check_circleStudy Completed

Neoplasms

Bayer Identifier:

16447

ClinicalTrials.gov Identifier:

NCT01915576

EudraCT Number:

2012-004671-39

EU CT Number:

Not Available
Phase I dose escalation study with an allosteric AKT 1/2 inhibitor in patients

Trial 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.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - 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)
  • - 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)

Trial summary

Enrollment Goal
79
Trial Dates
September 2013 - December 2016
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY1125976
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Heidelberg, 69120, Germany
Completed
St. Gallen, 9007, Switzerland
Completed
Houston, 77030, United States
Completed
Santa Monica, 90404, United States
Completed
VILLEJUIF CEDEX, 94805, France
Completed
St. Louis, 63110, United States
Completed
Boston, 02215, United States

Primary Outcome

  • Number of participants with adverse events as a measure of safety and tolerability
    date_rangeTime Frame:
    up to 2 years
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    Safety Issue:
    Yes
  • Maximum tolerated dose (MTD) of BAY1125976
    date_rangeTime Frame:
    up to 2 years
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    Safety Issue:
    Yes
  • Area under the plasma concentration vs time curve from zero to infinity after single (first) dose
    date_rangeTime Frame:
    at pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose
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    Safety Issue:
    No

Secondary Outcome

  • Food effect assessment
    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.
    date_rangeTime Frame:
    up to 2 years
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    Safety Issue:
    No
  • Tumor response will be evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) definitions
    date_rangeTime Frame:
    up to 2 years
    enhanced_encryption
    Safety Issue:
    No

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
3

Additional Information

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