Paricalcitol and Chemotherapy in Treating Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, docetaxel,, paclitaxel, and ixabepilone work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Paricalcitol may help chemotherapy drugs to kill more tumor cells by making tumor cells more sensitive to the drugs. PURPOSE: This clinical trial is studying the best dose and best way to give paricalcitol and to see how well it works when given together with chemotherapy in treating patients with metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary To determine the ability to administer 8 continuous weeks of therapy within the first 3 months of enrollment with paricalcitol when given together with taxane or ixabepilone therapy in women with metastatic breast cancer. To estimate the proportion of patients who successfully complete 8 continuous weeks of therapy as well as the proportion of patients who achieve a 'steady-state' dose. Secondary To determine a dose of paricalcitol that can be taken continuously that maintains a normal calcium level when combined with a taxane or ixabepilone. To determine if baseline levels of 25-hydroxycholecalciferol and parathyroid hormone (PTH) are associated with time to treatment failure in these patients. To determine if PTH levels decline from baseline in patients treated with paricalcitol in combination with taxane or ixabepilone therapy. OUTLINE: Beginning on day 1, patients receive oral paricalcitol. The dose of paricalcitol is increased every 2 weeks until the serum calcium level is between 9 mg/dL and 11.4 mg/dL. Once this level is reached, the patient continues at that dose for the duration of the study. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation, docetaxel, or paclitaxel once a week or once every 3 weeks or ixabepilone once every 3 weeks. Treatment continues for at least 12 weeks in the absence of disease progression or unacceptable toxicity.

Official Title
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Feasibility of Dose Titrating Paricalcitol (Zemplar) in Women Receiving Taxanes or Ixabepilone for Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: docetaxel
* Drug: ixabepilone
* Drug: paclitaxel
* Drug: paclitaxel albumin-stabilized nanoparticle formulation
* Drug: paricalcitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically confirmed invasive breast cancer Metastatic or recurrent disease Patients with bone metastasis only are eligible and evaluable for time to progression Candidate for taxane or ixabepilone therapy At least one lesion that can be measured in at least one diameter ≥ 2 cm by CT scan No symptomatic brain metastases or other symptomatic CNS metastases ECOG performance status 0 or 1 Life expectancy > 3 months ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL Serum creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 2.0 g/dL Albumin corrected serum calcium < 10.5 mg/dL Fertile patients must use effective contraception during and for at least 1 year after study participation At least 2 weeks since prior chemotherapy or radiation therapy Prior and concurrent taxane or ixabepilone therapy allowed Concurrent oral multivitamins allowed (i.e., Centrum or One a Day) Concurrent bisphosphonates allowed Exclusion Criteria History of allergy to calcitriol, paricalcitol, or other Vitamin D compounds History of drug or alcohol abuse within the past 6 months History of other malignancy except inactive nonmelanoma skin cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or other cancer if the patient has been disease-free for 5 or more years Serious medical illness that would limit survival to < 3 months Active, uncontrolled bacterial, viral or fungal infection Poorly controlled diabetes Concurrent supplemental calcium Concurrent digitalis compounds Concurrent chemotherapy Concurrent biologic therapy, including trastuzumab and bevacizumab Concurrent hormonal agents for breast cancer except luteinizing hormone-releasing hormone agonists

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Paricalcitol (Zemplar)<br>Paricalcitol (Zemplar) | Drug: docetaxel<br> <br> Drug: ixabepilone<br> <br> Drug: paclitaxel<br> <br> Drug: paclitaxel albumin-stabilized nanoparticle formulation<br> <br> Drug: paricalcitol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical feasibility of therapy administration | To test the clinical/logistical feasibility of using a titrated dose of the vitamin D analog (paracalcitol or Zemplar) in combination with a taxane or ixabepilone primarily by measuring the proportion of patients who successfully complete 8 continuous weeks of therapy as well as the proportion of patients who achieve a 'steady-state' dose | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose of paricalcitol that maintains a normal calcium level when given in combination with a taxane or ixabepilone |  | Baseline to 8 weeks | 
| Correlation of baseline levels of 25-hydroxycholecalciferol and parathyroid hormone with time to treatment failure | To determine if baseline levels of 25(OH)D and parathyroid hormone are associated with time to treatment failure in patients treated with the combination of paricalcitol and a taxane or ixabepilone | Baseline to 8 weeks | 
| Measurement of effect of combination of paricalcitol and a taxane or ixabepilone on parathyroid hormone levels failure | To determine if parathyroid hormone levels decline from baseline with the combination of paricalcitol and a taxane or ixabepilone | Baseline to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer