Capecitabine, Carboplatin and Weekly Paclitaxel for Patients With Solid Tumors and Adenocarcinoma of Unknown Primary

Study Overview
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Brief Summary
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This study will determine the maximum tolerated dose of the triplet combination of capecitabine that can be administered in combination with weekly paclitaxel and every four weeks with carboplatin.

Detailed Description
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Rationale: The combination of the chemotherapy drugs paclitaxel and carboplatin is one of the most common combination regimens used in clinical practice for cancer. These agents are used for a variety of cancers. The current study builds on previous research about treatment schedules for administering these agents to reduce toxicity and optimize efficacy. The phase I and II portions of the current study combine paclitaxel and carboplatin with capecitabine in patients. Researchers are seeking to identify the highest dose of capecitabine and paclitaxel in combination with carboplatin for this patient population, as well as to gather information about preliminary efficacy. Purpose: The phase I portion of this study will evaluate the maximum tolerated dose of capecitabine and paclitaxel in combination with carboplatin for patients. The phase II portion of this study will assess the objective response rate in patients using the same treatment combination. Toxicities will be closely measured in both phases of the study. Treatment: Patients in this study will be given capecitabine, carboplatin, and paclitaxel. Capecitabine will be given through oral pills. Carboplatin and paclitaxel will be given through intravenous infusions. Treatment drugs will be given on a four-week cycle. Carboplatin will be administered on day 1, paclitaxel weekly for the first 3 weeks, and capecitabine twice daily on days 8 through 21 of each cycle. No treatments will be given during the fourth week of each treatment cycle. During the phase I portion of the study, patients may receive different doses of capecitabine and paclitaxel since the purpose is to identify the maximum tolerated dose of each drug in combination with carboplatin. Once the maximum tolerated dose of these agents is identified during phase I, the phase II portion of the study will begin. Treatments will be discontinued due to disease growth or unacceptable side effects. Several tests and exams will be given throughout the study to closely monitor patients.

Official Title
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A Phase I Dose Escalation Study of Capecitabine, Carboplatin and Weekly Paclitaxel and a Phase II Trial of the Same Combination in Patients With Adenocarcinoma of Unknown Primary

Conditions
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Tumors, Unknown Primary Tumors, Adenocarcinoma

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Phase I: All advanced solid malignancies Any prior chemotherapy permitted Performance Status 0-2 Inclusion Criteria for Phase II: Adenocarcinoma of unknown primary No prior chemo permitted Performance Status 0-2

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: Arm I<br>Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, carboplatin IV over 1-2 hours on day 1, and capecitabine PO BID on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Capecitabine<br>* Level 1: 500 mg/m2 orally twice daily Days 8 - 21 of each cycle. Level 2: 750 mg/m2 orally twice daily Days 8 - 21 of each cycle. Level 3 - 5: 1000mg/m2 orally twice daily Days 8 - 21 of each cycle.<br>* Other names: Xeloda;Drug: Carboplatin<br>* Levels 1-5: AUC of 6 every 4 weeks.<br>* Other names: CBDCA;Drug: Paclitaxel<br>* Level 1-3: 60 mg/m2/week. Level 4: 80 mg/m2/week. Level 5: 100 mg/m2/week.<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose in Phase I Portion of Study | Determine the maximum tolerated dose of the triplet combination of capecitabine that can be administered in combination with weekly paclitaxel and every four weeks carboplatin. | Every 3 weeks, for up to 24 weeks | 
| Objective Response Rate (ORR) for the Phase II Portion of the Study. CR+PR Per RECIST v1.0 Criteria Using a Single Arm , Two Stage Minimax Design. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Every 3 weeks, for up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: To Determine Side Effects | The common clinically significant grade 3 and 4 toxicities graded using the National Cancer Institutes Common Toxicity Criteria version 3.0 | Every 3 weeks, for up to 24 weeks | 
| Progression-Free Survival at 6 Months for Patients | For patients enrolled on the Phase II portion of the trial Progression Free Survival (PFS) was measured from the percentage of patients that were still alive, without evidence of disease progression for 6 months following the initiation of treatment. 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 | up to 6 years | 
| One Year Survival for Patients | For patients enrolled on the Phase II portion of the trial the One-year survival was measured as the percentage of patients alive 1 year after their treatment in the trial. | Up to 1 year | 
| Time to Tumor Progression for Patients | For patients enrolled on the Phase II portion of the trial the time to progression was measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression or the date of death if the patient dies due to causes other than disease progression. | Up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenocarcinoma