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NeoplasmsPhase 1/2NCT02490800

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

A Phase 1/2 study testing Lisavanbulin Phase 1 dose escalation portion and Lisavanbulin Phase 2a expansion portion in people with Neoplasms, run by Basilea Pharmaceutica at 13 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
Lisavanbulin Phase 1 dose escalation portion and Lisavanbulin Phase 2a expansion portion
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
13 sitesin 4 countries
Study dates
20 May 2015to 24 Nov 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Main Inclusion Criteria:

  1. Age ≥ 18 years
  2. Patients who had in the Phase 1 portion either of the following:
  3. 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
  4. 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.
  5. 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.
  6. Life expectancy ≥ 12 weeks
  7. Acceptable organ and marrow function at baseline (protocol defined laboratory parameters)
  8. 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

Main 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

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

Germany4 sites

  • Klinikum der Goethe-Universität Frankfurt

    Frankfurt, 60528

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • Universitätsklinikum Tübingen

    Tübingen, 72076

Other trials in Germany

Switzerland4 sites

  • Universitätsspital Basel

    Basel, 4031

  • Inselspital Universitätsspital Bern

    Bern, 3010

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • Universitätsspital Zürich

    Zurich, 8091

Other trials in Switzerland

United Kingdom4 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • University College London NHS Foundation Trust

    London, NW1 2BU

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

    Newcastle upon Tyne, NE7 7DN

  • Royal Marsden Hospital

    Sutton, SM2 5PT

Other trials in United Kingdom

Belgium1 site

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

About this study

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

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).

Read the 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
Being tested
Lisavanbulin Phase 1 dose escalation portion, Lisavanbulin Phase 2a expansion portion
Keywords
Advanced solid tumors, Recurrent glioblastoma, High-grade glioma
Medical subject headings
Neoplasms, Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lisavanbulin Phase 1 dose escalation portionDrug

    Also called BAL101553

    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

  • Lisavanbulin Phase 2a expansion portionDrug

    Also called BAL101553

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

Study groups in NCT02490800
Study groupRoleWhat they receive
Phase 1 dose escalation portionExperimentalPhase 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
Receives: Drug: Lisavanbulin Phase 1 dose escalation portion
Phase 2a dose expansion portionExperimentalPhase 2a expansion portion (Simon's two-stage design) - Patients with recurrent and EB1-positive GBM
Receives: Drug: Lisavanbulin Phase 2a expansion portion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin

    First 28-day treatment cycle dose limiting toxicities (DLT) graded according to Common Terminology Criteria for Adverse Events (CTCAE) in the MTD-determining population in Phase 1 based on the number of participants with adverse effects as measure of tolerability at various dose levels

    Measured: During first 28 day cycle

  2. Phase 2a: Best Objective Response

    The best objective response was calculated as the proportion of patients responding (i.e., with a best observed objective response of complete or partial response) based on "radiological assessment in neuro-oncology (RANO)" criteria

    Measured: Until the study discontinuation, on average 161 days (maximum of 381 days)

  3. Phase 2a: Objective Response Rate (ORR)

    The ORR was calculated as the percentage of patients (rate) with complete and partial responses and its 95% Confidence Interval (CI) based on RANO criteria

    Measured: Until the study discontinuation, on average 161 days (maximum of 381 days)

Secondary outcomes (9)

  1. Number of Patients With CTCAE Grade 3-4 TEAEs

    Number of patients experiencing treatment-emergent adverse events (TEAE) of CTCAE Grade 3 or 4

    Measured: TEAEs were defined as all events occurring after lisavanbulin treatment began and up to 28 days after last study drug administration which corresponded to a maximum of 1653 days (4,5 years)

  2. Cmax of Avanbulin (BAL27862)

    Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of avanbulin Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862)

    Measured: Plasma PK profiles were obtained on Cycle 1, Day 1 and on Cycle 2, Day 1 (pre-dose and from 0 up to 24 h post-dose) for all patients in the Phase 1 study who received lisavanbulin. For Phase 2 a study, PK parameters were obtained only on Cycle 1, Day 1

  3. Tmax of Avanbulin (BAL27862)

    Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of avanbulin (BAL27862) Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).

    Measured: Plasma PK profiles were obtained on Cycle 1, Day 1 and on Cycle 2, Day 1 (pre-dose and from 0 up to 24 h post-dose) for all patients in the Phase 1 study who received lisavanbulin. For Phase 2 a study, PK parameters were obtained only on Cycle 1, Day 1

  4. AUC of Avanbulin (BAL27862)

    Pharmacokinetic parameter "Area under the plasma concentration versus time curve" AUC of avanbulin (BAL27862) Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).

    Measured: Plasma PK profiles were obtained on Cycle 1, Day 1 and on Cycle 2, Day 1 (pre-dose and from 0 up to 24 h post-dose) for all patients in the Phase 1 study who received lisavanbulin. For Phase 2 a study, PK parameters were obtained only on Cycle 1, Day 1

  5. Phase 1: Best Objective Response

    The best objective response was calculated as the proportion of patients responding (i.e., with a best observed objective response of complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 for patients with advanced or recurrent solid tumors); and based on RANO criteria for patients with recurrent or progressive GBM / HGG

    Measured: Until the end of treatment, on average 151 days (maximum of 1653 days), every other 28 day cycle

  6. Phase 1: Objective Response Rate (ORR)

    The ORR was calculated as the percentage of patients (rate) with complete and partial responses and its 95% CI based on RECIST criteria v1.1 for patients with advanced or recurrent solid tumors; and based on RANO criteria for patients with recurrent or progressive GBM / HGG

    Measured: Until the study discontinuation, on average 151 days (maximum 1653 days), every other 28 day cycle

  7. Phase 2a: PFS

    PFS was defined as the interval between the date of drug administration and the earliest date of objective disease progression based on RANO criteria for patients with recurrent or progressive GBM / HGG. Patients who have not progressed or died at the end of the study were censored at the time of their latest objective tumor assessment.

    Measured: 1 year

  8. Phase 2a: PFS at 6 Months

    Percentage of patients without disease progression based on RANO criteria 6 months after the start of treatment. The values were determined using the Kaplan-Meier and Brookmeyer-Crowley methods.

    Measured: 6 months

  9. Phase 2a: Overall Survival (OS) at 12 Months

    Percentage of patients alive 12 months after the start of treatment. The values were determined using the Kaplan-Meier and Brookmeyer-Crowley methods.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jul 2015 (estimated)
  2. Study start20 May 2015
  3. Primary completion30 Sep 2022
  4. Study completion24 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02490800
Sponsor's protocol ID
CDI-CS-002
Status last verified
Jun 2024
First submitted
25 Jun 2015
Last updated
26 Jun 2024
Data monitoring committee
No

Publications

  • 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.

    PubMed 40532659

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lisavanbulin Phase 1 dose escalation portion and Lisavanbulin Phase 2a expansion portion in people with Neoplasms, run by Basilea Pharmaceutica at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Germany, Switzerland, United Kingdom, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin (time frame: During first 28 day cycle). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02490800, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2024.

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