Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 1 of 1 for:    NCT01915576
Previous Study | Return to List | Next Study

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Bayer
Information provided by (Responsible Party):
Bayer Identifier:
First received: July 29, 2013
Last updated: November 12, 2014
Last verified: November 2014

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.

Condition Intervention Phase
Drug: BAY1125976
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Bayer:

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

Secondary Outcome Measures:
  • Food effect assessment [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Tumor response will be evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) definitions [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAY1125976 [dose-esc.]
Oral administration once daily. Starting dose is 10 mg and will be escalated depending on any dose-limiting toxicities
Drug: BAY1125976
Oral administration once daily. Starting dose is 10 mg and will be escalated depending on any dose-limiting toxicities
Experimental: BAY1125976 [MTD]
Oral administration of MTD once daily in different patient groups
Drug: BAY1125976
Oral administration of MTD once daily in different patient groups


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01915576

Contact: Bayer Clinical Trials Contact
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

United States, California
Not yet recruiting
Santa Monica, California, United States, 90404
United States, Massachusetts
Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Texas
Not yet recruiting
Houston, Texas, United States, 77030
Villejuif Cedex, France, 94805
Heidelberg, Baden-Württemberg, Germany, 69120
St. Gallen, Sankt Gallen, Switzerland, 9007
Sponsors and Collaborators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer Identifier: NCT01915576     History of Changes
Other Study ID Numbers: 16447, 2012-004671-39
Study First Received: July 29, 2013
Last Updated: November 12, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Federal Office of Public Health
United States: Food and Drug Administration

Keywords provided by Bayer:
Phase I
Dose escalation
Breast cancer processed this record on November 19, 2014