Phase I/II Study of Dasatinib in Combination With Zoledronic Acid for the Treatment of Breast Cancer With Bone Metastasis

M.D. Anderson Cancer Center3 sites in 1 country31 target enrollmentNovember 1, 2007

ConditionsBreast Cancer Bone Metastases

InterventionsDasatinib Zoledronic Acid

DrugsDasatinib Zoledronic Acid

Overview

Phase: Phase 1
Intervention: Dasatinib
Conditions: Breast Cancer
Sponsor: M.D. Anderson Cancer Center
Enrollment: 31
Locations: 3
Primary Endpoint: Objective Response in Bone From Time of Initiation of Therapy to > 6 Months
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of dasatinib and Zometa (zoledronic acid) that can be given in combination for the treatment of breast cancer that has spread to the bone. The safety and effectiveness of this combination will also be studied.

Detailed Description

The Study Drugs: Zoledronic acid is designed to strengthen the bone and prevent fractures or breaks in the bone. Dasatinib is designed to block (stop) cells responsible for the breakdown of bone. Study Groups: If you are found to be eligible to take part in this study, you will be enrolled in a group of at least 3 participants to begin receiving zoledronic acid and dasatinib. The dose of dasatinib you receive will depend on when you enrolled in this study. All participants will receive the same amount of zoledronic acid. The first group of participants will be treated with the lowest dose of dasatinib given in combination with zoledronic acid. Once the highest tolerable dose level is found, up to 25 additional participants will be enrolled at that dose level. This is called the Phase II portion of the study. Drug Administration: You will receive zoledronic acid through a needle in your vein on Day 1 over 15 minutes. You will take dasatinib by mouth daily for 28 days. Dasatinib should be taken on an empty stomach or after a light meal. Every 28 days is called a study "cycle." Study Visits for Participants in the Phase I Portion: On Day 1 of Cycle 1, you will have the following tests and procedures performed. * You will have a physical exam, including measurement of your vital signs. * You will have a performance status evaluation. * Blood (about 1-2 teaspoons) will be drawn for routine tests. * You will have an ECG. On Day 8 of Cycle 1, you will have the following tests and procedures performed. * Blood (about 1-2 teaspoons) will be drawn for routine tests. * You will have an ECG. On Day 15 of Cycle 1, you will have the following tests and procedures performed. * You will have a physical exam. * You will have a performance status evaluation. * Blood (about 1-2 teaspoons) will be drawn for routine tests. * You will have an ECG. On Day 21 of Cycle 1, you will have the following tests and procedures performed. * Your vital signs will be measured. * Blood (about 1-2 teaspoons) will be drawn for routine tests. * You will have an ECG. On Day 1 of Cycle 2, you will have an ECG. On Day 1 of all other cycles, you will have the following tests and procedures performed. * You will have a physical exam. * You will have a performance status evaluation. * Blood (about 1-2 teaspoons) will be drawn for routine tests. * You will have MRIs, CT scans, and/or x-rays to check the status of the disease. On Days 1 and 28 of Cycle 1 and then every 3rd month, urine will be collected over 24 hours to check for markers of bone loss. After Cycles 3, 6, 9 and so on, you will have CT scans, MRIs, and/or x-rays to check the status of the disease At all study visits, you will be asked about any drugs you may be taking and any side effects you may be experiencing. Study Visits for Participants in the Phase II Portion: On Day 1 of all cycles, you will have the following tests and procedures performed. * You will have a physical exam, including measurement of your vital signs. * You will have a performance status evaluation. * Blood (about 1-2 teaspoons) will be drawn for routine tests. On Days 1 and 28 of Cycle 1 and then every 3rd month, urine will be collected to check for markers of bone loss. After Cycles 2, 4, 6 and so on, you will have CT scans, MRIs, and/or x-rays to check the status of the disease. At all study visits, you will be asked about any drugs you may be taking and any side effects you may be experiencing. Length of Study: You may remain on study for as long as you are benefitting. You will be taken off study if the disease gets worse or you experience intolerable side effects. End-of-Study Visit: Once you go off-study, you will have an end-of-study visit. * Your vital signs will be measured. * Blood (about 1-2 teaspoons) and urine will be collected for routine tests. * You will have MRIs, CT scans, and/or x-rays to check the status of the disease. This is an investigational study. Zoledronic acid is FDA approved and commercially available for the treatment of breast cancer. Dasatinib is not FDA approved or commercially available for the treatment of breast cancer. It has been authorized for use in research only. Up to 28 patients will take part in this multicenter study. Up to 12 will be enrolled at MD Anderson.

