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

NCT ID: NCT02490800

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-20
• Study Completion Date: 2022-11-24

Brief Summary

First in human, open-label, dose escalation (Phase I) and expansion study (Phase 2a) of oral lisavanbulin (BAL101553) in adult patients with advanced solid tumors and adult patients with recurrent or progressive glioblastoma (GBM) or high-grade glioma (HGG).

Detailed Description

This was the first study of the oral formulation (hard capsules) of lisavanbulin. Lisavanbulin was administered once daily during each day of a 28-day treatment cycle to adults with advanced or recurrent solid tumors or recurrent or progressive GBM / HGG who had failed standard therapy, or for whom no effective standard therapy was available.

In Phase 1, the highest dose of lisavanbulin was determined that could safely be given to adults with advanced or recurrent solid tumors, recurrent or progressive GBM / HGG.

In Phase 2a, the tolerability and potential anticancer activity of oral lisavanbulin was assessed in patients with recurrent GBM whose tumor tissue tests positive for end-binding protein 1 (EB1). The study also measured pharmacokinetics.

Conditions

Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 dose escalation portion

Phase 1 dose escalation portion - an accelerated 3+3 titration design in patients with:

1. advanced or recurrent solid tumors

2. recurrent or progressive GBM / HGG

Group Type: EXPERIMENTAL

Lisavanbulin Phase 1 dose escalation portion

Intervention Type: DRUG

Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily in the dose range of 2 to 35 mg/day

Phase 2a dose expansion portion

Phase 2a expansion portion (Simon's two-stage design) - Patients with recurrent and EB1-positive GBM

Group Type: EXPERIMENTAL

Lisavanbulin Phase 2a expansion portion

Intervention Type: DRUG

Recommended Phase 2 dose (RP2D) of 25 mg/day lisavanbulin hard capsules containing 5 mg study drug was administered once daily.

Interventions

Lisavanbulin Phase 1 dose escalation portion

Lisavanbulin hard capsules, containing 1 mg or 5 mg study drug, were given orally to fasted patients once daily in the dose range of 2 to 35 mg/day

Intervention Type: DRUG

Lisavanbulin Phase 2a expansion portion

Recommended Phase 2 dose (RP2D) of 25 mg/day lisavanbulin hard capsules containing 5 mg study drug was administered once daily.

Intervention Type: DRUG

Other Intervention Names

BAL101553; BAL101553

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Patients who had 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 was available to them

2. histologically-confirmed GBM or HGG, with progressive or recurrent disease after prior radiotherapy, with or without chemotherapy. This also included patients with histologically-confirmed low-grade glioma who presented with unequivocal evidence by imaging of transformation to GBM / HGG

Phase 2a dose expansion portion:

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

3. Phase 1: Patients had to have measurable disease; according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 for patients with advanced or recurrent solid tumors, and per radiological assessment in neuro-oncology (RANO) criteria for patients with recurrent or progressive GBM /HGG. Phase 2a: Patients had to be evaluable per RANO criteria.

4. Life expectancy ≥ 12 weeks

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

6. Patients with advanced solid tumors had to have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 and patients with recurrent or progressive glioblastoma had to have an ECOG performance status ≤ 2

Exclusion Criteria

1. Patients with advanced or recurrent solid tumors who had 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 had not recovered from side effects of prior therapies

Patients with recurrent or progressive GBM / HGG who had: received radiotherapy within 6 weeks (Phase 1) or 12 weeks (Phase 2a), unless there was a new area of enhancement consistent with recurrent tumor outside the radiation field; received administration of prior anti-tumor chemotherapy within 4 weeks, or within 6 weeks for nitrosoureas; undergone surgical resection within 4 weeks (Phase 2a: 2 weeks) or a stereotactic biopsy/core biopsy within 1 week prior to starting study drug;

2. Patients who have had prior exposure to lisavanbulin

3. Inability to swallow oral medication

4. Increase in steroid dose in GBM or HGG 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 was expected to interfere with the oral absorption or tolerance of lisavanbulin

6. Symptomatic brain metastases or leptomeningeal disease, which was indicative of active disease, in patients with advanced or recurrent solid tumors.

7. Peripheral neuropathy ≥ CTCAE grade 2.

8. Uncontrolled intercurrent illness that would have unduly increased 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 were pregnant or breast-feeding. Men or women of reproductive potential who were not willing to apply effective birth control

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Basilea Pharmaceutica

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Kaindl, MD

Role: STUDY_DIRECTOR

Basilea Pharmaceutica International Ltd, Allschwil

Locations

UZ Leuven

Leuven, , Belgium

Klinikum der Goethe-Universität Frankfurt

Frankfurt, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Universitätsspital Basel

Basel, , Switzerland

Inselspital Universitätsspital Bern

Bern, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Universitätsspital Zürich

Zurich, , Switzerland

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, , United Kingdom

Countries

Belgium; Germany; Switzerland; United Kingdom

References

Lopez JS, Haefliger S, Plummer R, Clement PM, Jeffry Evans TR, Laubli H, Roth P, Kristeleit R, Brazil L, Tabatabai G, Wick A, Wunderlich B, Beebe K, Eisner JR, Lane H, Engelhardt M, Kaindl T, Hau P, Hundsberger T, Steinbach J. A phase 1/2a dose-finding study and biomarker assessment of oral lisavanbulin in patients with high-grade glioma or glioblastoma. Cell Rep Med. 2025 Jun 17;6(6):102165. doi: 10.1016/j.xcrm.2025.102165.

Reference Type: DERIVED

PMID: 40532659 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CDI-CS-002

Identifier Type: -

Identifier Source: org_study_id