Paricalcitol and Chemotherapy in Treating Women With Metastatic Breast Cancer

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT00637897

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: docetaxel Drug: ixabepilone Drug: paclitaxel Drug: paclitaxel albumin-stabilized nanoparticle formulation Drug: paricalcitol	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Nov 1, 2011

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paricalcitol (Zemplar) Paricalcitol (Zemplar)	Drug: docetaxel Drug: ixabepilone Drug: paclitaxel Drug: paclitaxel albumin-stabilized nanoparticle formulation Drug: paricalcitol

Arm

Intervention/Treatment

Experimental: Paricalcitol (Zemplar)

Paricalcitol (Zemplar)

Drug: docetaxel

Drug: ixabepilone

Drug: paclitaxel

Drug: paclitaxel albumin-stabilized nanoparticle formulation

Drug: paricalcitol

Outcome Measures

Primary Outcome Measures

Clinical feasibility of therapy administration [Baseline to 8 weeks]
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

Secondary Outcome Measures

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 [Baseline to 8 weeks]
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
Measurement of effect of combination of paricalcitol and a taxane or ixabepilone on parathyroid hormone levels failure [Baseline to 8 weeks]
To determine if parathyroid hormone levels decline from baseline with the combination of paricalcitol and a taxane or ixabepilone

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096

Sponsors and Collaborators

Wake Forest University Health Sciences
National Cancer Institute (NCI)

Investigators

Study Chair: Julia A. Lawrence, Wake Forest University Health Sciences
Principal Investigator: Susan A. Melin, MD, Wake Forest University Health Sciences