Clinical trial NCT00410813: S0622, Dasatinib in Treating Patients With Stage IV Breast Cancer That Has Spread to the Bone
Official title: Phase II Studies of Two Different Schedules of Dasatinib (NSC-732517) in Bone Metastasis Predominant Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Cancer
Keywords: stage IV breast cancer
male breast cancer
recurrent breast cancer
bone metastases
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-12-13
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression-free Survival
timeFrame: Up to 2 years
Secondary outcomes:
measure: Response Rate (Complete and Partial, Confirmed and Unconfirmed)
timeFrame: Up to 2 years
measure: MUC-1 Antigen Response
timeFrame: at 4, 8, 16, and 24 weeks
measure: Circulating Tumor Cells (CTC) Response Rate
timeFrame: Up to 4 weeks
measure: Change in Serum Bone Turnover Markers Over Time -- NTx
timeFrame: at baseline, 4, and 8 weeks
measure: Change in Serum Bone Turnover Markers Over Time -- BAP
timeFrame: at baseline, 4, and 8 weeks
measure: Change in Serum Bone Turnover Markers Over Time
timeFrame: at baseline, 4, and 8 weeks
measure: Change in Serum Bone Turnover Markers Over Time -- OC
timeFrame: at baseline, 4, and 8 weeks
measure: Change in Serum Bone Turnover Markers Over Time -- OPG
timeFrame: at baseline, 4, and 8 weeks
measure: Change in Serum Bone Turnover Markers Over Time -- TRAP
timeFrame: at baseline, 4, and 8 weeks
measure: Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
timeFrame: Up to 2 years
measure: Mean Patient-reported Pain
timeFrame: Baseline, 8, 16, and 24 weeks
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Providence Cancer Center at Providence Hospital
state: Alabama
city: Anchorage
country: United States
facility: Alaska Regional Hospital Cancer Center
state: Alaska
city: Anchorage
country: United States
facility: Providence Cancer Center
state: Alaska
city: Bentonville
country: United States
facility: Highlands Oncology Group - Springdale
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants - Castro Valley
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Marysville
country: United States
facility: Tibotec Therapeutics - Division of Ortho Biotech Products, LP
state: California
city: Mountain View
country: United States
facility: El Camino Hospital Cancer Center
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Breast Surgeons, Incorporated
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Larry G Strieff MD Medical Corporation
state: California
city: Oakland
country: United States
facility: Tom K Lee, Incorporated
state: California
city: Pleasanton
country: United States
facility: Valley Care Medical Center
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants - Pleasanton
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center - San Pablo Campus
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Hartford
country: United States
facility: Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
state: Connecticut
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Valdosta
country: United States
facility: Pearlman Comprehensive Cancer Center at South Georgia Medical Center
state: Georgia
city: Decatur
country: United States
facility: Cancer Care Center of Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Davenport
country: United States
facility: Genesis Regional Cancer Center at Genesis Medical Center
state: Iowa
city: Davenport
country: United States
facility: Genesis Medical Center - West Campus
state: Iowa
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Albuquerque
country: United States
facility: Lovelace Medical Center - Downtown
state: New Mexico
city: Albuquerque
country: United States
facility: Hematology Oncology Associates, PC
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Rochester
country: United States
facility: Interlakes Oncology/Hematology PC
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Bellefontaine
country: United States
facility: Mary Rutan Hospital
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Grant Medical Center Cancer Care
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health - West Hospital
state: Ohio
city: Columbus
country: United States
facility: Doctors Hospital at Ohio Health
state: Ohio
city: Delaware
country: United States
facility: Grady Memorial Hospital
state: Ohio
city: Lancaster
country: United States
facility: Fairfield Medical Center
state: Ohio
city: Marietta
country: United States
facility: Strecker Cancer Center at Marietta Memorial Hospital
state: Ohio
city: Mount Vernon
country: United States
facility: Knox Community Hospital
state: Ohio
city: Newark
country: United States
facility: Licking Memorial Cancer Care Program at Licking Memorial Hospital
state: Ohio
city: Springfield
country: United States
facility: Community Hospital of Springfield and Clark County
state: Ohio
city: Westerville
country: United States
facility: Mount Carmel St. Ann's Cancer Center
state: Ohio
city: Zanesville
country: United States
facility: Genesis - Good Samaritan Hospital
state: Ohio
city: Salem
country: United States
facility: Salem Hospital Regional Cancer Care Services
state: Oregon
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Martinsville
country: United States
facility: Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
state: Virginia
city: Norton
country: United States
facility: Southwest Virginia Regional Cancer Center at Wellmonth Health
state: Virginia
city: Centralia
country: United States
facility: Providence Centralia Hospital
state: Washington
city: Federal Way
country: United States
facility: St. Francis Hospital
state: Washington
city: Olympia
country: United States
facility: Providence St. Peter Hospital Regional Cancer Center
state: Washington
city: Puyallup
country: United States
facility: Good Samaritan Cancer Center
state: Washington
city: Tacoma
country: United States
facility: Franciscan Cancer Center at St. Joseph Medical Center
state: Washington
city: Tacoma
country: United States
facility: Allenmore Hospital
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center at Tacoma General Hospital
state: Washington
city: Tacoma
country: United States
facility: St. Clare Hospital
state: Washington
city: Casper
country: United States
facility: Rocky Mountain Oncology
state: Wyoming
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Anne F. Schott, MD
role: STUDY_CHAIR
affiliation: University of Michigan Rogel Cancer Center
name: Catherine Van Poznak, MD
role: STUDY_CHAIR
References: