Oral BAL101553 in Patients with Advanced Solid Tumors or with Brain Cancer

Phase 1

• Conditions: Advanced or recurrent solid tumors, recurrent or progressive glioblastoma, or high-grade glioma; MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003371-34-GB
• Lead Sponsor: Basilea Pharmaceutica International Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-10-24
• Last Update Posted: 29 April 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 92

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

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 < 140 mmHg and DBP < 90 mmHg is confirmed in two subsequent BP measurements on the same day, or if subsequent daytime average from ABPM is SBP < 130 mmHg and DBP < 85 mmHg.
11. Blood pressure (BP) combination treatment with more than two antihypertensive medications.
12. Any history of cerebral hemorrhage, cerebral aneurysm, or ischemic stroke; or a history of transient ischemic attack within 24 months prior to screening in patients with advanced or recurrent solid tumors.
Acute intratumoral hemorrhage in patients with recurrent or progressive GBM or high-grade glioma, considered by the study Investigator to be clinically significant.
• Patients with MRI or CT demonstrating old hemorrhage or subacute bleed after a neurosurgical procedure (biopsy or resection) will be eligible for treatment.
13. Significant cardiac disease or abnormality, including any one of the following:
• Left ventricular ejection fraction < 50% at screening (assessed by echocardiography).
• QTcF > 470 ms on screening electrocardiogram (ECG) or a clinically relevant ECG abnormality.
• Congenital long QT syndrome.
• History of sustained ventricular tachyc

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified