Clinical Trials /

BAY 1000394 for MCL-1-, MYC-, and CCNE1-Amplified Tumors



This research study is studying whether a new experimental cancer study drug BAY 1000394 will be helpful in treating solid tumor cancer with an abnormality in one of the following genes: Mcl-1, Myc or CCNE.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:



Phase 2

Trial Eligibility


BAY 1000394 for MCL-1-, <span class="go-doc-concept go-doc-biomarker">MYC</span>-, and <span class="go-doc-concept go-doc-biomarker">CCNE1</span>-<span class="go-doc-concept go-doc-keyword">Amplified</span> Tumors


  • Brief Title: BAY 1000394 for MCL-1-, MYC-, and CCNE1-Amplified Tumors
  • Official Title: A Phase II Study of BAY 1000394 in MCL1-Amplified, MYC-Amplified, CCNE1-Amplified Tumors
  • Clinical Trial IDs

    NCT ID: NCT02656849

    ORG ID: 15-380

    Trial Conditions

    Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    BAY 1000394 Roniciclib BAY 1000394

    Trial Purpose

    This research study is studying whether a new experimental cancer study drug BAY 1000394
    will be helpful in treating solid tumor cancer with an abnormality in one of the following
    genes: Mcl-1, Myc or CCNE.

    Detailed Description

    - This research study is a Phase II clinical trial. Phase II clinical trials test the
    effectiveness of an investigational drug to learn whether the drug works in treating a
    specific cancer.

    - "Investigational" means that the drug is still being studied and that research doctors
    are trying to find out more about it-such as the safest dose to use, the side effects
    it may cause, and if the drug is effective for treating different types of cancer.

    - It also means that the FDA (the U.S. Food and Drug Administration) has not approved BAY
    1000394 for use in participants with your type of cancer.

    - The study drug is a pan-CDK inhibitor targeting the genetic defect in several tumors,
    MCL1, Myc, or CCNE.

    Trial Arms

    Name Type Description Interventions
    BAY 1000394 Experimental After the screening procedures confirm eligibility to participate in the research study: Each treatment cycle lasts 4 weeks. Participants will take the study drug orally at predetermined times and dosage per cycle. BAY 1000394

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have advanced cancer for which no curative therapy exists and have a
    malignancy which matches one of the following cohorts:

    - MCL1 amplification ( 3 fold);

    - MYC amplification ( 6 fold);

    - CCNE1 amplification ( 6 fold).

    - Molecular abnormalities may be detected by any CLIA-certified test, including
    Massive Parallel (Next-Generation) sequencing platforms.

    - Patients must have measurable disease as defined by RECIST 1.1 criteria. In selected
    cases patients with evaluable disease may be eligible after discussion between the PI
    and Bayer.

    - Participants must have completed at least one line of therapy in the
    advanced/metastatic setting prior to enrollment

    - Participants with advanced disease for which approved second-line options exist will
    be eligible when they have progressed beyond such approved second-line therapy

    - Age 18 years. Because there is no data for evaluating these compounds in pediatric
    populations, the appropriate clinical trial can be conducted in the future in this
    specific population.

    - ECOG performance status of 0-1 (Karnofsky 70%, see Appendix A)

    - Life expectancy of greater than 12 weeks

    - Adequate bone marrow, liver, and renal functions as assessed by the following
    laboratory requirements:

    - Hemoglobin 8.5 g/dL

    - Absolute neutrophil count (ANC) 2 x 10/9/L

    - Platelet count 100 x 10/9/L

    - Total bilirubin 1.5 times the upper limit of normal (ULN)

    - Alanine aminotransferase (ALT) and aspartate transaminase (AST) 2.5 x ULN (5 x
    ULN for subjects with liver involvement of their cancer)

    - Prothrombin time-international normalized ratio (PT-INR) and partial
    thromboplastin time (aPTT) 1.5 x ULN

    - Estimated glomerular filtration rate (eGFR) 60 mL/min per 1.73 m/2 according to
    the Cockcroft-Gault formula

    - Negative serum pregnancy test in women of childbearing potential (WOCBP)(performed
    within 7 days of randomization). Negative results must be available prior to study
    treatment administration

    - Women of childbearing potential and men must agree to use adequate barrier birth
    control measures from the time of signing of the informed consent form until at least
    3 months after the last study drug administration. The investigator or a designated
    associate is requested to advise the subject on how to achieve adequate birth
    control. Adequate contraception is defined in the study as any medically recommended
    method (or combination of methods) as per standard of care. These procedures should
    be documented in source documents. Postmenopausal women are defined as:

