| Eligibility |
INCLUSION CRITERIA:
1. Histologically or cytologically documented, incurable, unresectable locally advanced,
or metastatic breast cancer
2. Histologically documented metastatic or locally advanced unresectable breast cancer
that is ER and progesterone receptor (PR) <10% expression and does not over-express
Hormone Estrogen Receptor-Positive (HER2) protein (Immunohistochemistry (IHC) 0, 1+,
or 2+ and Fluorescent in situ hybridization (FISH) <2.0)
3. Patient must consent to a biopsy of a site of disease unless the only site of disease
is lung/pleura, bone, or deemed unsafe by the principal investigator
4. Patient is male or female and =18 years of age on the day of signing informed consent.
5. Patient must have performance status of 0-1 on the Eastern Cooperative Oncology Group
(ECOG) Performance Scale and life expectancy > 3 months
6. Patient must have evaluable disease
7. Patient must have adequate organ function as indicated by the following laboratory
values:
Hematological
- Absolute neutrophil count (ANC) = 1,500 /µL
- Platelets = 100,000 /µL
- Hemoglobin = 9 g/dL
Renal
- Serum creatinine or calculated creatinine clearance = 1.5 x upper limit of normal
(ULN) OR
- = 60 mL/min for patients with creatinine levels > 1.5 x institutional ULN
Hepatic
- Serum total bilirubin = 1.5 x ULN OR direct bilirubin = ULN for patients with
total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT)
and alanine aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SGPT) =
2.5 x ULN, = 5 x ULN if liver metastasis
Coagulation
- Prothrombin time (PT)/International Normalized Ratio (INR) = 1.2 x ULN
- Partial thromboplastin time (PTT) = 1.2 x ULN
8. Female patient of childbearing potential must have a negative serum or urine pregnancy
test ß-human chorionic gonadotropin (hCG) within 72 hours prior to first doses of
study medication . If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
9. Female subjects of childbearing potential must be willing to use an adequate method of
contraception for the course of the study through 120 days after the last dose of
study medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. Male subjects of childbearing potential must agree to use an adequate method of
contraception starting with the first dose of study therapy through 120 days after the
last dose of study therapy. Note: Abstinence is acceptable if this is the usual
lifestyle and preferred contraception for the subject.
11. Patient has voluntarily agreed to participate by giving written informed consent
12. Concomitant use of bisphosphonates or nuclear factor-?B (RANK) ligand inhibitors is
allowed.
EXCLUSION CRITERIA:
1. Patient who has had radiotherapy within 1 week (or unresolved radiation-related
toxicities), chemotherapy within 2 weeks or 5 half-lives, whichever is longer (6 weeks
for nitrosoureas, mitomycin C or bevacizumab), anti-cancer monoclonal antibody for
direct anti-neoplastic treatment within 3 weeks, or who has not recovered from
toxicity due to previous agents administered. If the patient has residual toxicity
from prior treatment, toxicity must be = Grade 1 (except for neuropathy and alopecia).
2. > 2 lines of prior chemotherapy in the metastatic setting
3. Serum lactate dehydrogenase (LDH) > 1.5x institutional ULN
4. Patients less than 2 weeks post major surgical procedure (all surgical wounds must be
fully healed). For the purpose of this criterion, a major surgical procedure is
defined as one requiring the administration of general anesthesia.
5. Patient is currently participating in a study with an investigational compound or
device.
6. Patient has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. However, patients with CNS metastases who have completed a course of
therapy would be eligible for the study provided they are clinically stable for at
least 4 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS
metastasis on brain imaging within 4 weeks of enrollment (2) off steroids for 2 weeks.
Patients with clinically insignificant brain metastases that do not require treatment
are eligible.
7. Patient has a primary central nervous system tumor
8. Patient has known hypersensitivity to the components of study drug or its analogs.
9. Patient has a history or current evidence of clinically significant heart disease
including:
- Clinically significant congestive heart failure, unstable angina pectoris,
- Clinically significant cardiac arrhythmia,
- Myocardial infarction during the last 6 months, and/or a current ECG tracing that
is abnormal in the opinion of the treating Investigator,
- QTc prolongation >480 msec (Bazett's Formula),
- Congenitally long QT syndrome, and/or current anti-arrhythmic therapy
10. Patient with evidence of clinically significant bradycardia (HR <50), or a history of
clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree
atrioventricular (AV) block (Mobitz Type 2), Patient with uncontrolled hypertension
(=140/90 mmHg). Patients who are controlled on antihypertensive medication will be
allowed to enter the study.
11. Patient has a history or current evidence of any condition, therapy, or lab
abnormality that might confound the results of the study, interfere with the patient's
participation for the full duration of the study, or is not in the best interest of
the patient to participate, in the opinion of the treating investigator.
12. Patient has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
13. Patient is, at the time of signing informed consent, a regular user of any illicit
drugs or had a recent history (within the last year) of drug or alcohol abuse.
14. Patient is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the study
15. Patient is known to be Human Immunodeficiency Virus (HIV)-positive
16. Patient has known history of active Hepatitis A, B, or C
17. Patients who have known allergic reactions to IV contrast dye despite standard
prophylaxis
18. Patients who require medications that are strong CYP3A4 inhibitors or inducers.
19. Patients who have discontinued any of these medications must have a wash-out period of
at least 5 days or at least 5 half-lives of the drug (whichever is longer) prior to
the first dose of dinaciclib (Refer to Appendix 2 Drugs that interact strongly with
CYP3A4).
20. Patients requiring warfarin therapy are excluded, low molecular weight heparin is
permitted.
21. Patient has a diagnosis of immunodeficiency or is receiving ongoing immunosuppressive
therapy, including systemic or enteric corticosteroids except for non-systemically
absorbed treatments (such as inhaled or topical steroid therapy for asthma, chronic
obstructive pulmonary disease, allergic rhinitis). Patient must be off systemic
steroid or any other form of immunosuppressive therapy within 7 days prior to first
dose of trial treatment.
22. Patient is diagnosed with active autoimmune disease that has required systemic
treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids
or immunosuppressive drugs). Note: replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
is not considered a form of systemic treatment.
23. Patient has history of interstitial lung disease or known history of, or any evidence
of active, noninfectious pneumonitis.
24. Patient has history of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or prior allogeneic bone marrow
transplantation or prior solid organ transplantation.
25. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
Inclusion of women and minorities:
Both men and women and members of all races and ethnic groups are eligible for this trial.
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