Study Assessing Safety and Tolerability of AZD8931 Alone or in Combination With Paclitaxel in Japanese Patients.

Study Overview
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Brief Summary
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The main purpose of this study is to determine if AZD8931 can be safely administered in Japanese patients alone and in combination with weekly paclitaxel. The study will be conducted in two parts: a monotherapy and a combination part, where safe doses of study treatment will be determined.

Official Title
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A Phase I, Open-label, Multiple-dose, Dose-escalation Study To Assess the Safety and Tolerability of AZD8931 Monotherapy in Japanese Patients With Advanced Solid Malignancies and in Combination With Paclitaxel in Japanese Female Patients With Advanced Breast Cancer

Conditions
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Neoplasms, Metastatic Cancer, Breast Cancer

Intervention / Treatment
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* Drug: AZD8931
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cancer that is refractory to standard therapies, or for which no standard therapies exist (monotherapy part) Patients suitable for Paclitaxel chemotherapy, who are not candidates for hormonal and anthracycline therapy (combination part) Life expectancy more than 12 weeks Exclusion Criteria: Inadequate kidney, liver, heart, gastric, lung or eye function Brain metastases Hypersensitive to paclitaxel (combination part)

Ages Eligible for Study
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Minimum Age: 20 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: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy part<br>AZD8931 monotherapy | Drug: AZD8931<br>* Tablet Oral bid<br>|
| Experimental: Combination part<br>AZD8931 plus paclitaxel | Drug: AZD8931<br>* Tablet Oral bid<br>Drug: Paclitaxel<br>* IV once weekly for 3 weeks followed by a week off<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monotherapy part: Assessment of adverse events, laboratory findings, physical examination, vital signs, ECG/UCG, chest X-ray, HRCT, SpO2 and ophthalmological examinations. |  | Full routine safety assessment on days 1-4, 8, 10, 14, 21, 28 then every 3 weeks after first dose of study drug | 
| Combination part: The contents of same assessment as Monotherapy. |  | Full routine safety assessment on days 1-5, 8, 15, 22, 28 then every 4 weeks after first dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combination Part: Pharmacokinetics of AZD8931 (tmax, Cmax, AUC0-10) |  | On Day D7 and Day D8: pre-dose then, 1, 2, 4, 6, 8 and 10 hours post dose | 
| Combination Part: Pharmacokinetics of paclitaxel (tmax, Cmax, AUC0-10) |  | On Days D1 and Day D8: pre-infusion then, 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 24 (D1 only) hours post start of infusion | 
| Monotherapy Part: Pharmacokinetics of AZD8931 (Single dose plasma PK: AUC0-10, AUC0-12, AUC0-24, AUC0-t, AUC, Cmax, tmax, t1/2, CL/F, Vss/F. Multiple dose plasma PK: AUCss0-10, AUCss0-12, Cssmax, tssmax, Cssmin, CLss/F, RAC, linearity factor) |  | On single dose Day 1 (D1) and multiple dose Day 21 (R14): samples taken pre-dose then 1, 2, 4, 6, 8, 10, 24 (D1 only), 48 (D1 only) and 72 (D1 only) hours post dose. Day 10 (R3) and Day 14 (R7): pre-dose only | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, tumour, metastatic, breast cancer