    - Age >50 years with amenorrhea for at least 12 months or

    - Age 50 years with 6 months of spontaneous amenorrhea and follicle stimulating
    hormone level within postmenopausal range (>40 mIU/mL) or

    - Bilateral oophorectomy

    - Additional adequate contraception which includes hormonal contraception with
    implants or combined oral contraceptives, certain intrauterine devices,
    bilateral tubal ligation, hysterectomy, or vasectomy of the partner is allowed
    as long as a barrier method is also being used

    - Ability to understand and the willingness to sign a written informed consent

    Exclusion Criteria:

    - Prior radiotherapy is permitted but must have occurred 2 weeks (palliative
    radiotherapy) or 4 weeks (curative radiotherapy) and subject must have no Grade 3
    or 4 toxicities prior to first dose of study treatment

    - Prior chemotherapy is allowed. Patients must not have received chemotherapy for 3
    weeks prior to the initiation of study treatment and must have full recovery from any
    acute effects of any prior chemotherapy. Patients must not have had nitrosoureas or
    mitomycin C for 6 weeks prior to the initiation of study treatment.

    - Prior exposure to approved receptor tyrosine kinase inhibitors is permitted. At least
    5 half-lives must have elapsed since the completion of the kinase inhibitor and the
    initiation of study treatment.

    - Prior experimental (non-FDA approved) therapies and immunotherapies are allowed.
    Patients must not have received these therapies for 4 weeks prior to the initiation
    of study treatment and must have full recovery from any acute effects of these

    - Participants must not have received pan-cyclin-dependent kinase inhibitors as prior

    - Current or ongoing administration of anticoagulation or antiplatelet therapy.
    However, use of low-dose aspirin (100 mg/day) and/or low-dose heparin is permitted
    unless it is being used for conditions other than cancer

    - Known hypersensitivity to any of the study treatments or excipients of the
    preparations or any agent given in association with this study

    - Previous deep vein thrombosis (within the last 6 months), arterial thrombotic events
    (including strokes), or pulmonary embolism

    - History of cardiac disease: Congestive heart failure New York Heart Association
    (NYHA) Class III or IV angina (within past 6 months prior to study entry), myocardial
    infarction, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers
    or digoxin are permitted)

    - Known human immunodeficiency virus infection, active hepatitis B or C, or chronic
    hepatitis B or C requiring treatment with antiviral therapy

    - Active clinically serious infections of NCI-CTCAE v4.0 >Grade 2

    - Seizure disorder requiring therapy (such as steroids or anti-epileptics)

    - Concomitant use of other medications that are known to lower the seizure threshold

    - Symptomatic metastatic brain or meningeal tumors, including those of the spinal cord,
    and including cases of neoplastic meningitis (also known as carcinomatous meningitis
    or leptomeningeal carcinomatosis).

    - History of organ allograft

    - Evidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of
    NCI-CTCAE v4.0 >Grade 2 within 4 weeks prior to the first dose of study treatment

    - Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood
    pressure >90 mmHg despite optimal medical management)

    - Serious, non-healing wound, ulcer, or bone fracture (bone fractures due to bone
    metastases are acceptable)

    - Subjects on dialysis

    - Sensory neuropathy with sensory alterations or paresthesia (including tingling),
    interfering with function (NCI-CTCAE v4.0 Grade 2)

    - Previous or coexisting cancer that is distinct from the study indication and has not
    been curatively treated >3 years prior to study entry EXCEPT cervical cancer in-situ,
    treated basal cell carcinoma, superficial bladder tumors (Ta and Tis)

    - Any condition that is unstable or could jeopardize the safety of the subject and
    his/her compliance in the study

    - Subjects unable to swallow oral medications

    - Any malabsorption condition

    - Major surgery, open biopsy, or significant trauma within 4 weeks prior to the first
    dose of study treatment is excluded (central line surgery is not considered major

    - Autologous bone marrow transplant or stem cell rescue within 4 months prior to first
    dose of study treatment is not allowed

    - Investigational drug treatment outside of this study during or within 4 weeks prior
    to study entry. Toxic effects of previous investigational drug treatment have to be

    - Potent CYP3A4 inhibitors and CYP3A inducers (see Appendix B)

    - Pregnant or breast-feeding women

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Six-month progression-free survival rate

    Secondary Outcome Measures

    Response Rate Mcl1-amplified tumors

    Response Rate MYC-amplified tumors

    Response Rate CCNE1-amplified tumors

    Overall Survival

    Time to Progression

    Trial Keywords

    Solid Tumor