suggesting minimal neurotoxicity while significantly affecting both malignant glioma stem cells and glioma cell lines.

Parts 1 and 2 of this trial have been completed with the Recommended Part 3 (Phase 2) Dose established at 0.8 mg/m2. Part 3 of this trial is enrolling at the MRZ RP2D determined in Phase 1 to assess the combination of MRZ and BEV activity and safety.

Parts 1, 2, 3 and 4 of this trial have been completed with the Recommended Dose established at 0.8 mg/m2. Part 5 of this trial is enrolling.

Stage 1: Marizomib + Bevacizumab in WHO Gr IV GBM; Stage 2: Marizomib Alone; Stage 3: Combination of Marizomib and Bevacizumab

Phase 1, Multicenter, Open-label, Dose-escalation, Combination Study of Marizomib and Bevacizumab in Bevacizumab-Naïve Subjects With WHO Grade IV Malignant Glioma Followed by Phase 2 Studies of Single Agent Marizomib and Combination Marizomib and Bevacizumab, and Phase 1 Dose-Escalation Study of Enterally-administered Marizomib With Bevacizumab

Radiographic ORR is defined as the percentage of participants achieving a Complete Response (CR) or Partial Response (PR), as assessed by the investigator, according to RANO 2010 criteria.

Tumor response assessment was conducted every 2 cycles of study therapy. 95% confidence interval from exact binomial distribution (Clopper-Pearson method).

OS is defined as time from the date of the first dose of study drug to date of death due to any cause. Participants who are alive will be censored at the last follow up visit

Number of subjects experiencing at least 1 Treatment-Emergent Adverse Event (TEAE) within the timeframe specified.

For Part 4, data are presented separately for Cycle 1 (when Marizomib was enterally-administered) and for Cycles 2 and subsequent cycles (when Marizomib was administered IV)

Number of subjects experiencing at least 1 Serious Adverse Event (SAE) within the timeframe specified.

For Part 4, data are presented separately for Cycle 1 (when Marizomib was enterally-administered) and for Cycles 2 and subsequent cycles (when Marizomib was administered IV)

Number of subjects experiencing at least 1 DLT event within the timeframe specified.

DLT is defined as the occurrence of any of the following AEs related to one of the drugs or the combination observed during Cycle 1, using NCI-CTCAE (v 4.03):

* ≥ Grade 3 thrombocytopenia or Grade 2 thrombocytopenia with bleeding.
* Grade 4 neutropenia or anemia lasting for more than 4 days.
* Febrile neutropenia.
* Any ≥ Grade 2 neurological event lasting more than 4 days.
* Grade 3 or 4 non-hematologic toxicity (excluding alopecia), lasting for more than 4 days despite adequate supportive therapy or preventing the next scheduled dose from being administered within 4 days of scheduled day; for ≥ Grade 3 fatigue to be considered a DLT, it must be present for more than 7 days.

For Part 4, data are presented separately for Cycle 1 (when Marizomib was enterally-administered) and for Cycles 2 and subsequent cycles (when Marizomib was administered IV).

DLT was assessed only for Part 1 and Part 4 cohorts.

Number of subjects experiencing at least 1 DLAE within the timeframe specified.

DLAEs are defined as Marizomib-related AEs observed which are:

* related to disturbances in the cerebellum (ie, ataxia, dizziness, dysarthria, fall, gait disturbances) plus hallucinations of any grade
* any other AEs of Grade ≥ 2. DLAEs were assessed only for Part 3 cohorts.

Radiographic ORR is defined as the percentage of participants achieving a Complete Response (CR) or Partial Response (PR), as assessed by the investigator, according to RANO 2010 criteria.

Tumor response assessment was conducted every 2 cycles of study therapy. 95% confidence interval from exact binomial distribution (Clopper-Pearson method).

Radiographic ORR was assessed for Part 1 and Part 3 cohorts

PFS is defined as the time between start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurs first. Disease progression will be determined using RANO 2010 criteria as assessed by the investigator.

PFS was determined using Kaplan-Meier product-limit estimates.

Triphase

Celgene

Marizomib 0.55 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle

Part 1 Cohort 1

Marizomib 0.7 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle

Part 1 Cohort 2

Marizomib 0.8 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle.

MTD = Maximum Tolerated Dose

Part 1 MTD + Dose Expansion Cohort

Marizomib 0.8 mg/m2 on Days 1, 8, and 15 of each 28-day cycle

Part 2 Cohort

Marizomib 0.8 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. Based on presence of dose-limiting adverse events, participants did not escalate Marizomib to a dose of 1.0 mg/m2

Part 3 Cohort 1

Marizomib 0.8 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. Based on lack of dose-limiting adverse events for at least 1 cycle, participants were allowed to escalate Marizomib to a dose of 1.0 mg/m2

Part 3 Cohort 2

Marizomib 0.075 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 1

Marizomib 0.225 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 2

Marizomib 0.675 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 3

Marizomib 1.0 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 4

Marizomib 1.35 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 5

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

All treated participants in Part 2 Cohort

Radiographic Objective Response Rate (ORR) - Part 2 Cohort

Overall Survival (OS) - Part 3 Cohorts

Marizomib 0.075 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 1 - Cycle 1

