Phase I, Open-label, Dose-escalation, Safety and PK Study of AZD6918

Study Overview
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Brief Summary
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The primary purpose of this study is to find out what the maximum tolerated dose is for an experimental drug called AZD6918 based on the side effects experienced by patients with advanced solid malignancies that receive daily AZD6918 alone. It is possible that AZD6918 will be administered twice daily. Then maximum tolerated doses in combination with either gemcitabine or pemetrexed will also be investigated.

Official Title
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A Phase I, Open-Label, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6918 Administered Daily as a Single Agent and in Combination Treatment in Adult Patients With Refractory Solid Malignancies

Conditions
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Cancer,, Solid Tumors, Advanced Solid Malignancies

Intervention / Treatment
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* Drug: AZD6918
* Drug: gemcitabine
* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced solid tumors for which standard treatment does not exist or is no longer effective. For chemotherapy combination treatment, must be suitable for treatment with either gemcitabine or pemetrexed. Relatively good overall health other than cancer. Exclusion Criteria: Poor bone marrow function (not producing enough blood cells). Poor liver or kidney function. Serious heart conditions History of uncontrolled epilepsy, Parkinson's disease, Alzheimer's disease, brain tumor or any uncontrolled psychiatric or nervous system condition

Ages Eligible for Study
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Minimum Age: 18 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: gemcitabine<br>gemcitabine administered in combination with AZD6918 | Drug: gemcitabine<br>* intravenous, doses are on an intermittent schedule<br>* Other names: Gemzar;|
| Experimental: pemetrexed<br>pemetrexed administered in combination with AZD6918 | Drug: pemetrexed<br>* intravenous, dose administered every 21-days<br>* Other names: Alimta;|
| Experimental: AZD6918<br>AZD6918 administered alone | Drug: AZD6918<br>* liquid suspension, daily, oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events (based on CTCAE version 3.0), laboratory values, vital sign measurements, Karnofsky performance status |  | Weekly for first two treatment cycles, then every 2-4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic effect of AZD6918 when administered alone and in combination with chemotherapy |  | According to protocol specified schedule, the number of PK samples collected during Cycle 1 (up to 28 days) based on treatment with AZD6918 alone or in combination with chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I,, cancer,, solid tumors,, advanced solid malignancies,, dose escalation,, combination treatment,, TRK inhibitor