- 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.
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
document
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 therapies.
- Participants must not have received pan-cyclin-dependent kinase inhibitors as prior
therapy.
- 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
surgery)
- 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
normalized
- Potent CYP3A4 inhibitors and CYP3A inducers (see Appendix B)
- Pregnant or breast-feeding women
