Paricalcitol and Chemotherapy in Treating Women With Metastatic Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: paclitaxel; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: ixabepilone; Drug: paricalcitol

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: March 17, 2008
• First Submitted That Met QC Criteria: March 17, 2008
• First Posted (Estimate): March 18, 2008

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Docetaxel; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: CDR0000583652; P30CA012197 (U.S. NIH Grant/Contract); CCCWFU-74307 (Other Identifier: Comprehensive Cancer Center of WFUHS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No