Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

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

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.
  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.

Eligibility: 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.

Relevance to patient case: not relevant