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

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00410813
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 85
• Locations: 117
• Arms: 2
• Duration (Months): 82.1
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Metastatic Cancer	Drug: dasatinib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Up to 2 years]

   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.

Secondary Outcome Measures

1. Response Rate (Complete and Partial, Confirmed and Unconfirmed) [Up to 2 years]

   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.

2. MUC-1 Antigen Response [at 4, 8, 16, and 24 weeks]

   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.

3. Circulating Tumor Cells (CTC) Response Rate [Up to 4 weeks]

   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.

4. Change in Serum Bone Turnover Markers Over Time -- NTx [at baseline, 4, and 8 weeks]

   Analysis included mean values of the serum biomarker NTx at baseline, 4, and 8 weeks.

5. Change in Serum Bone Turnover Markers Over Time -- BAP [at baseline, 4, and 8 weeks]

   Analysis included mean values of the serum biomarker BAP at baseline, 4, and 8 weeks.

6. Change in Serum Bone Turnover Markers Over Time [at baseline, 4, and 8 weeks]

   Analysis included mean values of the serum biomarkers sRANKL, IL-6, DKK, VEGF at baseline, 4, and 8 weeks.

7. Change in Serum Bone Turnover Markers Over Time -- OC [at baseline, 4, and 8 weeks]

   Analysis included mean values of the serum biomarker OC at baseline, 4, and 8 weeks.

8. Change in Serum Bone Turnover Markers Over Time -- OPG [at baseline, 4, and 8 weeks]

   Analysis included mean values of the serum biomarker OPG at baseline, 4, and 8 weeks.

9. Change in Serum Bone Turnover Markers Over Time -- TRAP [at baseline, 4, and 8 weeks]

   Analysis included mean values of the serum biomarker TRAP at baseline, 4, and 8 weeks.

10. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [Up to 2 years]

    Only adverse events that are possibly, probably or definitely related to study drug are reported.

11. Mean Patient-reported Pain [Baseline, 8, 16, and 24 weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Providence Cancer Center at Providence Hospital	Mobile	Alabama	United States	36608
2	Alaska Regional Hospital Cancer Center	Anchorage	Alaska	United States	99508
3	Providence Cancer Center	Anchorage	Alaska	United States	99508
4	Highlands Oncology Group - Springdale	Bentonville	Arkansas	United States	72712
5	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
6	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
7	Eden Medical Center	Castro Valley	California	United States	94546
8	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California	United States	94546
9	Valley Medical Oncology	Fremont	California	United States	94538
10	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
11	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California	United States	95901
12	El Camino Hospital Cancer Center	Mountain View	California	United States	94040
13	Highland General Hospital	Oakland	California	United States	94602
14	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
15	Bay Area Breast Surgeons, Incorporated	Oakland	California	United States	94609
16	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
17	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
18	Tom K Lee, Incorporated	Oakland	California	United States	94609
19	Valley Care Medical Center	Pleasanton	California	United States	94588
20	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California	United States	94588
21	University of California Davis Cancer Center	Sacramento	California	United States	95817
22	Doctors Medical Center - San Pablo Campus	San Pablo	California	United States	94806
23	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado	United States	80045
24	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
25	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
26	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia	United States	31603
27	Cancer Care Center of Decatur	Decatur	Illinois	United States	62526
28	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
29	Crossroads Cancer Center	Effingham	Illinois	United States	62401
30	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
31	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
32	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
33	Genesis Medical Center - West Campus	Davenport	Iowa	United States	52804
34	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
35	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118
36	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
37	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
38	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
39	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
40	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
41	Hurley Medical Center	Flint	Michigan	United States	48503
42	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
43	Foote Memorial Hospital	Jackson	Michigan	United States	49201
44	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
45	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
46	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
47	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
48	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
49	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
50	St. John Macomb Hospital	Warren	Michigan	United States	48093
51	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216
52	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
53	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
54	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
55	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
56	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
57	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
58	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
59	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
60	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
61	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
62		Great Falls	Montana	United States	59405
63	Northern Montana Hospital	Havre	Montana	United States	59501
64	St. Peter's Hospital	Helena	Montana	United States	59601
65	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
66	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
67	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
68	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
69	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
70	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
71	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
72	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
73	Lovelace Medical Center - Downtown	Albuquerque	New Mexico	United States	87102
74	Hematology Oncology Associates, PC	Albuquerque	New Mexico	United States	87106
75	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
76	Interlakes Oncology/Hematology PC	Rochester	New York	United States	14623
77	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
78	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
79	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
80	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
81	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
82	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
83	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
84	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
85	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
86	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
87	CCOP - Columbus	Columbus	Ohio	United States	43215
88	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
89	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
90	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
91	Grady Memorial Hospital	Delaware	Ohio	United States	43015
92	Fairfield Medical Center	Lancaster	Ohio	United States	43130
93	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
94	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
95	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
96	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
97	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
98	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
99	Salem Hospital Regional Cancer Care Services	Salem	Oregon	United States	97309-5014
100	AnMed Cancer Center	Anderson	South Carolina	United States	29621
101	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
102	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
103	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
104	Danville Regional Medical Center	Danville	Virginia	United States	24541
105	Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia	United States	24115
106	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia	United States	24273
107	Providence Centralia Hospital	Centralia	Washington	United States	98531-9027
108	St. Francis Hospital	Federal Way	Washington	United States	98003
109	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington	United States	98506-5166
110	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
111	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
112	Allenmore Hospital	Tacoma	Washington	United States	98405
113	CCOP - Northwest	Tacoma	Washington	United States	98405
114	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
115	St. Clare Hospital	Tacoma	Washington	United States	98499
116	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
117	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Anne F. Schott, MD, University of Michigan Rogel Cancer Center
• Study Chair: Catherine Van Poznak, MD, University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00410813
• Other Study ID Numbers: CDR0000520348; S0622; U10CA032102
• First Posted: Dec 13, 2006
• Last Update Posted: Jul 2, 2017
• Last Verified: May 1, 2017

• Keywords provided by Southwest Oncology Group: stage IV breast cancer; male breast cancer; recurrent breast cancer; bone metastases
• Additional relevant MeSH terms: Breast Neoplasms; Dasatinib

Study Results

Participant Flow

Arm/Group Title	Dasatinib, 100 mg, Daily	Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Dasatinib, 100 mg PO daily until progression of disease	Dasatinib, 70 mg PO twice daily until progression of disease
Period Title: Overall Study
STARTED	43	42
Eligible	41	38
COMPLETED	0	0
NOT COMPLETED	43	42

Baseline Characteristics

Arm/Group Title	Dasatinib, 100 mg, Daily	Dasatinib, 70 mg, Twice Daily	Total
Arm/Group Description	Dasatinib, 100 mg PO daily until progression of disease	Dasatinib, 70 mg PO twice daily until progression of disease	Total of all reporting groups
Overall Participants	41	38	79
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	65	60
Sex: Female, Male (Count of Participants)
Female	41 100%	38 100%	79 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 5.3%	2 2.5%
Not Hispanic or Latino	36 87.8%	34 89.5%	70 88.6%
Unknown or Not Reported	5 12.2%	2 5.3%	7 8.9%
Race/Ethnicity, Customized (participants) [Number]
White	38 92.7%	35 92.1%	73 92.4%
Black	1 2.4%	2 5.3%	3 3.8%
Pacific Islander	1 2.4%	0 0%	1 1.3%
Native American	1 2.4%	0 0%	1 1.3%
Asian	0 0%	1 2.6%	1 1.3%
Use of trastuzumab at time of registration (participants) [Number]
Yes	1 2.4%	0 0%	1 1.3%
No	40 97.6%	38 100%	78 98.7%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All eligible patients were included in this analysis.

Arm/Group Title	Dasatinib, 100 mg, Daily	Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Dasatinib, 100 mg PO daily until progression of disease	Dasatinib, 70 mg PO twice daily until progression of disease
Measure Participants	41	38
Median (95% Confidence Interval) [weeks]	10.3	15.3

2. Secondary Outcome

Title	Response Rate (Complete and Partial, Confirmed and Unconfirmed)
Description	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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All eligible patients

Arm/Group Title	Dasatinib, 100 mg, Daily	Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Dasatinib, 100 mg PO daily until progression of disease	Dasatinib, 70 mg PO twice daily until progression of disease
Measure Participants	41	38
Partial Response	1 2.4%	0 0%
Stable/No Response	14 34.1%	18 47.4%
Increasing Disease	20 48.8%	10 26.3%
Assessment Inadequate	6 14.6%	10 26.3%

3. Secondary Outcome

Title	MUC-1 Antigen Response
Description	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.
Time Frame	at 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

MUC-1 Inadequate Assessment, response unknown: MUC-1 response has not been adequately assessed at indicated timepoints.

