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: CDI
Product Code: BAL101553
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: lisavanbulin
CAS Number: 1387574-54-0
Current Sponsor code: BAL101553
Other descriptive name: CDI
Con
Sponsors
Basilea Pharmaceutica International Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older. 2. Patients who have in the Phase 2a dose expansion portion (Simon’s two-stage design): Recurrent, histologically confirmed, GBM with tumor tissue positive for EB1 by IHC as determined by central laboratory testing; eligible are patients with de novo GBM after prior radical chemoradiotherapy or secondary GBM after prior chemotherapy or radiotherapy; patients must be neurologically stable, without progression of neurologic symptoms, within 15 days prior to starting study drug. 3. Phase 2 a dose expansion portion (Simon’s two-stage design): Patients with recurrent glioblastoma must be evaluable per RANO, defined by contrast-enhancing MRI, within 15 days prior to starting study drug. 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). 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 - Post-hysterectomy and/or post-bilateral salpingectomy or ovariectomy. - Congenital or acquired condition that prevents childbearing. - 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 occlusion or vasectomy), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), total heterosexual abstinence. 8. Male patients must agree not to donate sperm from the first dose of study drug until 90 days after the end of treatment. Male patients, without a vasectomy or other conditions resulting in azoospermia and with a partner of childbearing potential, must agree to use condoms during the study and for at least 90 days after the end of treatment. 9. Signed, written informed consent. 10. Patients must be able and willing to comply with the required food intake restrictions. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
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 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 (Phase2a: 2 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. Increase 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 = 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 tac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 2a dose expansion portion (Simon’s two-stage design): To determine the efficacy of daily oral BAL101553 in patients with recurrent GBM whose tumor tissue is positive for end-binding protein 1 (EB1) based on immunohistochemistry (IHC) based on the objective response rate as per RANO criteria. A tissue-screening program adhering to local standards in selected countries will be established to support the identification of potential patients.;Secondary Objective: Phase 2a dose expansion portion (Simon’s two-stage design): - To evaluate the efficacy of BAL101553 based on overall survival (OS), progression-free survival (PFS) and the proportion of patients with PFS at 6 months after start of study drug treatment (PFS6). - To evaluate the safety and tolerability of daily oral BAL101553. - To evaluate BAL101553 and BAL27862 pharmacokinetics (PK).;Primary end point(s): Phase 2a dose expansion portion (Simon’s two-stage design): To determine the efficacy of daily oral BAL101553 in patients with recurrent GBM whose tumor tissue is positive for end-binding protein 1 (EB1) based on immunohistochemistry (IHC) based on the objective response rate as per RANO criteria. A tissue-screening program adhering to local standards in selected countries will be established to support the identification of potential patients.;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. Objective response is assessed during the whole clinical trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall safety endpoints: Type and frequency of AE, SAEs, laboratory, echocardiogram and ECG abnormalities; abnormalities in vital signs, physical examination results, chest X-ray/CT; frequency and causes of study withdrawals and dose modifications. Efficacy endpoints: - Best objective response according to RECIST 1.1 in patients with solid tumors, based on the change from baseline in tumor measurements as measured in patients with measurable disease, and according to RANO criteria in patients with progressive or recurrent GBM or high-grade glioma (Phase 1 only). - Change from baseline in tumor markers (CA-125, PSA) in patients whose disease is characterized by these tumor markers utilizing Rustin criteria for ovarian cancer or PSA Working Group 2 criteria for prostate cancer. - Progression-free survival and OS. Pharmacokinetic assessments (BAL101553 and BAL27862): - Cmax, Tmax, AUC0-t, AUC0-t, AUC0-last, AUC0-8, t½, systemic clearance and volume of distribution. - Total 24 h urinary excretion of BAL101553 and BAL27862. Exploratory endpoints: - Change from baseline in biomarkers (including but not limited to numbers of CTCs, CECs, CEPs).;Timepoint(s) of evaluation of this end point: Safety, tolerability, and anti-tumor activity is assessed during the whole clinical trial. Progression-free survival is assessed for 6 months and OS is assessed at 3-month intervals until death. Phase 2a dose expansion portion (Simon's two-stage design): Pharmacokinetics is assessed at pre-specified time points over 4 weeks in Phase 2a. | — |
Countries
Belgium, Germany, Switzerland, United Kingdom
Contacts
Public ContactMedical Information
Basilea Pharmaceutica International Ltd.
Outcome results
None listed