A Phase I, Open label Study to Assess the Safety and Tolerability of KU-0059436 in Combination with Carboplatin and of KU-0059436 in Combination with a Paclitaxel/Carboplatin (TC) doublet and KU-0059436 in combination with Paclitaxel in the Treatment of Patients with Advanced Solid Tumours
- Conditions
- matastatic diseasesolid tumours10027655
- Registration Number
- NL-OMON46952
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 200
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 <= 1,25 x upper normal limit
c. AST (SGOT), ALT (SGPT) ,= 2,5 x upper normal limit
d. creatinine <= 1,5 x upper normal limit
4. Creatinine clearance (Cockcroft-Gault) within normal range (> 60 ml/min)
5. Age >= 18 years
6. PS <= 2
7. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days of start of study.
8. The patient is willing to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
9. Life expectancy of at least 12 weeks.
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 <3 years
5. Pre-existing peripheral neuropathy > 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety data, including laboratory parameters and adverse events, will be<br /><br>collected for all patients in order to determine the toxicity, reversibility of<br /><br>toxicity, and dose limiting toxicity of orally administered KU-0059436 when<br /><br>given in combination with i.v. carboplatin, in combination with i.v. paclitaxel<br /><br>and carboplatin and in combination with i.v. paclitaxel.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Although tumour response is not the primary endpoint of this study, patients<br /><br>with measurable disease will be assessed by RECIST criteria. Pharmacokinetic<br /><br>data will also be collected.</p><br>