CP-868,596 And CP-868,596 Plus AG-013736 In Combination With Docetaxel In Advanced Solid Tumors

Study Overview
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Brief Summary
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A5301005 is a phase 1 study in patients with solid tumors which is testing the safety and tolerability of adding targeted agents to a standard chemotherapy. CP-868,596 is a platelet-derived growth factor receptor inhibitor (PDGFR) and AG-13736 is a vascular endothelial growth factor receptor inhibitor (VEGFR). This study will test the use of docetaxel (the standard chemotherapy) with either CP-868,596 or the combination of CP-868,596 and AG-13736.

Official Title
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Phase I Study To Determine The Maximally Tolerated Dose Of Oral, Daily CP-868,596 And CP-868,596 Plus AG-013736 When Given In Combination With Docetaxel Administered Every 3 Weeks To Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: CP-868,596
* Drug: Docetaxel
* Drug: CP-868,596
* Drug: Docetaxel
* Drug: CP-868,596
* Drug: Docetaxel
* Drug: CP-868,596
* Drug: AG-013736
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be ≥18 years old and with histologically or cytologically confirmed advanced solid tumors refractory/resistant to currently available therapies or for which there is no standard therapy. Patients with primary brain tumors are not eligible. Have at least one site of measurable disease. Exclusion Criteria: Received chemotherapy (including targeted agents such as erlotinib), radiotherapy, immunotherapy or any investigational therapy within 3 weeks of study entry (within 6 weeks for previous treatments with nitrosoureas or mitomycin C). Received tamoxifen within 4 weeks prior to study entry.

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: Cohort 1<br>60 mg BID/ 75 mg/m2 | Drug: CP-868,596<br>* Oral tablet 60 mg BID continuous<br>Drug: Docetaxel<br>* Intravenous 75 mg/m2 every three weeks<br>|
| Experimental: Cohort 2<br>100 mg BID/75 mg/m2 | Drug: CP-868,596<br>* Oral tablet 100 mg BID continuous<br>Drug: Docetaxel<br>* Intravenous 75 mg/m2 every three weeks<br>|
| Experimental: Cohort 3<br>100 mg BID/100 mg/m2 | Drug: CP-868,596<br>* Oral tablet 100 mg BID continuous<br>Drug: Docetaxel<br>* Intravenous 100 mg/m2 every three weeks<br>|
| Experimental: Cohort 4b<br>CP-868,596 + AG-013736 + TXT 75 | Drug: CP-868,596<br>* Oral tablet 60 mg BID continuous<br>Drug: AG-013736<br>* Oral tablet 5 mg BID continuous<br>Drug: Docetaxel<br>* Intravenous 75 mg/m2 every three weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First-cycle Dose Limiting Toxicities |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the safety and tolerability of the combination of daily CP-868,596 and docetaxel on an every 3-week schedule |  | 2.5 years | 
| Determine the safety and tolerability of the combination of daily CP-868,596 plus daily AG-013736 plus docetaxel on an every 3-week schedule |  | 2.5 years | 
| To evaluate the pharmacokinetics (PK) of CP-868,596 and docetaxel when given in combination |  | 2.5 years | 
| To evaluate the pharmacokinetics (PK) of CP-868,596, AG-013736 and docetaxel when given in combination |  | 2.5 years | 
| Conduct biomarker investigations on plasma/serum samples to explore critical events in pharmacodynamic response to CP-868,596 (eg, VEGF, phospho-SHP, etc.) |  | 2.5 years | 
| To explore the relationship between polymorphisms in genes involved in the metabolism and transport of CP-868,596 and pharmacokinetic/pharmacodynamic parameters |  | 2.5 years | 
| To explore the effects of CP-868,596 on tumor blood flow and permeability via DCE-MRI |  | 2.5 years | 
| To assess any preliminary clinical evidence of anti-tumor activity using RECIST |  | 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDGFr Inhibition;, VEGFr inhibition;, targeted therapy