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Dasatinib in Combination With Zoledronic Acid for the Treatment of Breast Cancer With Bone Metastasis

This study is ongoing, but not recruiting participants.
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: November 29, 2007
Last updated: December 8, 2016
Last verified: December 2016
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.

Condition Intervention Phase
Breast Cancer
Bone Metastases
Drug: Dasatinib
Drug: Zoledronic Acid
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Dasatinib in Combination With Zoledronic Acid for the Treatment of Breast Cancer With Bone Metastasis

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) for Dasatinib in Combination with Zoledronic Acid [ Time Frame: 28 days ]

    If at least 2 of 3 patients treated within a given dosing cohort develop dose limiting toxicity (DLT), it can be concluded with 90% confidence that the true probability of DLT at that dose is greater than 20%. If none of the 3 patients demonstrates DLT, it can be concluded with 90% confidence that the true probability of DLT is less than 55%.

    Toxicity assessed using the NCI Common Toxicity Criteria (CTC) Scale, version 3.0.

Secondary Outcome Measures:
  • Response Rate of Dasatinib in Combination with Zoledronic Acid [ Time Frame: 56 days after the start of Phase II ]
    Trial conducted by the Simon's two-stage design using the minimax criterion and response rate estimated accordingly.

Estimated Enrollment: 28
Study Start Date: November 2007
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: 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.

Phase II: Recommended Phase II Dose (RP2D) as determined with Phase I.

Other Names:
  • BMS-345825
  • Sprycel®
Drug: 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.

Other Names:
  • Zoledronate
  • Zometa®

  Show Detailed Description


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have a pathologically confirmed diagnosis of invasive carcinoma of the breast.
  2. 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.
  3. Patients must agree to serial urine collections for measurement of Ntx.
  4. Age >/= 18 years.
  5. Patients must be able to swallow oral medications. Dasatinib must be taken whole and cannot be crushed.
  6. 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.
  7. 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.
  8. 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
  9. Continuation from # 8: 25% increase in tumor marker as measured on two evaluations no less than 72 hours apart.
  10. Patients must have and ECOG performance status of </= 2.
  11. Patients must not require concurrent radiation or chemotherapy while receiving protocol therapy.
  12. Patients must not have an active infection requiring the use of intravenous antibiotics. The use of oral antibiotics as prophylaxis is allowed.
  13. Patients must have a baseline ECG with QTc within the normal range within 28 days prior to registration.
  14. Patients must be informed of the investigational nature of the study and must sign and give written informed consent.
  15. Patients may have received previous radiation but must have completed radiation at least 2 weeks (8 weeks for radiation to the brain) prior to registration. Patients with irradiated tumor as the only site of evaluable disease will not be eligible for protocol therapy unless there is documented disease progression within the previously radiated site.
  16. Patients must have recovered to grade </= 1 from all acute toxicity of previous radiation or hormonal therapy.
  17. Adequate hematologic and hepatic function: Granulocyte count >/= 1,500/mcL, Platelet count >/= 100,000/mcL, Bilirubin </= 1.5 x ULN, AST and/or ALT </= 2 x ULN, Alkaline phosphatase (liver component, if fractionated) </= 2 x ULN, Serum Na, K+, Mg2+, Phosphate and Ca2+>/= Lower Limit of Normal (LLN) [subjects with low electrolyte levels must be repleted to normal for protocol entry]
  18. Patients must not receive any concurrent bisphosphonate therapy other than that prescribed by the study.
  19. Sexually active patients with reproductive potential must agree to use an effective method of birth control during the course of the study and for no less than 4 weeks after discontinuing study drug. Contraceptives must be used in a manner such that risk of failure is minimized. Oral contraceptives should be avoided in women with estrogen or progesterone receptor positive breast cancer.
  20. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
  21. All WOCBP MUST have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study.
  22. Patients with disease progression while receiving previous therapy in combination with bisphosphonates (including zoledronic acid) will be considered eligible for protocol participation.

Exclusion Criteria:

  1. Any malignancy (other than breast cancer) that required radiotherapy or systemic treatment within the past 5 years.
  2. 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)
  3. 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
  4. 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
  5. Concomitant Medications, consider the following prohibitions (Drugs must be discontinued for 7 days prior to starting protocol therapy):
  6. 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
  7. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
  8. Untreated or uncontrolled brain metastasis
  9. Patient inability to take or absorb oral medications
  10. 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
  11. Recent (within 8 weeks) or planned dental or jaw surgery (e.g., extraction, implants)
  12. Diagnosis of metabolic bone disease other than osteoporosis (e.g., Paget's disease of bone)
  13. Known hypersensitivity to zoledronic acid or aspirin
  14. Corrected serum calcium < 8.0 mg/dL (2.0 mmol/L) or >/= 12.0 mg/dL (3.0 mmol/L) at Visit 1. The formula to be used is: Corrected serum calcium (mg/dL) = Patient's serum calcium (mg/dL) + [0.8 x Midrange Albumin (g/dL) - Patient's Albumin (g/dL)]. 4.0g/dL to be used for the Midrange Albumin
  15. Serum creatinine greater than or equal to 1.5 times the institutional upper limits of normal or a creatinine clearance of <40 ml/min when calculated by the Cockcroft and Gault formula (see protocol text for formula)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00566618

United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27708
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Principal Investigator: Stacy Moulder, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00566618     History of Changes
Other Study ID Numbers: 2006-0900
NCI-2010-01575 ( Registry Identifier: NCI CTRP )
Study First Received: November 29, 2007
Last Updated: December 8, 2016

Keywords provided by M.D. Anderson Cancer Center:
Breast Cancer
Bone Metastases
Breast Cancer with Bone Metastases
Breast Cancer with Metastases to Bone
Zoledronic Acid

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Bone Neoplasms
Bone Marrow Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Zoledronic acid
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Physiological Effects of Drugs processed this record on May 23, 2017