Marizomib 0.225 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 2 - Cycle 1

Marizomib 0.675 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 3 - Cycle 1

Marizomib 1.0 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 4 - Cycle 1

Marizomib 1.35 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 5 - Cycle 1

Marizomib at different dosage IV-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle

Part 4 All Cohorts - Cycles 2 and Subsequent

Number of Participants Experiencing Adverse Events

Number of Participants Experiencing Serious Adverse Events (SAEs)

All treated participants in Part 1 and Part 4

Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

Number of Participants Experiencing Dose-Limiting Adverse Events (DLAEs)

All treated participants with available measurements

Radiographic Objective Response Rate (ORR)

Progression Free Survival (PFS)

Overall Survival (OS)

Overall Study

Symptoms and General Pathology

Recurrence

Open the BBB using focused ultrasound and microbubble

NaviFUS System

Lumason

An anti-angiogenic agent to block tumor growth

Sheang-Tze Fung, Ph.D.

Arthur Lung, Ph.D.

Jason Sheehan, M.D., Ph.D.

This will be a prospective, open-label, single-arm pilot study to investigate the safety and efficacy of Bevacizumab (BEV) in combination with microbubble (MB)-mediated FUS in patients with recurrent GBM. BEV represents the physician's best choice for the standard of care (SoC) in rGBM after previous treatment with surgery (if appropriate), standard radiotherapy with temozolomide chemotherapy, and with adjuvant temozolomide.

The study aims to demonstrate the high safety profile and effectiveness of BEV+FUS-MB targeted therapy for brain tumors.

Any patient with a histological diagnosis of GBM who meets all of the specific eligibility criteria may participate in this study by signing informed consent in person or through their legal representative. Eligible patients will undergo a 2-week baseline observation screening period.

Up to 10 eligible patients will be enrolled in this study. Eligible patients will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes). After at least 30 minutes, patients will be administered microbubbles (MB) (Lumason®) at a dose of 0.1 mL/kg, along with optimal ultrasound exposure doses determined by the acoustic emission feedback FUS power control algorithm of the NaviFUS System. The treatment will be administered every 2 weeks up to 34 weeks or until evidence of progression disease (PD), intolerable toxicity precluding further treatment, non-compliance with study follow-up, or withdrawal of consent, whichever occurs first.

Safety and Efficacy of Bevacizumab in Combination With NaviFUS System for the Treatment of Recurrent Glioblastoma Multiforme (rGBM)

A Prospective, Open-Label, Single-Arm Pilot Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With NaviFUS System for the Treatment of Recurrent Glioblastoma Multiforme (rGBM)

The incidence and severity of AEs associated with FUS-MB+BEV treatment in patients with rGBM

PFS-6 is the proportion of patients who remain progression-free at the 6-month time point, as determined by Response Assessment in Neuro-Oncology (RANO) Criteria, from the time of their first treatment.

PFS is defined as the time from the date of first treatment to the earliest date of the first objective documentation of radiographic progression disease based on RANO Criteria, death, or last known follow-up due to any cause whichever occurs first. PFS will be followed continuously till the End-of-Study.

One-year survival rate is the proportion of patients who remain alive at the one-year time point from the time of their first treatment.

OS is defined as the time from the date of first treatment to the earliest date of death or last known follow-up due to any cause whichever occurs first. OS will be followed continuously while subjects are on study and via phone interviews every 3 months during the survival follow-up phase of the study.

ORR is defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) based on a combination of imaging and clinical features as assessed by the RANO Criteria.

CBR is defined as the proportion of patients who achieved an overall response of CR, PR, or SD based on a combination of imaging and clinical features as assessed by the RANO Criteria.

Local disease control is defined as the proportion of patients who achieved a CR, PR, or SD within the planning target tumor lesion, as assessed by the RANO Criteria.

Changes in corticosteroid usage will be compared to baseline.

The standardized and validated European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) and brain cancer questionnaire (QLQ-BN20, assessment specific to brain neoplasm) will be assessed at baseline and throughout treatment period. The changes in QoL during treatment will be compared to baseline. QoL is assessed based on the cancer or brain tumor patient's subjective evaluation of their current status, the presence or absence of the specific symptoms, and their overall general health.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Stage 1: Marizomib + Bevacizumab in WHO Gr IV GBM; Stage 2: Marizomib Alone; Stage 3: Combination of Marizomib and Bevacizumab	NCT02330562	Malignant Gliom... Glioblastoma	MRZ BEV	18 Years -	Celgene
Safety and Efficacy of Bevacizumab in Combination With NaviFUS System for the Treatment of Recurrent Glioblastoma Multiforme (rGBM)	NCT06329570	Glioblastoma Mu... Glioblastoma Glioma Brain Tumor Neoplasms Neoplasms, Nerv...	NaviFUS System Lumason Bevacizumab	18 Years -	NaviFUS Corporation

Spots Global Cancer Trial Database for bev

Every month we try and update this database with for bev cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bev

Every month we try and update this database with for bev cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bev cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.