S0622, Dasatinib in Treating Patients With Stage IV Breast Cancer That Has Spread to the Bone

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00410813
First received: December 11, 2006
Last updated: May 22, 2013
Last verified: May 2013
  Purpose

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This randomized phase II trial is studying two different schedules of dasatinib to compare how well they work in treating patients with stage IV breast cancer that has spread to the bone.


Condition Intervention Phase
Breast Cancer
Metastatic Cancer
Drug: dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Studies of Two Different Schedules of Dasatinib (NSC-732517) in Bone Metastasis Predominant Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Progression-free survival, with disease progression defined as an increase in measurable disease, the appearance of new lesions, and/or clinical deterioration related to disease progression [ Time Frame: Disease assessed every 8 weeks for up to 2 years until progression. ] [ Designated as safety issue: No ]
    Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at last date of contact.


Secondary Outcome Measures:
  • MUC-1 antigen response [ Time Frame: at 4, 8, 16, and 24 weeks ] [ Designated as safety issue: No ]
    MUC-1 Complete Response is reduction in MUC-1 such that MUC-1 ≤ ULN. MUC-1 Partial Response is greater than or equal to a 50% reduction in MUC-1 from baseline, but not qualifying as a CR. MUC-1 Progression is greater than or equal to a 50% increase in MUC-1 from baseline. MUC-1 Stable Disease is MUC-1 response not qualifying as CR, PR, or Progression. MUC-1 Inadequate Assessment, response unknown: MUC-1 response has not been adequately assessed.

  • Change in serum bone turnover markers over time [ Time Frame: at 4, 8, 16, and 24 weeks ] [ Designated as safety issue: No ]
  • Circulating tumor cell (CTC) response [ Time Frame: at 4, 8, 16, and 24 weeks ] [ Designated as safety issue: No ]
    CTC Response: CTC < 5 cells / 7.5 mL; CTC Non-Response: CTC ≥ 5 cells / 7.5 mL; CTC Inadequate Assessment, response: CTC not able to be evaluated.

  • Toxicity [ Time Frame: Patients assessed at least every eight weeks while on protocol treatment, for up to 2 years ] [ Designated as safety issue: Yes ]
    Only adverse events that are possibly, probably or definitely related to study drug are reported.

  • Response rate (complete and partial, confirmed and unconfirmed) [ Time Frame: Patients assessed at least every eight weeks while on protocol treatment, for up to 2 years ] [ Designated as safety issue: No ]
    Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

  • Change in patient-reported pain [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
    "worst pain" score from the Brief Pain Inventory Short Form


Estimated Enrollment: 80
Study Start Date: March 2007
Estimated Study Completion Date: September 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral dasatinib once daily.
Drug: dasatinib
given orally
Experimental: Arm II
Patients receive oral dasatinib twice daily.
Drug: dasatinib
given orally

Detailed Description:

OBJECTIVES:

  • Compare the progression-free survival of patients with stage IV bone metastasis-predominant breast cancer treated with 1 of 2 treatment schedules of dasatinib.
  • Compare the response rate (complete and partial, confirmed and unconfirmed) in patients treated with these regimens.
  • Compare the MUC-1 antigen response rate (CA 15-3 or CA 27-29) in patients treated with these regimens.
  • Compare the circulating tumor cell response rate in patients treated with these regimens.
  • Compare the anti-osteoclast activity, as measured by changes in bone turnover markers, in patients treated with these regimens.
  • Compare the frequency and severity of toxicities of these regimens in these patients.
  • Compare the pain profiles of these patients and explore changes over time.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to concurrent trastuzumab (Herceptin®) treatment (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral dasatinib once daily.
  • Arm II: Patients receive oral dasatinib twice daily. In both treatment arms, treatment continues for at least 24 weeks in the absence of disease progression or unacceptable toxicity.

Blood samples are acquired from patients once weekly in weeks 1, 4, 8, 16, and 24. Samples are analyzed for tumor markers, circulating tumor cells, and bone markers.

Patients complete a self-reported brief pain inventory questionnaire at baseline and once in weeks 8, 16, and 24.

