Paclitaxel/Carboplatin Plus Bevacizumab/Erlotinib in the First Line Treatment of Carcinoma of Unknown Primary Site

Study Overview
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Brief Summary
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We will evaluate the feasibility, toxicity, and effectiveness of combination chemotherapy (paclitaxel/carboplatin)plus combination targeted therapy (bevacizumab/erlotinib)in the first line treatment of patients with carcinoma of unknown primary site. There is limited experience with either bevacizumab or erlotinib in the treatment of cancers of unknown site but given the heterogeneous nature of the tumor, it is likely that inhibition of angiogenesis pathways and/or the EGFR pathway are effective strategies in at least a proportion.

Detailed Description
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All eligible patients will receive: Bevacizumab 15mg/kg IV infusion,Day 1 Paclitaxel 175mg/m2, 1-3 hour IV infusion,Day 1 Carboplatin AUC 6.0 IV Day 1 Erlotinib 150 mg by mouth daily The regimen will be repeated every 21 days for a total of 4 courses. Patients will be initially evaluated for response after completing 2 courses (6 weeks) of treatment. Patients with an objective tumor response or stable disease will continue treatment for another 2 courses. Patients will be re-evaluated after 4 courses and those with objective tumor response or stable disease will stop chemotherapy with paclitaxel/carboplatin and continue treatment with bevacizumab/erlotinib until tumor progression is documented for a maximum of 12 months. During treatment with bevacizumab/erlotinib response will be evaluated every 12 weeks.

Official Title
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A Phase II Study of Paclitaxel/Carboplatin Plus Bevacizumab/Erlotinib in the First Line Treatment of Patients With Carcinoma of Unknown Primary Site

Conditions
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Neoplasm, Unknown Primary

Intervention / Treatment
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* Drug: paclitaxel
* Drug: carboplatin
* Drug: bevacizumab
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven metastatic carcinoma with the following light microscopic histologies: adenocarcinoma, poorly differentiated carcinoma(must have immunoperoxidase stains to rule out lymphoma, neuroendocrine carcinoma),or poorly differentiated squamous carcinoma. ECOG performance status 0-1 No previous treatment with any systemic therapy Adequate kidney, liver and bone marrow function Be able to understand the nature of the study and give written informed consent Exclusion Criteria: The following specific syndromes: Neuroendocrine carcinoma Women with adenocarcinoma isolated to axillary lymph nodes Women with adenocarcinoma isolated to peritoneal involvement Carcinoma involving only one site with resectable tumors at that site Squamous carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes Uncontrolled brain metastases and all patients with meningeal involvement Women pregnant or lactating Clinically significant cardiovascular disease History of myocardial infarction or stroke within 6 months Clinical history of hemoptysis or hematemesis Patients with PEG tubes or G-tubes Proteinuria History of bleeding diathesis or coagulopathy Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab/Paclitaxel/Carboplatin/Erlotinib<br>Bevacizumab 15mg/kg IV infusion,Day 1 Paclitaxel 175mg/m2, 1-3 hour IV infusion,Day 1 Carboplatin AUC 6.0 IV Day 1 Erlotinib 150 mg by mouth daily | Drug: paclitaxel<br>* Paclitaxel 175mg/m2, 1-3 hour IV infusion,Day 1<br>* Other names: Taxol;Drug: carboplatin<br>* Carboplatin AUC 6.0 IV Day 1<br>* Other names: Paraplatin;Drug: bevacizumab<br>* Bevacizumab 15mg/kg IV infusion,Day 1<br>* Other names: Avastin;Drug: erlotinib<br>* Erlotinib 150 mg by mouth daily<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasm, Unknown Primary