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

NCT00566618 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2006-0900NCI-2015-01920
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

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.

Conditions

Breast Cancer; Bone Metastases

Keywords

Breast Cancer; Bone Metastases; Breast Cancer with Bone Metastases; Breast Cancer with Metastases to Bone; Dasatinib; Zometa; Zoledronic Acid; Zoledronate; BMS-345825; Sprycel®

Outcome Measures

Primary Outcomes (2)

• Objective Response in Bone From Time of Initiation of Therapy to > 6 Months

  Objective response rate is defined as the clinical benefit rate (complete and partial response) + stable disease \> 6 months in bone.

  6 months

• Phase I - Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) for Dasatinib in Combination With Zoledronic Acid

  To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) for dasatinib in combination with zoledronic acid.

  day 1 (+/- 48 hours) prior to therapy during cycle 2 and all subsequent cycles

Study Arms (1)

Dasatinib + Zoledronic Acid

EXPERIMENTAL

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; Drug: Zoledronic Acid

Interventions

Dasatinib DRUG

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.

Also known as: BMS-345825, Sprycel®

Dasatinib + Zoledronic Acid

Zoledronic Acid DRUG

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.

Also known as: Zoledronate, Zometa®

Dasatinib + Zoledronic Acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \</= 2.
• Patients must not require concurrent radiation or chemotherapy while receiving protocol therapy.
• Patients must not have an active infection requiring the use of intravenous antibiotics. The use of oral antibiotics as prophylaxis is allowed.
• Patients must have a baseline ECG with QTc within the normal range within 28 days prior to registration.
• Patients must be informed of the investigational nature of the study and must sign and give written informed consent.
• 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.

You may not qualify if:

• 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
• Recent (within 8 weeks) or planned dental or jaw surgery (e.g., extraction, implants)
• Diagnosis of metabolic bone disease other than osteoporosis (e.g., Paget's disease of bone)
• Known hypersensitivity to zoledronic acid or aspirin
• 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
• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Dasatinib; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles

Results Point of Contact

• Title: Debu Tripathy, Chair, Breast Medical Oncology
• Organization: UT MD Anderson Cancer Center

dtripathy@mdanderson.org

(713) 792-2817

Study Officials

• Stacy Moulder, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2007
• First Posted: December 3, 2007
• Study Start: November 1, 2007
• Primary Completion: November 17, 2020
• Study Completion: November 17, 2020
• Last Updated: February 25, 2022
• Results First Posted: February 25, 2022

Record last verified: 2022-02

Locations

US (3)