After completion of study treatment, patients are followed every 3-6 months for up to 2 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of breast carcinoma meeting the following criteria:

    • Stage IV disease
    • Bone metastasis-predominant disease, defined as the presence of ≥ 1 bone metastasis with or without nonbone (visceral or soft tissue) disease where the number of bone metastases is at least the number of measurable visceral target lesions

      • Visceral disease that does not cause a reduction in ECOG performance status allowed
  • Must meet 1 of the following criteria:

    • Measurable disease within the past 28 days
    • Nonmeasurable disease with rising serum CA 15-3, CA 27-29, CEA, or CA-125 documented by 2 consecutive measurements taken ≥ 14 days apart with the most recent measurement being within the past 42 days

      • These measurements need not be consecutive, and the prior measurement could have been months to years prior to the current measurement if the marker is considered by the investigator to reflect disease progression
      • The second serum marker value must be greater than the institution's upper limit of normal and show ≥ a 20% increase over the first measurement
  • No symptomatic brain or CNS metastases

    • Prior CNS or brain metastasis allowed provided it was treated with radiotherapy ≥ 8 weeks ago
  • No pleural or pericardial effusion
  • Hormone receptor status known

    • Estrogen receptor- and/or progesterone receptor-positive disease must have progressed on ≥ 1 hormonal therapy in the metastatic setting

PATIENT CHARACTERISTICS:

  • Male or female
  • Menopausal status not specified
  • Zubrod performance status 0-2
  • QTc < 450 msec by EKG
  • Ejection fraction ≥ 50% by MUGA or 2-dimensional echocardiogram with no significant abnormalities within the past 12 weeks for patients on trastuzumab
  • No active infection requiring systemic therapy
  • No uncontrolled concurrent condition that would preclude the ability to take oral medication, including the following:

    • Nausea
    • Vomiting
    • Diarrhea
    • Lack of physical integrity of the upper gastrointestinal tract
    • Malabsorption syndrome
  • No clinically significant cardiac disease, including the following:

    • Congestive heart failure
    • Symptomatic coronary artery disease
    • Cardiac arrhythmias not well controlled
    • Myocardial infarction within the past 12 months
  • No concurrent active malignancy

    • Prior malignancies allowed provided the patient is currently disease-free
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 3 months after completion of study therapy

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior RankL inhibitor therapy
  • No more than 1 prior cytotoxic chemotherapy for metastatic disease
  • At least 3 weeks since prior chemotherapy and recovered
  • At least 1 week since prior radiotherapy to non-CNS disease and recovered
  • At least 3 weeks since prior and no concurrent intravenous bisphosphates (e.g., zoledronate)
  • At least 7 days since prior and no concurrent antiplatelet agents, including any of the following*:

    • Anticoagulants (e.g., tirofiban, eptifibatide, ticlopidine)
    • Aspirin or aspirin-containing combinations
    • Dipyridamole
    • Epoprostenol
    • Clopidogrel
    • Cilostazol
    • Abciximab NOTE: *Nonsteroidal anti-inflammatory drugs and medically indicated platelet-inhibiting medication allowed
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

    • HIV protease inhibitors (e.g., amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir)
    • Select antibiotics (e.g., ciprofloxacin, clarithromycin, doxycycline, enoxacin, isoniazid, telithromycin)
    • Azole antifungals (e.g., itraconazole, ketoconazole, miconazole, voriconazole)
    • Select anesthetics (e.g., ketamine, propofol)
    • Hypericum perforatum (St. John's wort)
    • Nefazodone
    • Nicardipine
    • Diclofenac
    • Quinidine
    • Imatinib mesylate
  • At least 7 days since prior and no concurrent medications that prolong the QTc interval, including any of the following:

    • Antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide phosphate, amiodarone, sotalol hydrochloride, ibutilide, dofetilide)
    • Antipsychotic agents (e.g., chlorpromazine, mesoridazine, thioridazine, pimozide, haloperidol, droperidol)
    • Select antibiotics (e.g., erythromycin, clarithromycin, sparfloxacin, pentamidine)
    • Narcotic analgesics (e.g., levomethadyl, methadone, domperidone)
    • Calcium channel blockers (e.g., bepridil, lidoflazine)
    • Antimalarial agents (e.g., halofantrine, chloroquine)
    • Parasympathomimetic agents (e.g., cisapride)
    • Arsenic trioxide
  • No other concurrent antineoplastic therapy for breast cancer, including any of the following:

    • Radiotherapy
    • Chemotherapy
    • Immunotherapy
    • Biologic therapy
    • Hormonal therapy
    • Gene therapy
  • No concurrent grapefruit juice consumption
  • No concurrent short-acting antacid agents within 2 hours of dasatinib administration
  • Concurrent trastuzumab (Herceptin®) therapy for HER-2 positive patients allowed provided patients have been on continuous trastuzumab for ≥ 12 weeks
  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 ClinicalTrials.gov identifier: NCT00410813

  Show 117 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Anne F. Schott, MD University of Michigan Cancer Center
Study Chair: Catherine Van Poznak, MD University of Michigan Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00410813     History of Changes
Other Study ID Numbers: CDR0000520348, S0622, U10CA032102
Study First Received: December 11, 2006
Last Updated: May 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
stage IV breast cancer
male breast cancer
recurrent breast cancer
bone metastases

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014