Phase 1/2a Study of BAL101553 as 48-hour Infusions in Patients With Advanced Solid Tumors or Recurrent Glioblastoma

NCT ID: NCT02895360

Last Updated: 2023-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-24
• Study Completion Date: 2020-08-07

Brief Summary

Single-agent, open-label, multi-center sequential dose escalation and expansion study of BAL101553, administered as an intravenous (IV) infusion over 48 hours to adults with advanced or recurrent solid tumors or recurrent glioblastoma.

Detailed Description

This is the first study of prolonged intravenous infusion of BAL101553 (lisavanbulin). BAL101553 will be administered as an intravenous infusion over 48 hours, to adults with advanced or recurrent solid tumors or recurrent glioblastoma who have failed standard therapy, or for whom no effective standard therapy is available.

The primary goal of the study is to find the highest dose of BAL101553 that can safely be given to humans and to assess what side effects occur. The study will start by treating patients with a low dose. Once it has been shown that this low dose is well tolerated, new patients will be treated at higher dose levels ("dose escalation"). Once the highest, well tolerated dose is identified, up to 20 new patients with platinum-resistant/refractory ovarian cancer and up to 20 new patients with recurrent glioblastoma will be treated at that dose (this part is called "dose expansion") to further assess as secondary goal the tolerability and potential anticancer activity of BAL101553. A further secondary goal of this study is to assess the pharmacokinetics of BAL101553.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1

Fixed 3+3 dose escalation of BAL101553 in patients with advanced solid tumors

Group Type: EXPERIMENTAL

BAL101553

Intervention Type: DRUG

BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; oral capsule daily for one week during Cycle 2 (study days 15-21)

Phase 2a

BAL101553 at MTD in patients with platinum-resistant/refractory ovarian cancer or recurrent glioblastoma

Group Type: EXPERIMENTAL

BAL101553 at MTD

Intervention Type: DRUG

BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; treatment with maximum tolerated dose (MTD)

Interventions

BAL101553

BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; oral capsule daily for one week during Cycle 2 (study days 15-21)

Intervention Type: DRUG

BAL101553 at MTD

BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; treatment with maximum tolerated dose (MTD)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Phase 1: Patients with either histologically or cytologically confirmed advanced or recurrent solid tumor, who failed standard therapy or for whom no effective standard therapy is available.

Phase 2a: Patients with platinum-resistant/refractory ovarian, fallopian tube or primary peritoneal cancer (high-grade serous, endometrioid, or carcinosarcoma histotypes) or glioblastoma in first relapse.

3. Patients with solid tumors must have measurable disease according to Response Evaluation Criteria in Solid Tumors [RECIST] v1.1.

Patients with recurrent glioblastoma must have measurable disease defined by contrast-enhancing magnetic resonance imaging.

4. Life expectancy ≥ 12 weeks

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

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

Exclusion Criteria

1. Patients with 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 glioblastoma 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, or have been treated previously with bevacizumab.

2. Patients who have had prior exposure to BAL101553.

3. Peripheral neuropathy ≥ CTCAE grade 2.

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

5. Systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg at the screening visit.

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

7. Women who are pregnant or breast-feeding. Men or women of reproductive potential who are 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

Locations

Oncology Institute of Southern Switzerland; Ospedale Regionale San Giovanni Bellinzona e Valli

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Cantonal Hospital of Grisons, Department of Oncology/ Haematology

Chur, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Cantonal Hospital of St. Gallen, Dep. Medical Oncology & Hematology

Sankt Gallen, , Switzerland

UniversitaetsSpital Zürich

Zurich, , Switzerland

Countries

Switzerland

References

Joerger M, Hundsberger T, Haefliger S, von Moos R, Hottinger AF, Kaindl T, Engelhardt M, Marszewska M, Lane H, Roth P, Stathis A. Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study. Invest New Drugs. 2023 Apr;41(2):267-275. doi: 10.1007/s10637-023-01336-9. Epub 2023 Feb 16.

Reference Type: DERIVED

PMID: 36792805 (View on PubMed)

Joerger M, Stathis A, Metaxas Y, Hess D, Mantiero M, Mark M, Volden M, Kaindl T, Engelhardt M, Larger P, Lane H, Hafner P, Levy N, Stuedeli S, Sessa C, von Moos R. A Phase 1 study of BAL101553, a novel tumor checkpoint controller targeting microtubules, administered as 48-h infusion in adult patients with advanced solid tumors. Invest New Drugs. 2020 Aug;38(4):1067-1076. doi: 10.1007/s10637-019-00850-z. Epub 2019 Aug 30.

Reference Type: DERIVED

PMID: 31471863 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan

View Document

Other Identifiers

CDI-CS-003

Identifier Type: -

Identifier Source: org_study_id