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

• ClinicalTrials.gov Identifier: NCT02490800
• Recruitment Status: Completed
• First Posted: July 7, 2015
• Last Update Posted: December 13, 2022
• Sponsor: Basilea Pharmaceutica
• Information provided by (Responsible Party): Basilea Pharmaceutica

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Neoplasms	Drug: Oral daily administration of BAL101553	Phase 1; Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 71 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 23, 2015
• Actual Primary Completion Date: September 30, 2022
• Actual Study Completion Date: November 24, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Drug: BAL101553; Oral daily administration of BAL101553	Drug: Oral daily administration of BAL101553; oral administration

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 28 day cycles ]
2. Phase 2a: Best objective response according to RANO criteria [ Time Frame: 28 day cycles ]

Secondary Outcome Measures :

1. Safety and tolerability of daily oral BAL101553 based on the number of participants with adverse events at various dose levels [ Time Frame: 28 day cycles ]
   Incidence of adverse events
2. Safety and tolerability of daily oral BAL101553 based on the number of participants with safety laboratory changes versus baseline [ Time Frame: 28 day cycles ]
   Incidence of clinically relevant laboratory changes
3. Safety and tolerability of daily oral BAL101553 based on the number of participants with ECG changes versus baseline [ Time Frame: 28 day cycles ]
   Incidence of clinically relevant ECG changes
4. Cmax of BAL101553 and BAL27862 [ Time Frame: 28 day cycles ]
   Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of BAL101553 and BAL27862
5. Tmax of BAL101553 and BAL27862 [ Time Frame: 28 day cycles ]
   Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of BAL101553 and BAL27862
6. AUC of BAL101553 and BAL27862 [ Time Frame: 28 day cycles ]
   Pharmacokinetic parameter "Area under the plasma concentration versus time curve" AUC of BAL101553 and BAL27862
7. Half-life of BAL101553 and BAL27862 [ Time Frame: 28 day cycles ]
   Pharmacokinetic parameter Half-life of BAL101553 and BAL27862
8. Anti-tumor activity of daily oral BAL101553 in cancer patients based on RECIST 1.1 -criteria (measurable disease of advanced or recurrent solid tumors). [ Time Frame: 28 day cycles ]
9. 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). [ Time Frame: 28 day cycles ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Belgium

UZ Leuven

Leuven, Belgium, 3000

Germany

Klinikum der Goethe-Universität Frankfurt

Frankfurt, Germany, 60528

Universitätsklinikum Heidelberg

Heidelberg, Germany, 69120

Universitätsklinikum Regensburg

Regensburg, Germany, 93053

Universitätsklinikum Tübingen

Tübingen, Germany, 72076

Switzerland

Universitätsspital Basel

Basel, Switzerland, 4031

Inselspital Universitätsspital Bern

Bern, Switzerland, 3010

Kantonsspital St. Gallen

St. Gallen, Switzerland, 9007

Universitätsspital Zürich

Zürich, Switzerland, 8091

United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

University College London NHS Foundation Trust

London, United Kingdom, NW1 2BU

Sir Bobby Robson Cancer Trials Research Centre; Northern Centre for Cancer Care

Newcastle upon Tyne, United Kingdom, NE7 7DN

Royal Marsden Hospital

Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

Basilea Pharmaceutica

Investigators

• Study Director: Thomas Kaindl, MD; Basilea Pharmaceutica International Ltd

More Information

• Responsible Party: Basilea Pharmaceutica
• ClinicalTrials.gov Identifier: NCT02490800
• Other Study ID Numbers: CDI-CS-002
• First Posted: July 7, 2015
• Last Update Posted: December 13, 2022
• Last Verified: December 2022

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue