Clinical trial NCT01085422 (phase 1, status: completed)
Conditions: prostate cancer
ICD codes: C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: abt-888, temozolomide
SMILES: C[C@@]1(CCCN1)C1=NC2=CC=CC(C(N)=O)=C2N1, CSCC[C@H](N)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Subject has histologically or cytologically confirmed prostate cancer.

          -  Metastatic prostate cancer with measurable and/or bony disease that has progressed
             despite androgen deprivation therapy and at least one and no more than two prior
             systemic non hormonal therapies (at least one must include docetaxel) for castration
             resistant metastatic disease.

          -  At least 28 days must have elapsed since completion of prior anti-cancer therapy and
             must have recovered from all side effects to < Grade 1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. ECOG PS 3 is
             allowed if due to pain.

          -  Subjects must have PSA progression defined as:

               -  A 25% increase in PSA over a baseline value with an increase in the absolute
                  value of PSA level by 2 ng/ml, that is confirmed by another PSA level at a
                  minimum of 1 week interval.

          -  Subjects must have a minimum PSA of > 2 ng/ml.

          -  Testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with a
             luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone
             orchiectomy.

          -  No investigational or commercial agents (other than LHRH analogue) or therapies
             including other hormonal agents such as antiandrogens or herbal medications may be
             administered with the intent to treat the subject's malignancy. Subjects on stable
             doses of steroids or megestrol acetate (for hot flashes or appetite) are allowed.

          -  Four weeks must have elapsed since major surgery.

          -  Prior radiotherapy is allowed as long as the bone marrow function is adequate and at
             least 4 weeks has elapsed since completion of radiation therapy. No prior
             radiopharmaceuticals are allowed.

          -  Subjects must have normal organ and bone marrow function as defined below obtained
             within two weeks from treatment initiation:

               -  Bone Marrow: absolute neutrophil count ≥ 1,500/mcL; platelets ≥ 100,000/mcL;
                  hemoglobin ≥ 9.0 g/dL

               -  Renal function: Serum creatinine ≤ 1.5 × upper limits of institution's normal
                  (ULIN) range or creatinine clearance ≥ 50 mL/min/1.73 m2

               -  Hepatic Function: Aspartate aminotransferase (AST) and/or alanine transaminase
                  (ALT) ≤ 2.5 × ULIN. For subjects with liver metastases, AST and/or ALT < 5 ×
                  ULIN. Bilirubin ≤ 1.5 × ULIN (Subjects with Gilbert's Syndrome may have a
                  bilirubin ≥ 1.5 × ULIN)

          -  Subjects who refuse to provide blood samples for the correlative studies will be
             eligible.

          -  ABT-888 and temozolomide are known to be teratogenic, therefore men must agree to use
             adequate contraception (hormonal or barrier method of birth control; abstinence) prior
             to study entry and for the duration of study participation.

          -  Subjects with treated and controlled epidural disease are permitted into the study.

          -  Subject is capable of understanding and complying with parameters as outlined in the
             protocol and able to sign and date the informed consent, approved by an Independent
             Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of
             any screening or study specific procedures.

        Exclusion Criteria:

          -  A subject with cord compression or a history of uncontrolled central nervous system
             (CNS) metastases or leptomeningeal disease.

          -  Subject has had prior therapies with Dacarbazine (DTIC) or TMZ containing regimens.

          -  The subject has received an investigational agent within 28 days prior to study drug
             administration.

          -  Subject with a history of seizure disorder and currently receiving medications for
             seizure disorders (e.g., steroid or anticonvulsant drugs).

          -  The subject has had another active malignancy within the past 1 year with the
             exception of definitely treated carcinomas in situ, superficial bladder cancer, and
             non-melanoma carcinoma of the skin. Questions regarding inclusion of individual
             subjects should be discussed with the Abbott Medical Monitor.

          -  Clinically significant and uncontrolled major medical condition(s) including but not
             limited to:

               -  active uncontrolled infection,

               -  symptomatic congestive heart failure,

               -  unstable angina pectoris or cardiac arrhythmia,

               -  Psychiatric illness/social situation that would limit compliance with study
                  requirements,

               -  Or any medical condition, which in the opinion of the study investigator places
                  the subject at an unacceptably high risk for toxicities.

          -  Subject has previously been treated with a PARP inhibitor.