Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma

Neoplasms Clinical Trial

Official title:

An Open-label Phase 1/2a Study of Oral BAL101553 in Adult Patients With Advanced Solid Tumors and in Adult Patients With Recurrent or Progressive Glioblastoma or High-grade Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02490800
• Other study ID #: CDI-CS-002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 23, 2015
• Est. completion date: November 24, 2022

Study information

• Verified date: December 2022
• Source: Basilea Pharmaceutica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

First in human, open-label, sequential dose escalation and expansion study of oral BAL101553 in adult patients with advanced solid tumors and adult patients with recurrent or progressive glioblastoma or high-grade glioma.

Description:

This is the first study of the oral formulation of BAL101553. BAL101553 will be administered once daily during each day of a 28-day treatment cycle in capsule form to adults with advanced or recurrent solid tumors or recurrent or progressive glioblastoma or high-grade glioma who have failed standard therapy, or for whom no effective standard therapy is available.

In Phase 1, the highest dose of BAL101553 was determined that can safely be given to adults with advanced or recurrent solid tumors, recurrent or progressive glioblastoma or high-grade glioma who have failed standard therapy, or for whom no effective standard therapy is available.

In Phase 2a, the tolerability and potential anticancer activity of oral BAL101553 will be assessed in patients with recurrent glioblastoma whose tumor tissue tests positive for end-binding protein 1 (EB1). The study will also measure pharmacokinetics, pharmacodynamic effects and assess biomarkers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: November 24, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years

2. Patients who have in the

Phase 1 portion either of the following:

1. 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

2. 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.

Phase 2 portion: Recurrent, histologically confirmed, glioblastoma with tumor tissue positive for EB1; eligible are patients with de novo glioblastoma after prior radical chemo-radiotherapy or secondary glioblastoma after prior chemotherapy or radiotherapy.

3. Patients must have measurable disease.

4. Life expectancy = 12 weeks

5. Acceptable organ and marrow function at baseline (protocol defined laboratory parameters)

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. Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

1. Patients with advanced or recurrent solid tumors who have received chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks prior to starting study drug or who have not recovered from side effects of prior therapies.

Patients with recurrent or progressive GBM or high-grade glioma who have: received radiotherapy within 12 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 antitumor 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 BAL1015533.

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 or requirement for > 6 mg/day dexamethasone or equivalent for symptom control.

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

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. Uncontrolled intercurrent illness that would unduly increase the risk of toxicity or limit compliance with study requirements

9. Systolic blood pressure (SBP) = 160 mmHg or diastolic blood pressure (DBP) = 100 mmHg at the screening visit.

10. Blood pressure (BP) combination treatment with more than two antihypertensive medications.

11. Women who are pregnant or breast-feeding. Men or women of reproductive potential who are not willing to apply effective birth control

12. Other protocol-defined exclusion criteria may apply.

Related Conditions & MeSH terms

• Glioblastoma
• Neoplasms

Intervention

Drug:
• Oral daily administration of BAL101553
oral administration

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Germany	Klinikum der Goethe-Universität Frankfurt	Frankfurt
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsklinikum Tübingen	Tübingen
Switzerland	Universitätsspital Basel	Basel
Switzerland	Inselspital Universitätsspital Bern	Bern
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Universitätsspital Zürich	Zürich
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	University College London NHS Foundation Trust	London
United Kingdom	Sir Bobby Robson Cancer Trials Research Centre; Northern Centre for Cancer Care	Newcastle upon Tyne
United Kingdom	Royal Marsden Hospital	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
Basilea Pharmaceutica

Countries where clinical trial is conducted

Belgium,  Germany,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of daily oral BAL101553 based on the number of participants with adverse effects as measure of tolerability at various dose levels		28 day cycles
Primary	Phase 2a: Best objective response according to RANO criteria		28 day cycles
Secondary	Safety and tolerability of daily oral BAL101553 based on the number of participants with adverse events at various dose levels	Incidence of adverse events	28 day cycles
Secondary	Safety and tolerability of daily oral BAL101553 based on the number of participants with safety laboratory changes versus baseline	Incidence of clinically relevant laboratory changes	28 day cycles
Secondary	Safety and tolerability of daily oral BAL101553 based on the number of participants with ECG changes versus baseline	Incidence of clinically relevant ECG changes	28 day cycles
Secondary	Cmax of BAL101553 and BAL27862	Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of BAL101553 and BAL27862	28 day cycles
Secondary	Tmax of BAL101553 and BAL27862	Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of BAL101553 and BAL27862	28 day cycles
Secondary	AUC of BAL101553 and BAL27862	Pharmacokinetic parameter "Area under the plasma concentration versus time curve" AUC of BAL101553 and BAL27862	28 day cycles
Secondary	Half-life of BAL101553 and BAL27862	Pharmacokinetic parameter Half-life of BAL101553 and BAL27862	28 day cycles
Secondary	Anti-tumor activity of daily oral BAL101553 in cancer patients based on RECIST 1.1 -criteria (measurable disease of advanced or recurrent solid tumors).		28 day cycles
Secondary	Anti-tumor activity of daily oral BAL101553 in cancer patients by contrast-enhanced MRI based on RANO criteria (recurrent or progressive GBM or high-grade glioma).		28 day cycles