Phase I AZD2281/Cisplatin in Advanced Solid Tumour Patients

Study Overview
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Brief Summary
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A Phase I study to assess the safety and tolerability of AZD2281 in combination with Cisplatin in patients with advanced Solid Tumours. This is an open label-dose finding; to establish the maximum tolerated dose of AZD2281 combined with Cisplatin in patients with advanced solid tumours. Approximately 50 (max 60) patients from 2 countries will be enrolled

Official Title
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A Phase I Open Label, Multi Centre Study of AZD2281 Administered Orally in Combination With Cisplatin, to Assess the Safety and Tolerability in Patients With Advanced Solid Tumours

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: AZD2281
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Life expectancy of at least 12 weeks Histologically confirmed metastatic cancer, not amenable to surgery or radiation therapy with curative intent Patients with measurable or non measurable disease according to RECIST Exclusion Criteria: Less than 28 days from active therapy (ie any treatment used to treat the disease) or high dose radiotherapy Brain Metastases or spinal cord compression unless irradiated at least 4 weeks before entry and stable without steroid treatment for >1 week Persistent CTCAE Grade 2 or greater toxicities (excluding alopecia) caused by prior therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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>Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose recommended by Investigator. Full dose: 300 mg twice daily (bid) or Reduced doses: 200 mg twice daily (bid) or 100 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions. | Drug: AZD2281<br>* Tablets Oral BID<br>* Other names: Olaparib; Lynparza;Drug: Cisplatin<br>* IV every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and tolerability of AZD2281 in combination with Cisplatin (eg Adverse Events, Pharmacokinetic for AZD2281, overall response rate) to patients with advanced solid tumours. |  | Weekly visits for routine monitoring visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare exposure to AZD2281 when given alone and in combination with Cisplatin (Only in patients receiving continuous dosing of AZD2281). |  | PK samples taken at visit 2 and 3 | 
| To make a preliminary assessment of the anti-tumour activity of AZD2281 when given in combination with Cisplatin, by measuring overall objective response rate. |  | Assessed at screening, visit 9, and at end of every 2 cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BRCA1, Advanced solid tumours, Poly(ADP ribose) polymerases, homologous deficiency