Safety of MP470 in Combination With Standard-of-Care Chemotherapy Regimens to Treat Solid Tumors

Study Overview
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Brief Summary
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Adult subjects with malignant disease appropriate for treatment with carboplatin/paclitaxel, carboplatin/etoposide, topotecan, docetaxel or erlotinib according to the standard dosing regimen will be enrolled in each treatment arm. Primary objective: Determine the MTD. Secondary objectives: Response rates, PK, quantify MP-470 on PK of SOC, and collect pharmacodynamic information. Evaluate the overall safety of MP-470 when co-administered with specific SOC treatments.

Official Title
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Safety and Dose Finding Study of Oral MP470, a Multi-targeted Tyrosine Kinase Inhibitor, in Combination With Standard-of-Care Chemotherapy Regimens

Conditions
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Malignant Disease

Intervention / Treatment
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* Drug: MP-470 + topotecan
* Drug: MP-470 + docetaxel
* Drug: MP-470 + erlotinib
* Drug: MP-470 + paclitaxel/carboplatin
* Drug: MP-470 + carboplatin/etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Malignant disease appropriate for initiating treatment with carboplatin/paclitaxel, carboplatin/etoposide, topotecan, docetaxel, or erlotinib. Must be able to read, understand, and sign the IRB approved Informed Consent Form. At least 18 years old. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Adequate bone marrow function; normal renal and hepatic function, normal cardiac function. Exclusion Criteria: Any other active invasive malignancy except non-melanoma skin cancers or cervical carcinoma in situ. History of significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure and/or myocardial infarction. Received any anticancer agent(s) within the past 3 weeks, including investigational agents, chemotherapy (6 weeks for nitrosoureas or mitomycin), immunotherapy, biologic or hormonal therapy other than LHRH agonists. Received prior radiation therapy within the past 4 weeks. Any serious, uncontrolled active infection that requires systemic treatment or known infection with HIV, HCV or HBV. Patient requires treatment with immunosuppressive agents other than corticosteroids appropriate for the SOC chemotherapy regimen or those at stable doses for at least 2 weeks.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>oral MP-470 + paclitaxel/carboplatin | Drug: MP-470 + paclitaxel/carboplatin<br>* Paclitaxel 200 mg/m2 IV infusion over 3 hours followed by carboplatin IV infusion over 1 hour to a target AUC of 6 mg∙min/mL on Day 1<br>|
| Experimental: 2<br>oral MP-470 + carboplatin/etoposide | Drug: MP-470 + carboplatin/etoposide<br>* Carboplatin IV infusion over 1 hour to target AUC of 5 mg min/mL on Day 1 followed by etoposide 100 mg/m2 IV infusion over 2 hours on Days 1-3<br>|
| Experimental: 3<br>oral MP-470 + topotecan | Drug: MP-470 + topotecan<br>* Topotecan 1.5 mg/m2 IV infusion over 30 minutes on Days 1-5<br>|
| Experimental: 4<br>oral MP-470 + docetaxel | Drug: MP-470 + docetaxel<br>* Docetaxel 75 mg/m2 IV infusion over 1 hour on Day 1<br>|
| Experimental: 5<br>oral MP-470 + Erlotinib | Drug: MP-470 + erlotinib<br>* 150 mg PO once daily at least 1 hour before or 2 hours after eating<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) |  | March 2010 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | March 2010 | 
| Pharmacokinetics, pharmacodynamic effects on biomarker modulation. |  | March 2010 | 
| Experience DLT |  | March 2010 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MP-470, Multi-targeted Tyrosine Kinase Inhibitor, Malignant disease