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

Phase II Studies of Two Different Schedules of Dasatinib (NSC-732517) in Bone Metastasis Predominant Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: dasatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Providence Cancer Center at Providence Hospital
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Cancer Center
    • Anchorage, Alaska, United States, 99508
      • Alaska Regional Hospital Cancer Center
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Highlands Oncology Group - Springdale
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Eden Medical Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants - Castro Valley
    • Fremont, California, United States, 94538
      • Valley Medical Oncology
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Marysville, California, United States, 95901
      • Tibotec Therapeutics - Division of Ortho Biotech Products, LP
    • Mountain View, California, United States, 94040
      • El Camino Hospital Cancer Center
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Larry G Strieff MD Medical Corporation
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Bay Area Breast Surgeons, Incorporated
    • Oakland, California, United States, 94609
      • Tom K Lee, Incorporated
    • Pleasanton, California, United States, 94588
      • Valley Care Medical Center
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants - Pleasanton
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • San Pablo, California, United States, 94806
      • Doctors Medical Center - San Pablo Campus
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at UC Health Sciences Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Valdosta, Georgia, United States, 31603
      • Pearlman Comprehensive Cancer Center at South Georgia Medical Center
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Cancer Care Center of Decatur
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Iowa
    • Davenport, Iowa, United States, 52804
      • Genesis Medical Center - West Campus
    • Davenport, Iowa, United States, 52803
      • Genesis Regional Cancer Center at Genesis Medical Center
  • Kansas
    • Salina, Kansas, United States, 67401
      • Tammy Walker Cancer Center at Salina Regional Health Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Cancer Clinic
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
    • Great Falls, Montana, United States, 59405-5309
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates, PC
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center - Downtown
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14623
      • Interlakes Oncology/Hematology PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Hendersonville, North Carolina, United States, 28791
      • Pardee Memorial Hospital
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center Cancer Care
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Westerville, Ohio, United States, 43081
      • Mount Carmel St. Ann's Cancer Center
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • Oregon
    • Salem, Oregon, United States, 97309-5014
      • Salem Hospital Regional Cancer Care Services
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Cancer Center
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37662
      • Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Martinsville, Virginia, United States, 24115
      • Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
    • Norton, Virginia, United States, 24273
      • Southwest Virginia Regional Cancer Center at Wellmonth Health
  • Washington
    • Centralia, Washington, United States, 98531-9027
      • Providence Centralia Hospital
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Olympia, Washington, United States, 98506-5166
      • Providence St. Peter Hospital Regional Cancer Center
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Tacoma, Washington, United States, 98405-3004
      • Franciscan Cancer Center at St. Joseph Medical Center
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center at Tacoma General Hospital
    • Tacoma, Washington, United States, 98499
      • St. Clare Hospital
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	RECIST progression defined as 20% increase in the sum of longest diameters of target measurable lesions over the smallest sum observed, unequivocal progression of non-measurable disease, the appearance of any new lesion/site, death due to disease without prior documentation of progression and without symptomatic deterioration, development of one or more new bone lesions from baseline, or symptomatic deterioration related to disease progression. 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.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (Complete and Partial, Confirmed and Unconfirmed)	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, unequivocal progression of non-measurable disease, appearance of any new lesion/site, 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.	Up to 2 years
MUC-1 Antigen Response	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.	at 4, 8, 16, and 24 weeks
Circulating Tumor Cells (CTC) Response Rate	CTC response at 4 weeks is defined as the number of patients with initially elevated CTCs (>= 5 cells/7.5 ml), whose CTC level drops to < 5.	Up to 4 weeks
Change in Serum Bone Turnover Markers Over Time -- NTx	Analysis included mean values of the serum biomarker NTx at baseline, 4, and 8 weeks.	at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- BAP	Analysis included mean values of the serum biomarker BAP at baseline, 4, and 8 weeks.	at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time	Analysis included mean values of the serum biomarkers sRANKL, IL-6, DKK, VEGF at baseline, 4, and 8 weeks.	at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- OC	Analysis included mean values of the serum biomarker OC at baseline, 4, and 8 weeks.	at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- OPG	Analysis included mean values of the serum biomarker OPG at baseline, 4, and 8 weeks.	at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- TRAP	Analysis included mean values of the serum biomarker TRAP at baseline, 4, and 8 weeks.	at baseline, 4, and 8 weeks
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 2 years
Mean Patient-reported Pain	Patient's rating of "worst pain" experienced between prestudy and week 24. Changes of >=2 points on the Brief Pain Inventory (BPI) are of interest. Pain is self-reported on the Brief Pain Inventory Short Form, on a 0-10 response scale, with higher scores reflecting more pain and more interference with functioning.	Baseline, 8, 16, and 24 weeks

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Catherine Van Poznak, MD, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 11, 2006
• First Submitted That Met QC Criteria: December 11, 2006
• First Posted (Estimate): December 13, 2006

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: May 31, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; bone metastases; male breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: CDR0000520348; U10CA032102 (U.S. NIH Grant/Contract); S0622 (Other Identifier: SWOG)