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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00410813
• Other study ID #: CDR0000520348
• Secondary ID: S0622U10CA032102
• Status: Active, not recruiting
• Phase: Phase 2
• First received: December 11, 2006
• Last updated: May 22, 2013
• Start date: March 2007
• Est. completion date: September 2013

Study information

• Verified date: May 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: September 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Drug:
• dasatinib
given orally

Locations

Country	Name	City	State
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Hematology Oncology Associates, PC	Albuquerque	New Mexico
United States	Lovelace Medical Center - Downtown	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Alaska Regional Hospital Cancer Center	Anchorage	Alaska
United States	Providence Cancer Center	Anchorage	Alaska
United States	AnMed Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	Highlands Oncology Group - Springdale	Bentonville	Arkansas
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California
United States	Providence Centralia Hospital	Centralia	Washington
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Crossroads Cancer Center	Effingham	Illinois
United States	St. Francis Hospital	Federal Way	Washington
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Valley Medical Oncology	Fremont	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Foote Memorial Hospital	Jackson	Michigan
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia
United States	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Providence Cancer Center at Providence Hospital	Mobile	Alabama
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	El Camino Hospital Cancer Center	Mountain View	California
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Breast Surgeons, Incorporated	Oakland	California
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee, Incorporated	Oakland	California
United States	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington
United States	Valley Care Medical Center	Pleasanton	California
United States	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Good Samaritan Cancer Center	Puyallup	Washington
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Salem Hospital Regional Cancer Care Services	Salem	Oregon
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Doctors Medical Center - San Pablo Campus	San Pablo	California
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Allenmore Hospital	Tacoma	Washington
United States	CCOP - Northwest	Tacoma	Washington
United States	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington
United States	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington
United States	St. Clare Hospital	Tacoma	Washington
United States	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia
United States	St. John Macomb Hospital	Warren	Michigan
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 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.	Disease assessed every 8 weeks for up to 2 years until progression.	No
Secondary	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. MUC-1 Inadequate Assessment, response unknown: MUC-1 response has not been adequately assessed.	at 4, 8, 16, and 24 weeks	No
Secondary	Change in serum bone turnover markers over time		at 4, 8, 16, and 24 weeks	No
Secondary	Circulating tumor cell (CTC) response	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.	at 4, 8, 16, and 24 weeks	No
Secondary	Toxicity	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Patients assessed at least every eight weeks while on protocol treatment, for up to 2 years	Yes
Secondary	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 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.	Patients assessed at least every eight weeks while on protocol treatment, for up to 2 years	No
Secondary	Change in patient-reported pain	"worst pain" score from the Brief Pain Inventory Short Form	baseline and 24 weeks	No