Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Carboplatin and/or Paclitaxel

Study Overview
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Brief Summary
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The purpose of this study is to identify a safe and tolerable dose of the drug KU-0059436 that can be given in combination with carboplatin and/or Paclitaxel chemotherapy.

Official Title
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A Phase I, Open-Label Study to Assess the Safety and Tolerability of KU-0059436 in Combination With Carboplatin, KU-0059436 in Combination With a Paclitaxel/Carboplatin T/C Doublet and KU-0059436 in Combination With Paclitaxel in the Treatment of Patients With Advanced Solid Tumours

Conditions
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Triple Negative Metastatic Breast Cancer, Advanced Ovarian Cancer, Carboplatin, Paclitaxel

Intervention / Treatment
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* Drug: KU-0059436 (AZD2281)(PARP inhibitor)
* Drug: Carboplatin
* Drug: KU-0059436 (AZD2281)(PARP inhibitor)
* Drug: Paclitaxel
* Drug: KU-0059436 (AZD2281)(PARP inhibitor)
* Drug: Paclitaxel + Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients with a histologically or cytologically diagnosed malignant solid tumour Adequate bone marrow, hepatic and renal function Performance status of no more than 2 ( ECOG scale). Exclusion Criteria: Any chemotherapy, radiotherapy ( except palliative), endocrine or immunotherapy within 4 weeks prior to entry Major surgery with 4 weeks of entering the study and must have recovered from effects of the major surgery More than two previous courses of platinum-containing chemotherapy Heavily pre-treated patients(> 2 courses of previous chemotherapy and/or extensive irradiation leading to bone marrow deficiency) will be excluded from the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Carboplatin + KU-0059436 | Drug: KU-0059436 (AZD2281)(PARP inhibitor)<br>* oral<br>* Other names: Olaparib;Drug: Carboplatin<br>* intravenous injection<br>* Other names: Paraplatin®;|
| Experimental: 2.<br>Paclitaxel + KU-0059436 | Drug: KU-0059436 (AZD2281)(PARP inhibitor)<br>* Oral<br>* Other names: Olaparib;Drug: Paclitaxel<br>* Intravenous injection<br>|
| Experimental: 3.<br>Paclitaxel, Carboplatin + KU-0059436 | Drug: KU-0059436 (AZD2281)(PARP inhibitor)<br>* Oral<br>* Other names: Olaparib;Drug: Paclitaxel + Carboplatin<br>* Intravenous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the maximum tolerated dose (MTD) of KU 0059436 in combination with Paclitaxel/Carboplatin |  | assessed at each visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify the dose limiting toxicity of the combination therapy |  | assessed at each visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malignant solid tumours, Poly(ADP ribose) polymerases