A Phase 2 Feasibility Study of Abraxane and Carboplatin in Epithelial Neoplasms of the Uterus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of treatment with carboplatin and Abraxane in this patient population and determine the nature and degree of toxicities following treatment. The single stage open label Phase II feasibility study is designed to estimate the proportion of patients who can tolerate the proposed regimen for 6 cycles with no more than two dose level reductions.

Official Title
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A Phase 2 Feasibility Study of Abraxane and Carboplatin in Epithelial Neoplasms of the Uterus

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: Carboplatin AUC
* Drug: Abraxane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients must have high risk resected stage I disease (papillary serous histology, clear cell histology or carcinosarcoma), advanced stage (III or IV, all histologies) or recurrent endometrial cancer (all histologies). Patients do not need measurable disease and can enroll following surgery. Patients may not have received prior cytotoxic chemotherapy. However, nonplatinum/non-taxane chemotherapy used for radiation sensitization is allowed. Patients may have received prior radiation therapy (including whole pelvic or vaginal brachytherapy), hormonal therapy, or therapy with biologic agents, but such therapy must be discontinued at least 2 weeks prior to entry on this study. If patients underwent surgery, and chemotherapy is indicated after surgery either as adjuvant or to treat residual disease, study treatment should be initiated within 8 weeks of surgery. In patients who have received prior radiation, at least 4 weeks should have elapsed since the completion of radiation therapy involving the whole pelvis or over 50% of the spine. If vaginal brachytherapy is planned with chemotherapy, it should be done before or after completion of chemotherapy treatment. Poorly differentiated histology, uterine papillary serous carcinoma, clear cell carcinoma or carcinosarcoma is acceptable as long as the predominant metastatic component is epithelial (versus sarcomatous). Patients may have synchronous endometrial and ovarian cancer primaries. Patients must have a GOG performance status of 0, 1, or 2 Patients must be at least 18 years of age. Patients must understand and willingly sign an approved informed consent, and authorization permitting release of personal health information. Patients must have adequate liver function: AST and ALT ≤ 2.5 X upper limit of normal (ULN), and bilirubin ≤ 1.5mg/dL. Patients must have adequate bone marrow function: platelets ≥ 100,000 cells/mm3 (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample), hemoglobin > 9.0g/dl and ANC ≥ 1,500 cells/mm3. Patients must have adequate renal function: creatinine < 1.5 mg/dL is recommended; however, institutional norms are acceptable. Patients must have < grade 2 pre-existing peripheral neuropathy (per CTCAE). Exclusion Criteria: Other prior malignancies within 3 years, except non-melanoma skin cancers and synchronous ovarian primaries. Eligibility to a higher priority trial for first line or recurrent endometrial cancer (unless patient is unwilling to participate in such a trial). Patients with concomitant medical illness such as serious uncontrolled infection, or uncontrolled angina, which in the opinion of the treating physician, make the treatments prescribed on this study unreasonably hazardous for the patient. Patients who are pregnant or breastfeeding. Patients with third degree or complete heart block are not eligible unless a pacemaker is in place. Patients on medications, which alter cardiac conduction, such as digitalis, beta-blockers, or calcium channel blockers, or who have other conduction abnormalities or cardiac dysfunction could be entered at the discretion of the investigators. Patients with history of myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure or symptoms suspicious for congestive heart failure are not eligible unless a LVEF in the past 6 months is documented to be 50% or greater. Patients who have had a LVEF (performed for any reason) that is less than 50% in the past 6 months are ineligible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Carboplatin AUC and Abraxane 100mg/m2<br> | Drug: Carboplatin AUC<br> <br> Drug: Abraxane<br>* 100mg/m2<br>* Other names: Paclitaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability Measured Completion of Dose Regimen | Tolerability for an individual patient will be defined as remaining on the study for 6 cycles with two or fewer dose reductions. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at Month 24 | PFS is defined as the time from first dosing to the first observation of disease progression or death due to any cause. PFS was estimated beyond the collected data using Kaplan Meier methods. | Up to Month 24 | 
| Objective Response Rate (ORR) as Measured by RECIST 1.1 at Month 24 | ORR is the number of patients whose best tumor response outcome by Month 24 is a Complete Response (CR) or Partial Response (PR), divided by the total number of evaluable patients. Per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1.): CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD | Up to Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uterus, gynecological, corpus uteri