An Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP-1 and PARP-2 Inhibitor) as Single-Agent Therapy and as Combination Therapy With Temozolomide in Patients With Advanced Solid Tumors
- The patient has a histologically or cytologically confirmed malignant advanced solid
tumor considered unresponsive or poorly responsive to accepted treatment modalities.
- The patient has adequate hematologic assessments and adequate renal and hepatic
functions as specified in the study protocol.
- The patient has measurable or nonmeasurable disease documented with an appropriate
method of evaluation according to disease characteristics.
- The patient has had no chemotherapy for at least 3 weeks and has resolution of prior
sequelae. If the patient has had prior curative radiation or prior treatment with
nitrosoureas, a minimum of 4 weeks and 6 weeks, respectively, must have elapsed
before treatment with CEP-9722.
- The patient has had no immunotherapy, including monoclonal antibody therapy, for at
least 4 weeks and no hormonotherapy for at least 1 week, with the exception of
patients with prostate cancer, who may continue hormonal therapy.
- 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.
- Agreement by women of childbearing potential (not surgically sterile or 2 years
postmenopausal) to use a medically accepted method of contraception and continue the
use of this method for the duration of the study and for 90 days after participation
in the study. Acceptable methods of contraception include abstinence, barrier method
with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral,
transdermal, implanted, and injected) in conjunction with a barrier method.
- Agreement by men not surgically sterile or who are capable of producing offspring to
practice abstinence or use a barrier method of birth control, and continue use of
this method for the duration of the study and for 6 months after participation in the
- The patient has a primary brain tumor whose disease requires a systematic
premedication with anticonvulsive agents.
- The patient has baseline cardiac abnormalities outside of the specified study
- The patient has clinically symptomatic recurrent/progressive brain metastases within
4 weeks (stable sequelae are acceptable).
- The patient has previous hypersensitivity reactions to 1 of the components of
CEP-9722, temozolomide, or dacarbazine.
- The patient is a pregnant or breast-feeding woman. (Any women becoming pregnant
during the study will be withdrawn from the study.)
- The patient is participating in another interventional clinical study at the time of
enrollment, has participated in another interventional clinical study within 4 weeks
prior to enrollment, or the patient has previously been already enrolled in this
- The patient has an active gastroduodenal ulcer, uncontrolled high blood pressure,
uncontrolled diabetes mellitus, or uncontrolled angina pectoris; has had a recent
myocardial infarction; has had a cerebrovascular event within 6 months prior to study
entry; or has pre-existing coagulopathy.
- The patient has a concomitant uncontrolled infection or severe systemic disease.
- The patient has a known nephropathy or hepatopathy.
- The patient is receiving concurrent treatment with an antineoplastic agent other than
- The patient has had previous treatment with another PARP inhibitor.
- The patient is unable to swallow capsules.
- The patient has taken any medications which are contraindicated as specified in the
- The patient has any serious or uncontrolled nonmalignant medical disorder or