An Open-Label Study to Determine the Maximum Tolerated Dose of the PARP Inhibitor CEP-9722 When Administered as a Single Agent in Patients With Advanced or Metastatic Solid Tumors
- The patient has histologically confirmed, locally advanced or metastatic solid tumor
considered incurable and unresponsive to standard therapies.
- The patient has disease progression following at least 1 prior standard chemotherapy
- The patient is a man or woman at least 18 years of age.
- The patient has a European Cooperative Oncology Group (ECOG) performance status of 0,
1, or 2.
- The patient has a life expectancy of 12 weeks or more.
- The patient has adequate hematologic function as evidenced by:
- absolute neutrophil cell (ANC) count 1.5 x109/L or more
- hemoglobin 10 g/dL or more
- platelets 100 x 109/L or more
- The patient has adequate hepatic function as evidenced by:
- total bilirubin 1.5 times the upper limit of normal (ULN) or less, unless
secondary to Gilbert's disease (any Gilbert's disease must be documented, and
bilirubin must be 3 times the ULN or less.)
- alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline
phosphatase of 2.5 times ULN or less
- The patient has adequate renal function as defined by creatinine of less than 1.5
times ULN or less.
- The patient must take precautions to not become pregnant or produce offspring. Women
must be of non-childbearing potential (surgically sterile or postmenopausal for at
least 12 months, confirmed by follicle-stimulating hormone [FSH] >40 IU/L) or agree
to use a medically accepted method of contraception for the duration of the study and
90 days after treatment. Men must be surgically sterile or agree to use a medically
accepted method of contraception for the duration of the study and 90 days after
treatment. Acceptable methods of contraception include abstinence, barrier method
with spermicide (excluding cervical cap and sponge), intrauterine device (IUD), or
steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction
with a barrier method.
- Written informed consent is obtained.
- In Part 2: In addition to the criteria above, patients should have documented
deficiencies of DNA repair pathways, such as BRCA1/2, or have prostate, breast, or
gastric cancer and ability to provide fresh or archived tumor specimens.
- Other than malignancy, the patient has any serious or uncontrolled surgical, medical,
or psychiatric history that could pose an unacceptable health risk to the patient,
prevent compliance with study procedures, or compromise the study integrity,
including, but not limited to the following:
1. recent history of cardiac ischemic disease (acute myocardial infarction within 6
months, unstable angina)
2. cardiac arrhythmia that is uncontrolled or that requires medication
3. recent transient ischemic attack or stroke (within 6 months) or residual
dysfunction from stroke
4. history of seizure disorder (part 1 only)
5. clinically significant pulmonary disease (eg, fibrosis on chest x-ray or
significant dyspnea as assessed by investigator)
6. poorly controlled hypertension (systolic >140 mm Hg or diastolic >90 mm Hg)
7. uncontrolled active infection within the past 7 days
8. poorly controlled diabetes mellitus as assessed by investigator
9. recent major surgery (within 4 weeks prior to study day 1) or minor surgery
(within 2 weeks prior to study day 1)
- The patient has previously received a PARP inhibitor.
- The patient has received antitumor therapy or other investigational agent within 4
weeks (with the exception of LHRH therapy in patients with prostate cancer) or
nitrosourea therapy within 6 weeks.
- The patient has clinically symptomatic brain metastases or required treatment for
brain metastases within 4 weeks (stable sequelae acceptable if treatment has been
- The patient has residual adverse events of greater than grade 1 severity from prior
radiotherapy or chemotherapy agents.
- The patient has known immunodeficiency virus (HIV) infection, acute or chronic
hepatitis B infection,or hepatitis C infection.
- The patient is a pregnant or breast-feeding woman. (Any women becoming pregnant
during the study will be withdrawn from the study.)
- The patient has medical or surgical gastrointestinal history that would interfere
with the absorption of study drug.
- The patient requires treatment with a proton pump inhibitor or H2 antagonist or has
taken a proton pump inhibitor or H2 antagonist within 4 days before CEP-9722
- The patient has risk factors for Torsades de Pointes as follows:
- history of Long QT syndrome or unexplained syncope
- history of congestive heart failure (New York Heart Association class III or IV)
- concomitant treatment with medication known to prolong QT/QTc interval
- QTc greater than 450 msec at screening