matastatic disease solid tumours
Conditions
Interventions
Dose escalation phase:
Part I:
Cycle 1 will be of 28 days* duration. KU-0059436 will be administered twice
daily for 28 days. Carboplatin will be administered on day 8. All subsequent
cycles will be
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Full informed consent 2. Dose escalation phase: male or female patients with a histologically or cytologically diagnosed malignant solid tumour Non-randomised dose expansion phase: female patients with histologically or cytologically diagnosed metastatic triple-negative breast cancer (platinum naive) and female patients with histologically or cytologically diagnosed ovarian cancer, where further treatment with platinum based chemotherapy is indicated. Randomised dose expansion phase: female patients with histologically or cytologically diagnosed measurable metastatic breast cancer and female patients with histologically or cytologically diagnosed measurable ovarian cancer, where further treatment with platinum based chemotherapy is indicated. 3. Adequate bone marrow, hepatic and renal function, including the following: a. hemoglobin >= 10.0 g/dl, ANC >= 1500x10 6/l, platelets >= 100.000x10 6/l; b. total bilirubin 60 ml/min) 5. Age >= 18 years 6. PS
Exclusion criteria
Exclusion criteria: 1. Any chemotherapy, radiotherapy (except for palliative reasons), endocrine therapy or immunotherpay within 4 weeks prior to study entry (or a longer period depending on the defined characteristics of the agents used). Patients may continue the use of biphosphonates for bone disease and corticosteroids provided the dose is stable before and during the study. Heavily pre-treated patients (> 2 courses of previous chemotherapy and/or extensive irradiation leading to bone marrow deficiency) will be excluded from the study. Bone marrow deficiency is defined as the occurence of one or other of the events below: - treatment delay in previous chemotherapy courses due to bone marrow toxicity. - previous chemotherapy courses requiring growth factor support. 2. Dose escalation phase: more than 2 previous courses of platinum-containing chemotherapy Non-randomised dose expansion phase: more than 2 courses of platinum-containing chemotherapy, except for metastatic triple negative breast cancer patients who must have had no previous platinum-containing chemotherapy. Randomised dose expansion phase: patients where platinum therapy is not indictaed 3. Major surgery within 4 weeks of starting the study and patients must have recovered from the effects major surgery. 4. Patients with an active second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix. An active second primary cancer is defined as one with a disease free interval of grade 1. 6. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study. 7. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol. 8. Symptomatic or known brain metastases. 9. Gastrointestinal disorders likely to interfere with absorption of the study drug. 10. Patients who are unable to swallow oral medication. 11. Patients with a history of allergic reactions to carboplatin, platinum containing compounds or mannitol. 12. Persistent toxicities (grade 2 or greater) from any cause. 13. Pregnant or breast-feeding women. 14. Patients with hepatic disease, e.g. patients with known serologically positive Hepatitis B or Hepatitis C as they may be more at risk of toxicity from KU-0059436. 15. Immunocompromised patients, e.g. patients who are known to be serologically positive for HIV. 16. Treatment with any investigational product during the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety data, including laboratory parameters and adverse events, will be collected for all patients in order to determine the toxicity, reversibility of toxicity, and dose limiting toxicity of orally administered KU-0059436 when given in combination with i.v. carboplatin, in combination with i.v. paclitaxel and carboplatin and in combination with i.v. paclitaxel. | — |
Secondary
| Measure | Time frame |
|---|---|
| Although tumour response is not the primary endpoint of this study, patients with measurable disease will be assessed by RECIST criteria. Pharmacokinetic data will also be collected. | — |
Countries
Netherlands
Outcome results
None listed