Arm/Group Title	Dasatinib, 100 mg, Daily	Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Dasatinib, 100 mg PO daily until progression of disease	Dasatinib, 70 mg PO twice daily until progression of disease
Measure Participants	0	0

4. Secondary Outcome

Title	Circulating Tumor Cells (CTC) Response Rate
Description	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.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Treatment arms are combined in this analysis. Only eligible patients evaluated at both baseline and at 4 weeks were included. Patients analyzed for CTC response only includes patients who had elevated CTCs at baseline.

Arm/Group Title	Dasatinib
Arm/Group Description	Patients received either Arm 1: Dasatinib, 100 mg, daily or Arm 2: Dasatinib, 70 mg, twice daily.
Measure Participants	16
Number [participants]	4 9.8%

5. Secondary Outcome

Title	Change in Serum Bone Turnover Markers Over Time -- NTx
Description	Analysis included mean values of the serum biomarker NTx at baseline, 4, and 8 weeks.
Time Frame	at baseline, 4, and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of patients with samples to analyze: baseline n=66, 4 weeks n=54, 8 weeks n=52.

Arm/Group Title	NTx at Baseline	NTx at 4 Weeks	NTx at 8 Weeks
Arm/Group Description
Measure Participants	66	54	52
Mean (Standard Deviation) [nM BCE]	21.84 (12.32)	19.23 (11.32)	12.88 (13.09)

6. Secondary Outcome

Title	Change in Serum Bone Turnover Markers Over Time -- BAP
Description	Analysis included mean values of the serum biomarker BAP at baseline, 4, and 8 weeks.
Time Frame	at baseline, 4, and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of patients with samples to analyze: baseline n=66, 4 weeks n=54, 8 weeks n=52.

Arm/Group Title	BAP at Baseline	BAP at 4 Weeks	BAP at 8 Weeks
Arm/Group Description
Measure Participants	66	54	52
Mean (Standard Deviation) [ug/L]	24.07 (15.95)	24.35 (13.94)	25.61 (14.05)

7. Secondary Outcome

Title	Change in Serum Bone Turnover Markers Over Time
Description	Analysis included mean values of the serum biomarkers sRANKL, IL-6, DKK, VEGF at baseline, 4, and 8 weeks.
Time Frame	at baseline, 4, and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of patients with samples to analyze: baseline n=66, 4 weeks n=54, 8 weeks n=52.

Arm/Group Title	Serum Biomarker at Baseline	Serum Biomarker at 4 Weeks	Serum Biomarker at 8 Weeks
Arm/Group Description
Measure Participants	66	54	52
DKK	1157.64 (1465.83)	1470.50 (1985.09)	1575.05 (1993.44)
IL-6	250.17 (1588.17)	19.03 (73.70)	32.03 (190.36)
VEGF	459.01 (324.89)	424.21 (355.33)	412.33 (346.58)
sRANKL	772172 (1580514)	531173 (910765)	553459 (864151)

8. Secondary Outcome

Title	Change in Serum Bone Turnover Markers Over Time -- OC
Description	Analysis included mean values of the serum biomarker OC at baseline, 4, and 8 weeks.
Time Frame	at baseline, 4, and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of patients with samples to analyze: baseline n=66, 4 weeks n=54, 8 weeks n=52.

Arm/Group Title	OC at Baseline	OC at 4 Weeks	OC at 8 Weeks
Arm/Group Description
Measure Participants	66	54	52
Mean (Standard Deviation) [ng/mL]	11.08 (7.76)	13.10 (9.17)	13.54 (10.20)

9. Secondary Outcome

Title	Change in Serum Bone Turnover Markers Over Time -- OPG
Description	Analysis included mean values of the serum biomarker OPG at baseline, 4, and 8 weeks.
Time Frame	at baseline, 4, and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of patients with samples to analyze: baseline n=66, 4 weeks n=54, 8 weeks n=52.

