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

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ClinicalTrials.gov Identifier: NCT02490800
Recruitment Status : Recruiting
First Posted : July 7, 2015
Last Update Posted : December 17, 2020
Sponsor:
Information provided by (Responsible Party):
Basilea Pharmaceutica

Tracking Information
First Submitted Date  ICMJE June 25, 2015
First Posted Date  ICMJE July 7, 2015
Last Update Posted Date December 17, 2020
Actual Study Start Date  ICMJE June 2015
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2020)
  • 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 ]
  • Phase 2a: Best objective response according to RANO criteria [ Time Frame: 28 day cycles ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2015)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2020)
  • 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
  • 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
  • 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
  • Cmax of BAL101553 and BAL27862 [ Time Frame: 28 day cycles ]
    Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of BAL101553 and BAL27862
  • Tmax of BAL101553 and BAL27862 [ Time Frame: 28 day cycles ]
    Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of BAL101553 and BAL27862
  • 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
  • Half-life of BAL101553 and BAL27862 [ Time Frame: 28 day cycles ]
    Pharmacokinetic parameter Half-life of BAL101553 and BAL27862
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2015)
  • 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
  • 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
  • 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
  • BAL101553 and BAL27862 pharmacokinetics (PK), including the effect of fasted versus fed states [ Time Frame: 11 day cycles ]
    Pharmacokinetic parameter "Peak Plasma Concentration" Cmax of BAL101553 and BAL28762
  • BAL101553 and BAL27862 pharmacokinetics (PK), including the effect of fasted versus fed states [ Time Frame: 11 day cycles ]
    Pharmacokinetic parameter "Time to Peak Plasma Concentration" Tmax of BAL101553 and BAL28762
  • BAL101553 and BAL27862 pharmacokinetics (PK), including the effect of fasted versus fed states [ Time Frame: 11 day cycles ]
    Pharmacokinetic parameter "Area under the plasma concentration versus time curve" AUC of BAL101553 and BAL28762
  • BAL101553 and BAL27862 pharmacokinetics (PK), including the effect of fasted versus fed states [ Time Frame: 11 day cycles ]
    Pharmacokinetic parameter Half-life of BAL101553 and BAL28762
  • Anti-tumor activity of daily oral BAL101553 in cancer patients based on RECIST 1.1 -criteria [ Time Frame: 28 day cycles ]
  • Exploratory assessment of baseline levels and change from baseline of circulating tumor cells and other biomarkers to characterize pharmacodynamic effects of daily oral BAL101553 [ Time Frame: 28 day cycles ]
  • Exploratory assessment of baseline levels and change from baseline of circulating tumor cells and other biomarkers in blood and/or tumor tissue for potential utility as predictive biomarkers. [ Time Frame: 28 day cycles ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE Drug: Oral daily administration of BAL101553
oral administration
Study Arms  ICMJE Experimental: Drug: BAL101553
Oral daily administration of BAL101553
Intervention: Drug: Oral daily administration of BAL101553
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 16, 2020)
87
Original Estimated Enrollment  ICMJE
 (submitted: July 2, 2015)
62
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Change 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Thomas Kaindl, MD +41 61 567 15 24 thomas.kaindl@basilea.com
Contact: Stephanie Anderson +41 61 567 15 24 stephanie.anderson@basilea.com
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02490800
Other Study ID Numbers  ICMJE CDI-CS-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Basilea Pharmaceutica
Study Sponsor  ICMJE Basilea Pharmaceutica
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Thomas Kaindl, MD Basilea Pharmaceutica International Ltd
PRS Account Basilea Pharmaceutica
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP