Clinical trial NCT01164995 (phase 2, status: unknown status)
Conditions: epithelial ovarian cancer
ICD codes: H18.523, H18.521, H18.522, H18.529
Drugs: mk-1775 and carboplatin
SMILES: CN1CCN(CC1)C1=CC=C(NC2=NC=C3C(=O)N(CC=C)N(C3=N2)C2=NC(=CC=C2)C(C)(C)O)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological proof of epithelial ovarian cancer, and proven p53 mutated
             pathway by PCR/Sequencing. IHC will also be performed.

          -  Measurable disease on a CT-scan or elevated Cancer Antigen (CA)-125 levels that can be
             monitored.

          -  Patients previously received standard 1st line platinum therapy (combined with
             paclitaxel) for epithelial ovarian cancer, and showed recurrence on or within 3 months
             of this treatment.

          -  Able and willing to voluntarily give written informed consent.

          -  Able and willing to undergo blood sampling for pharmacokinetics and pharmacodynamics.

          -  Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and
             anti-tumor activity.

          -  Minimal acceptable safety laboratory values:

               -  Absolute neutrophil count (ANC) of ≥ 1.5 x 109 /L (or 1500/m3).

               -  Platelet count of ≥ 100 x 109 /L (or 100,000/mm3).

               -  Hemoglobin ≥ 5.6 mmol/L (or 9.1 g/dl).

               -  Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALAT and ASAT ≤ 2.5 x
                  ULN, or ALAT and ASAT ≥ 5x ULN in case of liver metastases.

               -  Renal function as defined by serum creatinine ≥ 1.5 x ULN or creatinine clearance
                  ≥ 60 ml/min for patients with creatinine levels ≥ 1.5 x ULN (by Cockcroft-Gault
                  formula).

          -  WHO performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  No radio- or chemotherapy within the last 4 weeks prior to study entry (palliative
             limited radiation for pain reduction is allowed)

          -  Able and willing to swallow oral medication.

          -  Able and willing to receive iv medication.

          -  Negative pregnancy test (urine/serum) for female patients with childbearing potential.

        Exclusion Criteria:

          -  Symptomatic cerebral or leptomeningeal metastases.

          -  Current participation or previous participation in a study with an investigational
             compound, or chemo- and/or radiotherapy within 28 days of receiving first dose of
             study medication. (Palliative limited radiation for pain reduction is allowed only
             between day 8 and day 21 of the study, and allowed to a limited area to palliate pain.

          -  No prior radiation therapy to more than 30% of the bone marrow and patient must have
             recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy.

          -  More than 1 prior cytotoxic chemotherapy regimen.

          -  Prior stem cell or bone marrow transplant.

          -  Unresolved (> grade 1) toxicities of previous chemotherapy, excluding alopecia.

          -  Known hypersensitivity to the components of the combination study therapy or its
             analogs.

          -  Patient has had prescription or non-prescription drugs or other products known to be
             metabolized by CYP3A4, or to inhibit or induce CYP3A4 that cannot be discontinued
             prior to Day 1 of dosing and withheld throughout the study until 2 days after the last
             dose of study medication

          -  Bowel obstructions or motility disorders that may negatively affect oral drug
             absorption.

          -  Patients with known alcoholism, drug addiction and/or a history of psychotic disorders
             who are not suitable for adequate follow up.

          -  Women who are pregnant or breast feeding.

          -  Fertile women who do not agree to use a reliable contraceptive method throughout the
             study.

          -  Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2
             type patients.

          -  Patients with a known history of hepatitis B or C.

          -  Neurological disease that may render a patient at increased risk for peripheral or
             central neurotoxicity.

          -  Clinical history suggestive for Li Fraumeni syndrome.