A Phase I/II Clinical Trial of Vidaza With Abraxane in Patients With Advanced/Metastatic Solid Tumors and Breast Cancer

Study Overview
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Brief Summary
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The purpose of this clinical trial is to test whether treatment of patients with advanced or metastatic solid tumors or breast cancer with Abraxane plus Vidaza is safe and results in good tumor response. All patients enrolling in this study will receive treatment with Abraxane and Vidaza. Safety will be assessed by adverse events, laboratory results and performance status. Tumor response will be measured by RECIST criteria.

Detailed Description
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The phase I part of the study will enroll patients with advanced or metastatic solid tumors who have failed at least one previous treatment. The purpose of the phase I part is to assess the safety of the investigational treatment and select the recommended phase II dose-regimen. The phase II part of the study will enroll patients with advanced or metastatic HER2-negative breast cancer who have not received treatment for their metastatic disease. The purpose of the phase II part of the study is to assess safety and efficacy of the investigational treatment in breast cancer. The study doctor will determine what phase patients will be enrolled in.

Official Title
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A Phase I/II Clinical Trial of the Hypomethylating Agent Azacitidine (Vidaza) With the Nanoparticle Albumin Bound Paclitaxel (Abraxane) in the Treatment of Patients With Advanced or Metastatic Solid Tumors and Breast Cancer

Conditions
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Advanced or Metastatic Solid Tumors, Advanced or Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Azacitidine (Vidaza)
* Drug: Nab-paclitaxel (Abraxane)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For phase I, any solid tumors, including lymphoma, that progressed or were stable as best response on at least one previous therapy and are evaluable. For phase II, pathologically confirmed breast cancer, measurable disease, no prior treatments for recurrent or metastatic breast cancer. Her-2/neu negative (Phase II) Negative pregnancy test for female subjects Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine or nab-paclitaxel. investigator. Male or female for phase I and female for phase II, >19 years of age and any race. Exclusion Criteria: Major surgery, radiotherapy, chemotherapy or investigational agents within 4 weeks of treatment day 1 Known brain metastases Prior taxanes (except for adjuvant therapy more than 6 months prior to treatment day 1) (phase II) Active infection requiring antibiotic therapy History of allergy or hypersensitivity to nab-paclitaxel, albumin or a taxane Grade 2 or greater motor or sensory neuropathy Prior cytotoxic chemotherapy for recurrent or metastatic breast cancer (phase II portion) Uncontrolled hypertension, arrhythmia, congestive heart failure or angina. Patients who have had a myocardial infarction or cardiac surgery should be at least 6 months from the event and free of active symptoms. Known or suspected hypersensitivity to azacitidine or mannitol Pregnant or breast feeding Patients with advanced malignant hepatic tumors Malignancy other than breast carcinoma (phase II) Known HIV infection or chronic hepatitis B or C

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: All patients<br>All participants enrolled. | Drug: Azacitidine (Vidaza)<br>* 50mg/m2, 75mg/m2 or 100mg/m2 daily for 5 days for each 4-week cycle<br>* Other names: Vidaza;Drug: Nab-paclitaxel (Abraxane)<br>* 100mg/m2 weekly for 3 weeks of each 4-week cycle<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Percentage of Participants Responding to Treatment | Azacitidine is set at 75mg/m2 and Nab-paclitaxel is set at100mg/m2 based on the number of participants responding to treatment as measured per RECIST v1 criteria. | 6 months | 
| Phase II: Percentage of Participants With Objective Response Rate (ORR) Measured Using RECIST 1.0 Criteria | Objective response rate (ORR) will be measured using RECIST 1.0 criteria. The best response, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), for each patient will be summarized. For target lesions, Complete Response is defined as disappearance of all target lesions for at least 4 weeks; Partial Response consists of at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, for at least 4 weeks; Progressive Disease consists of at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease consists of neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With ER+ Status | Tissue SPARC protein will be assessed using archival tumor blocks. In addition, in patients who have easily accessible tumors, such as lymph nodes, cutaneous or subcutaneous lesions, and who have consented to sample collection, biopsies will be taken twice: before cycle 1 day 1 treatment, and cycle 3 day 8 (+/- 3 days). | 2 years | 
| Progression-free Survival | Progression-free survival (PSF) is defined as the length of time during and after treatment in which a patient is living with a disease that does not get worse. | 2 years |