Registry

clinicaltrials.gov

Start Date

November 1, 2007

End Date

November 17, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

M.D. Anderson Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have a pathologically confirmed diagnosis of invasive carcinoma of the breast.
•Patients must carry a diagnosis of metastatic breast cancer with predominant bone involvement. For the purposes of this study, predominant bone involvement will be defined as radiographically detected bone metastasis in the presence or absence of other sites of metastatic breast cancer (i.e. visceral involvement). If visceral involvement is present, patients must be asymptomatic and have no tumors in visceral organs that measure \>3cm in size.
•Patients must agree to serial urine collections for measurement of Ntx.
•Age \>/= 18 years.
•Patients must be able to swallow oral medications. Dasatinib must be taken whole and cannot be crushed.
•Patients must have evaluable disease using WHO Criteria for Assessment of Disease Response in Bone or MDACC Modified Response Criteria for Assessment of Disease Response in Bone.
•Patients must not have had \>1 chemotherapy regimens for metastatic disease. Patients with metastasis diagnosed \</= 6 months after completion of adjuvant chemotherapy are considered to have had chemotherapy for metastatic breast cancer.
•Patients with ER positive disease must have had disease progression on at least one prior hormonal therapy for metastatic disease. Patients must also have developed disease progression on their most recent hormonal therapy regimen and be agreeable to continue this regimen in combination with protocol therapy. For the purposes of this study disease progression while receiving hormonal therapy will be defined as: Radiographic evidence of progressive disease according to RECIST criteria, Progression of disease by physical exam in patients with skin involvement. Continued in # 9
•Continuation from # 8: 25% increase in tumor marker as measured on two evaluations no less than 72 hours apart.
•Patients must have and ECOG performance status of \</=

Exclusion Criteria

•Any malignancy (other than breast cancer) that required radiotherapy or systemic treatment within the past 5 years.
•Concurrent medical condition which may increase the risk of toxicity, including: Pleural or pericardial effusion of any grade, clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand's disease)
•Cardiac Symptoms, including the following: Uncontrolled angina, congestive heart failure or MI within (6 months), diagnosed congenital long QT syndrome, any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), prolonged QTc interval on pre-entry electrocardiogram (\> normal range), subjects with hypokalemia or hypomagnesemia if it cannot be corrected
•History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), ongoing or recent (\</= 3 months) significant gastrointestinal bleeding
•Concomitant Medications, consider the following prohibitions (Drugs must be discontinued for 7 days prior to starting protocol therapy):
•Women and men of child bearing potential: who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or women of childbearing potential (CBP) who have a positive pregnancy test at baseline, or women who are pregnant or breastfeeding
•Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
•Untreated or uncontrolled brain metastasis
•Patient inability to take or absorb oral medications
•Current active dental problems including: ongoing infection of the teeth or jawbone (maxilla or mandibula); current exposed bone in the mouth; and current or prior diagnosis of osteonecrosis of the jaw

Arms & Interventions

Dasatinib + Zoledronic Acid

Dasatinib Phase I: First Cohort = 100 mg PO Daily x 28 days; Next Cohort = Dose Expansion or Reduction Based on Dose Limiting Toxicity (DLT) in Initial Cohort. Zoledronic Acid Phase I: First Cohort = 4 mg IV Over 15 min. every 4 Weeks; Next Cohort = Dose Expansion or Reduction Based on Dose Limiting Toxicity (DLT) in Initial Cohort. Phase II: Recommended Phase II Dose (RP2D) as determined with Phase I.

Intervention: Dasatinib