NeoplasmsPhase 1/2NCT02895360
Phase 1/2a Study of BAL101553 as 48-hour Infusions in Patients With Advanced Solid Tumors or Recurrent Glioblastoma
A Phase 1/2 study testing BAL101553 and BAL101553 at MTD in people with Neoplasms, run by Basilea Pharmaceutica at 6 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- BAL101553 and BAL101553 at MTD
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 6 sitesSwitzerland
- Study dates
- 24 Aug 2016to 7 Aug 2020
- 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
Who may be able to join
- Age ≥ 18 years
- 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.
- 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.
- Life expectancy ≥ 12 weeks
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- Acceptable organ and marrow function at baseline (protocol defined laboratory parameters)
- 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.
- Other protocol-defined inclusion criteria may apply.
Who cannot join
- 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.
- Patients who have had prior exposure to BAL101553.
- Peripheral neuropathy ≥ CTCAE grade 2.
- Uncontrolled intercurrent illness that would unduly increase the risk of toxicity or limit compliance with study requirements
- Systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg at the screening visit.
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- Blood pressure (BP) combination treatment with more than two antihypertensive medications.
- Women who are pregnant or breast-feeding. Men or women of reproductive potential who are not willing to apply effective birth control.
- Other protocol-defined exclusion criteria may apply.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Switzerland6 sites
Oncology Institute of Southern Switzerland; Ospedale Regionale San Giovanni Bellinzona e Valli
Bellinzona, 6500
Inselspital Bern
Bern, 3010
Cantonal Hospital of Grisons, Department of Oncology/ Haematology
Chur, 7000
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011
Cantonal Hospital of St. Gallen, Dep. Medical Oncology & Hematology
Sankt Gallen, 9007
UniversitaetsSpital Zürich
Zurich, 8091
About this study
Official title: An Open-label Phase 1/2a Study of BAL101553 Administered as Intravenous 48-hour Infusions in Adult Patients With Advanced Solid Tumors or Recurrent Glioblastoma
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.
Read the 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
- Being tested
- BAL101553, BAL101553 at MTD
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAL101553Drug
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)
BAL101553 at MTDDrug
BAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; treatment with maximum tolerated dose (MTD)
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | Fixed 3+3 dose escalation of BAL101553 in patients with advanced solid tumors Receives: Drug: BAL101553 |
| Phase 2a | Experimental | BAL101553 at MTD in patients with platinum-resistant/refractory ovarian cancer or recurrent glioblastoma Receives: Drug: BAL101553 at MTD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of BAL101553
First 28-day treatment cycle dose limiting toxicities (DLT) graded according to 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: 28 day cycle
Secondary outcomes (6)
Safety and Tolerability of BAL101553 Treatment Based on Number of Patients With Related Treatment-emergent Adverse Events (TEAEs) in the Phase 1 and Phase 2a Safety Population at Various Dose Levels and Indication
TEAEs are defined as all events occurring after BAL101553 treatment begins, up to 28 days after last study drug administration according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Measured: TEAEs with onset on or after Day 1 of the study and until 28 days after the last dose
AUC of BAL101553 and BAL27862
Pharmacokinetic parameter "Area under the plasma concentration versus time curve" AUC0-last (of BAL101553 and BAL27862 has been assessed after a 48-hour IV infusion.
Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).
Measured: 0 to 168 hours post-dose at Day 1 of Cycle 1 and Cycle 2 in each cohort in Phase 1, 28-day cycles
Cmax of BAL101553 and BAL27862
Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of BAL101553 and BAL27862.
Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862).
Measured: Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.
Tmax of BAL101553 and BAL27862
Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of BAL101553 and BAL27862
Measured: Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.
Bioavailability of Daily Oral BAL101553 Measured by BAL27862 in Phase 1
Ratio of AUCs of avanbulin after oral and IV administration (relative bioavailability) of BAL101553 (lisavanbulin) which is the prodrug of avanbulin (BAL27862)
Measured: Relative oral bioavailability, calculated as dose-normalized AUC0-τ following oral administration on Cycle 2 Day 21 divided by dose normalized AUC0-∞ following IV administration on Cycle 1 Day 1 for each cohort.
