Paricalcitol and Chemotherapy in Treating Women With Metastatic Breast Cancer

Wake Forest University (WFU)

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Treatments

Drug: ixabepilone

Drug: paclitaxel

Drug: paricalcitol

Drug: paclitaxel albumin-stabilized nanoparticle formulation

Drug: docetaxel

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00637897

P30CA012197 (U.S. NIH Grant/Contract)

CCCWFU-74307 (Other Identifier)

CDR0000583652

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

Female

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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