Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| BBI608-201GBM | Other Identifier | Boston Biomedical, Inc. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is an open label, multi-center, phase 1 safety run-in and phase 2 study of BBI608 in combination with temozolomide in patients with recurrent or progressive glioblastoma who have not received prior bevacizumab therapy.
In arm A, patients who are candidates for surgical resection will receive BBI608 as monotherapy prior to resection, followed by post-operative BBI608 administered in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, in combination with temozolomide.
In the phase 1/dose-limiting toxicity (DLT) cohort portion of this study, pharmacokinetics will be evaluated for both arms A and B. Pharmacodynamics will be evaluated in all patients who undergo surgical resection.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma. |
|
| Arm B | Experimental | Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BBI608 | Drug | In arm A, BBI608 will be administered at the recommended Phase 2 dose (RP2D) twice daily for 7(±2) days prior to planned surgical resection or biopsy of recurrent GBM. Upon the clinical recovery of the patient and at a time between 15-28 days after surgery, BBI608 will be administered orally, daily, each day of a 28 day cycle in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, each day of a 28 day cycle at the RP2D in combination with temozolomide. |
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting Toxicities (DLTs) | Number of patients who experienced a dose limiting toxicity following a dosing of BBI608 | 28 days after first administration of combination treatment (BBI608+TMZ) |
| Progression Free Survival (PFS)-6 | To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment. | From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, assessed up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS)-12 | To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment. |
Not provided
Major Eligibility Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Laura and Isaac Perlmutter Cancer Center | New York | New York | 10016 | United States | ||
| University of Calgary |
There are no pre-assignment details, study arm was determined at patient enrollment to the study
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Candidates Whom Surgery is Recommended. | BBI608 will be administered at the recommended phase 2 dose (RP2D) twice daily for 7(±2) days prior to planned surgical resection or biopsy of recurrent GBM. Upon the clinical recovery of the patient and at a time between 15-28 days after surgery, BBI608 will be administered orally, daily, each day of a 28 day cycle in combination with temozolomide |
| FG001 | Candidates Whom Surgery is Not Recommended. | Patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, each day of a 28 day cycle at the recommended phase 2 dose (RP2D) in combination with temozolomide |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Candidates Whom Surgery is Recommended. | Candidates who were candidates for repeat surgical resection |
| BG001 | Candidates Whom Surgery is Not Recommended | Candidates who were not candidates for repeat surgical resection |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose-limiting Toxicities (DLTs) | Number of patients who experienced a dose limiting toxicity following a dosing of BBI608 | Up to the first 6 patients whom surgery was and wasn't recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be≥ 80% compliant to assigned dose to qualify for DLT analysis. | Posted | Count of Participants | Participants | 28 days after first administration of combination treatment (BBI608+TMZ) |
|
Every 1-2 weeks from study enrollment until end of treatment. Following last dose, follow-up period of 30 days.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Candidates Whom Surgery is Recommended | Participants whom surgery was recommended and received at least one dose of study medication (BBI608). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Connor Marshall | Sumitomo Dainippon Pharma Oncology | 843-364-8039 | cmarshall@bostonbiomedical.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 9, 2017 | Apr 7, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 6, 2019 | Apr 7, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D005910 | Glioma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
Not provided
Not provided
| ID | Term |
|---|---|
| C000621033 | napabucasin |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Temozolomide | Drug | Temozolomide (TMZ) will be administered orally, once daily, at a dose of 150 mg/m^2 daily on days 1 through 5 of each 28-day study cycle. The dose of temozolomide can be increased to 200 mg/m^2 as per standard TMZ dosing guidelines for patients who complete at least one cycle at 150 mg/m^2. |
|
|
| From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, up to 12 months |
| Overall Survival (OS) | To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection. | From the time of exposure to study drug to death from any cause. If patient discontinued study drug, they were assessed the first 3 months after discontinuation, then every 3 months up to 1 year, then every 6 months thereafter until death. |
| Disease Control Rate (DCR) | To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline. | 4 weeks |
| Overall Response Rate (ORR) | The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria. | 4 weeks |
| Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve | The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method) | On Day 1 and Day 5 after the first dosing, prior to dosing and 1, 2, 3, 5, 5h40m (day 1 only), 6, 7, 8 and 24 hours after first dose of BBI608 |
| Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors | Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors. | At the time of surgical resection |
| Calgary |
| Alberta |
| Canada |
| Princess Margaret Cancer Centre | Toronto | Ontario | Canada |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Smoking | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Candidates Whom Surgery is Not Recommended |
The first 6 patients whom surgery was not recommended that received 28 days of continuous daily administration of BBI608 in combination with TMZ. Patients also had to be ≥ 80% compliant to assigned dose to qualify for DLT analysis. |
|
|
| Primary | Progression Free Survival (PFS)-6 | To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment. | Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients. | Posted | Number | 80% Confidence Interval | percentage of participants | From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, assessed up to 6 months |
|
|
|
| Secondary | Progression Free Survival (PFS)-12 | To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment. | Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients. | Posted | Number | 80% Confidence Interval | percentage of participants | From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, up to 12 months |
|
|
|
| Secondary | Overall Survival (OS) | To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection. | Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients. | Posted | Median | 95% Confidence Interval | months | From the time of exposure to study drug to death from any cause. If patient discontinued study drug, they were assessed the first 3 months after discontinuation, then every 3 months up to 1 year, then every 6 months thereafter until death. |
|
|
|
| Secondary | Disease Control Rate (DCR) | To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline. | Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients. | Posted | Number | 95% Confidence Interval | percentage of patients | 4 weeks |
|
|
|
| Secondary | Overall Response Rate (ORR) | The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria. | Data was only collected and analyzed for arms that enrolled at least 10 evaluable patients. | Posted | Number | 95% Confidence Interval | percentage | 4 weeks |
|
|
|
| Secondary | Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve | The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method) | Candidates for who surgery was and was not recommended that received at least one dose of study drug and had at least one quantifiable concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/ml | On Day 1 and Day 5 after the first dosing, prior to dosing and 1, 2, 3, 5, 5h40m (day 1 only), 6, 7, 8 and 24 hours after first dose of BBI608 |
|
|
|
| Secondary | Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors | Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors. | Candidates whom surgery is either recommended or nor recommended that received 28 days of study drug and provided tissue samples. | Posted | Count of Participants | Participants | At the time of surgical resection |
|
|
|
| 4 |
| 4 |
| 3 |
| 4 |
| 4 |
| 4 |
| EG001 | Candidates Whom Surgery is Not Recommended | Patients who were not candidates for surgical resection and received at least one dose of study medication (BBI608). | 22 | 30 | 5 | 30 | 30 | 30 |
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Pyramidal tract syndrome | Nervous system disorders | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Cerebrospinal fluid leakage | Nervous system disorders | Systematic Assessment |
|
| Aphasia | Nervous system disorders | Systematic Assessment |
|
| Lethargy | Nervous system disorders | Systematic Assessment |
|
| Status epilepticus | Nervous system disorders | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | Systematic Assessment |
|
| Cellulitis | Infections and infestations | Systematic Assessment |
|
| Postoperative wound infection | Infections and infestations | Systematic Assessment |
|
| Wound infection | Infections and infestations | Systematic Assessment |
|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Pyramidal tract syndrome | Nervous system disorders | Systematic Assessment |
|
| Aphasia | Nervous system disorders | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Memory Impairment | Nervous system disorders | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | Systematic Assessment |
|
| Hemianopia homonymous | Nervous system disorders | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Cerebrospinal fluid leakage | Nervous system disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Gait disturbance | General disorders | Systematic Assessment |
|
| Oedema peripheral | General disorders | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Weight decreased | Investigations | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Weight Increased | Investigations | Systematic Assessment |
|
| White blood cell count decreased | Investigations | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
Not provided
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |