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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02490800
Recruitment Status : Active, not recruiting
First Posted : July 7, 2015
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
Basilea Pharmaceutica

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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Oral daily administration of BAL101553 Phase 1 Phase 2

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.

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, additional patients will be treated at that dose (this part is called "dose expansion") to further assess the tolerability and potential anticancer activity of oral BAL101553. The study will also measure pharmacokinetics, pharmacodynamic effects and assess biomarkers.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 2015
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Drug: BAL101553
Oral daily administration of BAL101553
Drug: Oral daily administration of BAL101553
oral administration




Primary Outcome Measures :
  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 ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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 BAL27862

  5. 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 BAL27862

  6. 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 BAL27862

  7. 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 BAL27862

  8. 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 ]
  9. Anti-tumor activity of daily oral BAL101553 in cancer patients based on CA-125 Rustin criteria or PSA Working group 2 criteria (non-measurable disease of ovarian or prostate cancer). [ Time Frame: 28 day cycles ]
  10. 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 ]
  11. 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 ]
  12. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Patients who have 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.
  3. Patients with advanced solid tumors must have measurable disease or non-measurable prostate or ovarian cancer that can be followed by prostate specific antigen (PSA) or cancer antigen-125 (CA- 125).

    Patients with glioblastoma or high-grade glioma must have measurable disease, defined by contrast-enhancing MRI. Patients with previous lowgrade glioma that progressed after prior radiotherapy and are found to have high-grade glioma/GBM by biopsy or imaging.

  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 6 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.
  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) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02490800


Locations
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United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom, G12 0YN
University College London NHS Foundation Trust
London, United Kingdom, NW1 2BU
Sir Bobby Robson Cancer Trials Research Centre; Northern Centre for Cancer Care
Newcastle upon Tyne, United Kingdom, NE7 7DN
Royal Marsden Hospital
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Basilea Pharmaceutica
Investigators
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Study Director: Marc Engelhardt, MD Basilea Pharmaceutica International Ltd

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Responsible Party: Basilea Pharmaceutica
ClinicalTrials.gov Identifier: NCT02490800    
Other Study ID Numbers: CDI-CS-002/4.0
First Posted: July 7, 2015    Key Record Dates
Last Update Posted: May 18, 2020
Last Verified: August 2019
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue