Clinical Trials /

Phase I Dose Escalation Study With an Allosteric AKT 1/2 Inhibitor in Patients

NCT01915576

Description:

This is the first study where BAY1125976 is given to humans. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1125976. The relative bioavailability of liquid service formulation and tablets will be determined. After the MTD is defined breast cancer patients with and without AKT1 mutation will be treated. The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1125976. BAY1125976 will be given daily as single oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Dose Escalation Study With an Allosteric AKT 1/2 Inhibitor in Patients
  • Official Title: A Phase I, Multi-center, Non-randomized, Open-label, Dose Escalation Design Study to Characterize Safety, Tolerability, Pharmacokinetics and Maximum Tolerated Dose of BAY 1125976 in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 16447
  • SECONDARY ID: 2012-004671-39
  • NCT ID: NCT01915576

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
BAY1125976BAY1125976 [once daily, dose-esc.]
BAY1125976BAY1125976 [twice daily, dose-esc.]
BAY1125976BAY1125976 [MTD]

Purpose

This is the first study where BAY1125976 is given to humans. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1125976. The relative bioavailability of liquid service formulation and tablets will be determined. After the MTD is defined breast cancer patients with and without AKT1 mutation will be treated. The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1125976. BAY1125976 will be given daily as single oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.

Trial Arms

NameTypeDescriptionInterventions
BAY1125976 [once daily, dose-esc.]ExperimentalOral administration once daily. Starting dose is 10 mg and will be escalated depending on any dose-limiting toxicities
  • BAY1125976
BAY1125976 [twice daily, dose-esc.]ExperimentalOral administration twice daily. Starting dose is 40mg twice daily and will be escalated depending on any dose-limiting toxicities
  • BAY1125976
BAY1125976 [MTD]ExperimentalOral administration of the defined MTD which shows optimal safety, PK profile, PD target inhibition and preliminary efficacy (once daily or twice daily) in different patient groups
  • BAY1125976

Eligibility Criteria

        Inclusion Criteria:

          -  For dose escalation cohorts: Subjects with advanced, histologically or cytologically
             confirmed solid tumors are eligible. Subjects' tumors (all comers) must be refractory
             to standard treatment with no standard therapy available, or subjects actively refuse
             any treatment, which would be regarded standard. In addition, the investigator must
             judge the experimental treatment as clinically and ethically acceptable

          -  For expansion cohort only: Subjects with histologically or cytologically proven
             metastatic breast cancer (with and without AKT1 E17K (G49A) mutation) or subjects with
             known AKT1 E17K (G49A) mutation in any other advanced solid tumor with at least one
             line of chemotherapy in the metastatic setting and not amenable to surgery with
             curative intent

          -  Subjects must have measurable disease (Response evaluation criteria in solid tumors
             (RECIST 1.1)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2

          -  Bone marrow, liver and renal functions as assessed by adequate laboratory methods to
             be conducted within 7 days prior to starting study treatment

          -  Subjects must provide tumor biopsies before treatment

          -  Recovery to CTCAE (Common Terminology Criteria for Adverse Events Version 4.03) Grade
             0 or Grade 1 or recovery to baseline preceding the prior treatment of any previous
             drug / procedure-related toxicity (except alopecia, anemia, and hypothyroidism)

        Exclusion Criteria:

          -  History of cardiac disease including congestive heart failure > New York Heart
             Association (NYHA) Class II

          -  Subjects with type 1 or type 2 diabetes mellitus

          -  Subjects with fasting glucose >125 mg/dL in 2 independent measurements or glycated
             hemoglobin (HbA1c) ≥ 7%

          -  Moderate and severe hepatic impairment, i.e. Child-Pugh B or C

          -  Active infections of CTCAE (Common Terminology Criteria for Adverse Events Version
             4.03) Grade >2 or infections of CTCAE Grade 2 not responding to therapy

          -  Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months from
             definitive therapy, has a negative imaging study within 4 weeks of study entry and is
             clinically stable with respect to the tumor at the time of study entry.

          -  Subjects undergoing renal dialysis

          -  Previous or concurrent cancer that is distinct in primary site or histology from the
             cancer being evaluated in this study except cervical carcinoma in situ, treated basal
             cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively
             treated > 3 years prior to study entry

          -  Autologous bone marrow transplant or stem cell rescue within 4 months of study entry

          -  Treatment with oral steroids (dose ≥ 10 mg/day of methylprednisolone or equivalent)

          -  Clinically relevant findings in the ECG such as a second- or third-degree AV block,
             prolongation of the QRS complex over 120 msec or of the QTcF-interval over 450 msec

          -  Acute toxic effects of previous anticancer chemotherapy or immunotherapy have to be
             normalized to CTCAE Grade equal or lower than 1 (excluding alopecia)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events as a measure of safety and tolerability
Time Frame:up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Food effect assessment
Time Frame:up to 2 years
Safety Issue:
Description:The effect of a high-fat, high-calorie meal on the pharmacokinetic parameters of BAY1125976 will be determined in 6 - 9 subjects in the MTD dose level or a lower dose level receiving the tablet for the cohort of the dose escalation part.
Measure:Tumor response will be evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) definitions
Time Frame:up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Bayer

Last Updated

December 26, 2016