Study With Wee-1 Inhibitor AZD1775 (MK-1775) and Carboplatin to Treat p53 Mutated Refractory and Resistant Ovarian Cancer

Inclusion Criteria:

* Histological or cytological proof of epithelial ovarian cancer, and proven p53 mutated pathway by PCR/Sequencing. IHC will also be performed. In the additional safety and efficacy cohort also inclusion of NSCLC, SCLC, cervical and endometrial cancer (only ovarian cancer cohort is pursued)
* 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 (relapse within 6 months in the additional safety and efficacy cohort)
* 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 in initial trial. In the additional safety and efficacy cohort: more than 2 prior cytotoxic chemotherapy regimens.
* 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.