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Trial record 1 of 1 for:    NCT01915576
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Phase I Dose Escalation Study With an Allosteric AKT 1/2 Inhibitor in Patients

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01915576
First Posted: August 5, 2013
Last Update Posted: December 28, 2016
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.
Information provided by (Responsible Party):
Bayer
  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.


Condition Intervention Phase
Neoplasms Drug: BAY1125976 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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

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 ]
  • Maximum tolerated dose (MTD) of BAY1125976 [ Time Frame: up to 2 years ]
  • 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 ]

Secondary Outcome Measures:
  • Food effect assessment [ Time Frame: up to 2 years ]
    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 ]

Enrollment: 79
Study Start Date: September 2013
Study Completion Date: December 2016
Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAY1125976 [once daily, 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 [twice daily, dose-esc.]
Oral administration twice daily. Starting dose is 40mg twice daily and will be escalated depending on any dose-limiting toxicities
Drug: BAY1125976
Oral administration twice daily. Starting dose is 40mg twice daily and will be escalated depending on any dose-limiting toxicities
Experimental: BAY1125976 [MTD]
Oral 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
Drug: BAY1125976
Oral 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

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
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): NCT01915576


Locations
United States, California
Santa Monica, California, United States, 90404
United States, Massachusetts
Boston, Massachusetts, United States, 02215
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Texas
Houston, Texas, United States, 77030
France
Villejuif Cedex, France, 94805
Germany
Heidelberg, Baden-Württemberg, Germany, 69120
Switzerland
St. Gallen, Sankt Gallen, Switzerland, 9007
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01915576     History of Changes
Other Study ID Numbers: 16447
2012-004671-39 ( EudraCT Number )
First Submitted: July 29, 2013
First Posted: August 5, 2013
Last Update Posted: December 28, 2016
Last Verified: December 2016