stop_circleTerminated/Withdrawn

Medical Oncology

Bayer Identifier:

17450

ClinicalTrials.gov Identifier:

NCT02439346

EudraCT Number:

2014-004810-27

EU CT Number:

Not Available
Phase I dose escalation and expansion of oral BAY 1143269 in combination with intravenous docetaxel

Trial purpose

Determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and/or recommended Phase II dose (RP2D) of oral BAY 1143269 given alone or in combination with intravenous (IV) docetaxel in subjects with advanced solid tumors.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - Male or female subjects aged > 18 years
    - Subjects must have histologically or cytologically confirmed locally advanced or metastatic solid tumors and must be refractory to any standard therapy, or have no standard therapy available, or have actively refused any standard therapy or, in the investigator's opinion, experimental treatment in this study is clinically and ethically acceptable for the subject.
    - Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1)
    - Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    - Subjects must have a life expectancy of at least 12 weeks
    - Subjects must have adequate bone marrow function as assessed by the following: hemoglobin >=9.0 g/dL or >=5.6 mmol/L, absolute neutrophil count (ANC) >=1.500/mm^3 or >=1.5 x 10^9/L (CTCAE Grade <=1), platelet count >= 100000/mm^3 or >=100 x 10^9/L
    - Subjects must have adequate kidney function, as assessed by the estimated glomerular filtration rate (eGFR) >=60 mL/min per 1.73 m*2 [Common Terminology Criteria for Adverse Events(CTCAE Grade <=1)] calculated by the Modification of Diet in Renal Disease Study Group (MDRD) formula
    - Subjects must have adequate liver function assessed by: total bilirubin <= 1.0 x upper limit of normal (ULN), aspartate aminotransferase (ALT) <= 3.0 x ULN (CTCAE Grade <=1) or, if receiving BAY1143269 in combination with IV docetaxel, AST and ALT <=1.5 x ULN if concomitant with alkaline phosphatase increase >2.5 x ULN
    - Subjects must have adequate coagulation as assessed by: international normalized ratio (INR) or prothrombin time (PT) <=1.5 times ULN (CTCAE Grade <=1), partial thromboplastin time (PTT) <=1.5 x ULN (CTCAE Grade <=1)
    - Women of reproductive potential must have a negative serum beta human chorionic gonadotropin (b-HCG) pregnancy test within 7 days before the first dose of study drug. Women of reproductive potential and men with female partners of childbearing potential must agree to consistently use highly effective contraception between signing the informed consent and 60 days after the last administration of study drug

  • - Subjects who have a 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 and Tis) or any previous cancer curatively treated <3 years before the first dose of study drug
    - Subjects who have a history of, or current evidence of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE Grade >= 2 <4 weeks before the first dose of study drug.
    - Subjects who have new or progressive brain or meningeal or spinal metastases
    - Subjects who have a history of, or current evidence of uncontrolled cardiovascular disease or a left ventricular ejection fraction (LVEF) <50%
    - Women who are pregnant or breast-feeding
    - Subjects experiencing unresolved toxicity of previous antitumor therapy (excluding alopecia) which is CTCAE Grade >1 at screening
    - Subjects who are current smokers or users of other tobacco products or have quit <90 days before first dose of study drug
    - Subjects taking or likely to take strong and moderate CYP2D6 inhibitors, strong CYP1A1 inhibitors, and/or CYP1A1/CYP1A2 sensitive substrates or with narrow therapeutic index. Subjects receiving oral BAY1143269 and IV docetaxel must not take or be likely to take strong CYP3A1 inhibitors
    - Subjects who have received systemic antitumor therapy within 4 weeks or radiotherapy to target lesions within 3 weeks before the first dose of study drug, which is longer
    - Subjects who had received investigational drug treatment, including BAY1143269 and docetaxel, outside of this study within 4 weeks before the first dose of study drug, or for small molecules within the 5 half-lives of the agent before the first dose of study drug, whichever is longer

Trial summary

Enrollment Goal
15
Trial Dates
June 2015 - April 2017
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY1143269
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Withdrawn
Santa Monica, 90403, United States
Completed
San Antonio, 78229, United States
Completed
Dallas, 75246, United States
Completed
Sutton, SM2 5PT, United Kingdom
Completed
Houston, 77030, United States

Primary Outcome

  • Maximum Tolerated Dose (MTD) of Oral BAY1143269 Alone and in Combination With Intravenous Docetaxel
    The MTD of oral BAY1143269 given alone was defined as the maximum dose at which the predicted incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 30 percent (%).
    date_rangeTime Frame:
    Up to 2 years
    enhanced_encryption
    Safety Issue:
    Yes
  • Maximum Observed Drug Concentration (Cmax) in Plasma After Single and Multiple Dose Administration of BAY1143269
    Maximum observed concentration of BAY1143269 in plasma after single dose and multiple dose administration was measured.
    date_rangeTime Frame:
    Cycle 1, 2 Day 1: Pre-dose to 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    Yes
  • Area Under the Concentration-time Curve From Time Zero to 24 Hours [AUC(0-24)] After Single and Multiple Dose Administration of BAY1143269
    Area under the concentration-time curve from zero to 24 hours after single dose and multiple dose administration of BAY1143269 in plasma was measured.
    date_rangeTime Frame:
    Cycle 1, 2 Day 1: Pre-dose to 24 hours post-dose
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • Tumor response
    Tumor response was assessed by Response Evaluation Criteria in Solid Tumors(RECIST V1.1). Evaluation of target lesions included CR(Disappearance of all target lesions),PR(at least a 30% decrease in sum of diameters of target lesions),PD:at least a 20% increase in sum of diameters of target lesions, taking smallest sum recorded as reference since treatment started or appearance of one or more new lesions) and Stable disease(SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD).Evaluation of non-target lesions included CR(disappearance of all non-target lesions and normalization of tumor marker level),Non-CR/PD(Persistence of 1 or more non target lesions and/or maintenance of tumor marker level above normal limits) and PD(Appearance of 1 or more new lesions and/or unequivocal progression of existing non target lesions).
    date_rangeTime Frame:
    Baseline; end of Cycle 2
    enhanced_encryption
    Safety Issue:
    No

Trial design

An open-label, non-randomized, multicenter Phase I study to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and maximum tolerated dose of oral MKNK1 inhibitor BAY 1143269 given alone or in combination with intravenous docetaxel in subjects with advanced solid tumors
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
Open Label
Assignment
Sequential Assignment
Trial Arms
4

Additional Information

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