Advanced or recurrent solid tumors, recurrent or progressive glioblastoma, or high-grade glioma MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BAL101553
Product Code: oral BAL101553
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: lisavanbulin
CAS Number: 1387574-54-0
Current Sponsor code: oral BAL101553
Other descriptiv
Sponsors
Basilea Pharmaceutica International Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting all of the following inclusion criteria at screening will be eligible for enrollment in the study. Informed consent must be obtained within 28 days prior to the start of treatment. Screening evaluations will be performed within 15 days prior to start of treatment (within 35 days for radiology assessments). Patients meeting all of the following: 1. Age 18 years or older. 2. Patients who have either of the following: a. a histologically- or cytologically confirmed advanced or recurrent solid tumor, who failed standard therapy, or for whom no effective standard therapy is available to them b. histologically-confirmed GBM or high-grade glioma, with progressive or recurrent disease after prior radiotherapy, with or without chemotherapy. This will also include patients with histologically-confirmed low-grade glioma who present with unequivocal evidence by imaging of transformation to high-grade glioma/GBM. 3. Patients with advanced solid tumors must have measurable disease (according to Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) documented within 35 days prior to starting study drug, or non-measurable prostate or ovarian cancer that can be followed by prostate specific antigen (PSA) or cancer antigen-125 (CA-125), documented within 15 days prior to starting study drug. Patients with glioblastoma or high-grade glioma must have measurable disease, defined by contrast-enhancing MRI, within 15 days prior to starting study drug. Patients with previous low-grade glioma that progressed after prior radiotherapy (with or without chemotherapy) and are found to have high-grade glioma/GBM by biopsy or imaging are also eligible. 4. Life expectancy = 12 weeks. 5. Acceptable organ and marrow function documented within 15 days prior to starting study drug, defined as follows:* • Absolute neutrophil count = 1.5 × 109/L. • Platelets = 100 × 109/L. • Hemoglobin = 9 g/dL. • Total bilirubin = 1.5 × institutional upper limit of normal (ULN), unless the patient has known Gilbert’s syndrome. • Aspartate amino transferase (AST) and alanine amino transferase (ALT) = 2.5 × institutional ULN or = 5 × ULN in presence of liver metastasis. • Serum creatinine = 1.5 × institutional ULN, or creatinine clearance = 60 mL/min by Cockcroft-Gault formula. • Serum sodium = the institutional lower limit of normal (LLN). * All listed laboratory parameters, and cardiac troponin (see Exclusion criterion 13), must be included in the study-specific pharmacy prescription chart. During the study, all parameters applicable for any study visit must be reviewed by the investigator and the pharmacy prior to dispensing of any study medication. 6. Patients with advanced solid tumors must have an Eastern Cooperative Oncology Group (ECOG) performance status = 1 and patients with recurrent or progressive glioblastoma must have an Eastern Cooperative Oncology Group (ECOG) performance status = 2. 7. Female patients who are not pregnant or breast-feeding and meet one of the following conditions: • Postmenopausal for at least 1 year. • Post-hysterectomy and/or post-bilateral ovariectomy. • Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test result and must use highly effective contraceptive methods for the duration of the study and for an additional 90 days after the last dose of study drug. Highly effective contraceptive methods include male or female sterilization (bilateral tubal occlus
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria at screening must not be enrolled in the study: 1. Patients with advanced or recurrent solid tumors who have received chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks (2 weeks for single fraction of palliative radiotherapy, 6 weeks for nitrosoureas or mitomycin C) prior to starting study drug, or who have not recovered to = Common Terminology Criteria for Adverse Events version 4.03 (CTCAE) grade = 1 from all side effects of prior therapies except for residual toxicities, such as alopecia, which do not pose an ongoing medical risk. • Patients with prostate cancer must have discontinued anti-androgens (e.g., bicalutamide, nilutamide) for at least 6 weeks prior to starting study drug; chemical castration with luteinizing hormone-releasing hormone analogues can be continued. Patients with recurrent or progressive GBM or high-grade glioma who have: received radiotherapy within 6 weeks, unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field, or there is histological confirmation of unequivocal tumor progression; received administration of prior anti-tumor chemotherapy within 4 weeks, or within 6 weeks for nitrosoureas; undergone surgical resection within 4 weeks or a stereotactic biopsy/core biopsy within 1 week prior to starting study drug. 2. Patients who have had prior exposure to BAL101553. 3. Inability to swallow oral medication. 4. Change in steroid dose in GBM or high-grade glioma patients within 5 days prior to first study-drug administration. 5. Patients with gastrointestinal disease or those who have had a procedure that is expected to interfere with the oral absorption or tolerance of BAL101553 (e.g., functionally relevant gastrointestinal obstruction, or frequent vomiting). 6. Symptomatic brain metastases or leptomeningeal disease, indicative of active disease, in patients with advanced or recurrent solid tumors. 7. Peripheral neuropathy = CTCAE grade 2. 8. Known human immunodeficiency virus (HIV) infection. 9. Known acute or chronic hepatitis B or hepatitis C infection. 10. Systolic blood pressure (SBP) = 140 mmHg or diastolic blood pressure (DBP) = 90 mmHg at the screening visit. Patients with an initial clinic BP = 140/90 mmHg may be included if SBP 470 ms on screening electrocardiogram (ECG) or a clinically relevant ECG abnormality. • Congenital long QT syndrome. • History of sustained ventricular tachyc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are to determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of daily oral BAL101553, administered to adults with advanced or recurrent solid tumors who have failed standard therapy, or for whom no effective standard therapy is available, and to patients with recurrent or progressive glioblastoma (GBM) or high-grade glioma.;Secondary Objective: Secondary objectives: • To evaluate the safety and tolerability of daily oral BAL101553. • To evaluate BAL101553 and BAL27862 pharmacokinetics (PK), including the effect of fasted versus fed states. • To assess the anti-tumor activity of daily oral BAL101553 in cancer patients. Exploratory objectives: • To assess the use of biomarkers to characterize pharmacodynamic effects of daily oral BAL101553. • To explore the potential utility of biomarkers in blood and/or tumor tissue as predictive biomarkers.;Primary end point(s): The primary objectives of this study are to determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of daily oral BAL101553, administered to adults with advanced or recurrent solid tumors who have failed standard therapy, or for whom no effective standard therapy is available, and to patients with recurrent or progressive glioblastoma (GBM) or high-grade glioma.;Timepoint(s) of evaluation of this end point: The MTD is determined by DLT assessment. A DLT can occur on any dosing day or at any time thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability, pharmacokinetics, anti-tumor activity;Timepoint(s) of evaluation of this end point: Safety and tolerability is assessed during the whole clinical trial. Pharmacokinetics assessed at prespecified time points on day 1, day 8, day 15 and day 22 during cycle 1 and cycle 2. | — |
Countries
United Kingdom
Contacts
Public ContactMedical Information
Basilea Pharmaceutical International Ltd.
Outcome results
None listed