Oral BAL101553 in Patients with Advanced Solid Tumors or with Brain Cancer
- Conditions
- Advanced or recurrent solid tumors, recurrent or progressive glioblastoma, or high-grade gliomaMedDRA 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-DE
- Lead Sponsor
- Basilea Pharmaceutica International Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 72
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
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 < 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 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 tac
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method