Anti-tumor Activity of BAL101553 by Best Response Rate Per RECIST / RANO Criteria
The objective response rate (ORR) was calculated using the efficacy evaluable populations (EEPs in Phase 2a) and the full analysis population (FAP in Phase 1 and Phase 2a) based on RECIST v1.1 guidelines (defines criteria for the radiological assessment in tumor response) for patients with solid tumors (excluding GBM (glioblastoma)) and RANO criteria (assessment Incorporating MRI and clinical factors) for patients with GBM.
ORR = Rate of complete and partial responses
Measured: 28 day cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2016 (estimated)
- Study start24 Aug 2016
- Primary completion7 Aug 2020
- Study completion7 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Basilea Pharmaceutica
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Kaindl, MD, Study director, Basilea Pharmaceutica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02895360
- Sponsor's protocol ID
- CDI-CS-003
- Status last verified
- May 2023
- First submitted
- 5 Sep 2016
- Last updated
- 10 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 36792805Joerger 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.
PubMed 31471863
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase 1/2a Study of BAL101553 Administered as Intravenous 48-hour Infusions in Adult Patients With Advanced Solid Tumors or Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT02895360
- Acronym / sponsor ID
- CDI-CS-003
- Conditions
- Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Basilea PharmaceuticaIndustry (pharma, biotech, devices)
- Study start
- 24 Aug 2016 (actual)
- Primary completion
- 7 Aug 2020 (actual)
- Study completion
- 7 Aug 2020 (actual)
- First posted
- 9 Sep 2016 (estimated)
- Results
- Posted 11 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: BAL101553Fixed 3+3 dose escalation of BAL101553 in patients with advanced solid tumors |
| Phase 2a | Experimental | Drug: BAL101553 at MTDBAL101553 at MTD in patients with platinum-resistant/refractory ovarian cancer or recurrent glioblastoma |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years
- 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.
- 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.
Key exclusion criteria (9 listed)
- 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.
- Patients who have had prior exposure to BAL101553.
- Peripheral neuropathy ≥ CTCAE grade 2.
- Uncontrolled intercurrent illness that would unduly increase the risk of toxicity or limit compliance with study requirements
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAL101553BAL101553 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) | Drug | Phase 1 |
| BAL101553 at MTDBAL101553 48-hour infusion on day 1, 8, and 15 of each 28-day cycle; treatment with maximum tolerated dose (MTD) | Drug | Phase 2a |
Primary outcome
Maximum Tolerated Dose (MTD) of BAL101553
Time frame: 28 day cycle
First 28-day treatment cycle dose limiting toxicities (DLT) graded according to 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
6 secondary outcomes
Safety and Tolerability of BAL101553 Treatment Based on Number of Patients With Related Treatment-emergent Adverse Events (TEAEs) in the Phase 1 and Phase 2a Safety Population at Various Dose Levels and Indication
Time frame: TEAEs with onset on or after Day 1 of the study and until 28 days after the last dose
AUC of BAL101553 and BAL27862
Time frame: 0 to 168 hours post-dose at Day 1 of Cycle 1 and Cycle 2 in each cohort in Phase 1, 28-day cycles
Cmax of BAL101553 and BAL27862
Time frame: Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.
Tmax of BAL101553 and BAL27862
Time frame: Pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 52, 54, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 1 and pre-dose, and 0.5, 1, 2, 4, 8, 24, 30, 48, 72 h, and 168 h after the start of study-drug infusion on Day 1 of Cycle 2.
Bioavailability of Daily Oral BAL101553 Measured by BAL27862 in Phase 1
Time frame: Relative oral bioavailability, calculated as dose-normalized AUC0-τ following oral administration on Cycle 2 Day 21 divided by dose normalized AUC0-∞ following IV administration on Cycle 1 Day 1 for each cohort.
Anti-tumor Activity of BAL101553 by Best Response Rate Per RECIST / RANO Criteria
Time frame: 28 day cycles
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36792805Joerger 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.
- Derived from this study: PubMed 31471863Joerger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Kaindl, MD study director
Basilea Pharmaceutica
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BAL101553 and BAL101553 at MTD in people with Neoplasms, run by Basilea Pharmaceutica at 6 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. 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 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Switzerland. 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 11 Oct 2021). 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?
Maximum Tolerated Dose (MTD) of BAL101553 (time frame: 28 day cycle). 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 NCT02895360, which also lists 2 linked publications.
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 10 May 2023.