Arm/Group Title	OPG at Baseline	OPG at 4 Weeks	OPG at 8 Weeks
Arm/Group Description
Measure Participants	66	54	52
Mean (Standard Deviation) [pmol/L]	4.56 (5.44)	6.53 (9.46)	6.71 (10.09)

10. Secondary Outcome

Title	Change in Serum Bone Turnover Markers Over Time -- TRAP
Description	Analysis included mean values of the serum biomarker TRAP at baseline, 4, and 8 weeks.
Time Frame	at baseline, 4, and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of patients with samples to analyze: baseline n=66, 4 weeks n=54, 8 weeks n=52.

Arm/Group Title	TRAP at Baseline	TRAP at 4 Weeks	TRAP at 8 Weeks
Arm/Group Description
Measure Participants	66	54	52
Mean (Standard Deviation) [U/L]	6.83 (6.42)	5.41 (4.23)	5.59 (4.40)

11. Secondary Outcome

Title	Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Description	Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any CTCAE v3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Arm/Group Title	Dasatinib, 100 mg, Daily	Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Dasatinib, 100 mg PO daily until progression of disease	Dasatinib, 70 mg PO twice daily until progression of disease
Measure Participants	41	38
ALT, SGPT (serum glutamic pyruvic transaminase)	1 2.4%	2 5.3%
AST, SGOT	1 2.4%	1 2.6%
Albumin, serum-low (hypoalbuminemia)	0 0%	1 2.6%
Anorexia	0 0%	1 2.6%
Dehydration	0 0%	1 2.6%
Diarrhea	0 0%	2 5.3%
Dyspnea (shortness of breath)	1 2.4%	4 10.5%
Fatigue (asthenia, lethargy, malaise)	0 0%	6 15.8%
Hemoglobin	0 0%	1 2.6%
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	0 0%	1 2.6%
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	1 2.4%	1 2.6%
Infection with unknown ANC - Dental-tooth	1 2.4%	0 0%
Left ventricular systolic dysfunction	2 4.9%	1 2.6%
Lymphopenia	0 0%	1 2.6%
Nausea	0 0%	1 2.6%
Neutrophils/granulocytes (ANC/AGC)	0 0%	1 2.6%
Pain - Bone	1 2.4%	1 2.6%
Pain - Buttock	1 2.4%	0 0%
Pain - Chest wall	1 2.4%	0 0%
Pain - Chest/thorax NOS	1 2.4%	0 0%
Pain - Head/headache	1 2.4%	1 2.6%
Platelets	2 4.9%	1 2.6%
Pleural effusion (non-malignant)	1 2.4%	2 5.3%
Pneumonitis/pulmonary infiltrates	1 2.4%	0 0%
Potassium, serum-low (hypokalemia)	1 2.4%	3 7.9%
Pulmonary hypertension	0 0%	1 2.6%
Pulmonary/Upper Respiratory-Other (Specify)	0 0%	1 2.6%
Rash/desquamation	0 0%	1 2.6%
Sodium, serum-low (hyponatremia)	0 0%	1 2.6%
Vomiting	0 0%	1 2.6%

12. Secondary Outcome

Title	Mean Patient-reported Pain
Description	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.
Time Frame	Baseline, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

All patients with non-missing values were analyzed

Arm/Group Title	Dasatinib - Baseline	Dasatinib - Week 8	Dasatinib - Week 16	Dasatinib - Week 24
Arm/Group Description	Patients received either Arm 1: Dasatinib, 100 mg, daily or Arm 2: Dasatinib, 70 mg, twice daily.	Patients received either Arm 1: Dasatinib, 100 mg, daily or Arm 2: Dasatinib, 70 mg, twice daily.	Patients received either Arm 1: Dasatinib, 100 mg, daily or Arm 2: Dasatinib, 70 mg, twice daily.	Patients received either Arm 1: Dasatinib, 100 mg, daily or Arm 2: Dasatinib, 70 mg, twice daily.
Measure Participants	79	68	37	41
Mean (Standard Deviation) [units on a scale]	3.37 (2.93)	3.82 (3.04)	3.06 (2.61)	3.73 (3.03)

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Dasatinib, 100 mg, Daily		Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Dasatinib, 100 mg PO daily until progression of disease		Dasatinib, 70 mg PO twice daily until progression of disease
All Cause Mortality
	Dasatinib, 100 mg, Daily		Dasatinib, 70 mg, Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dasatinib, 100 mg, Daily		Dasatinib, 70 mg, Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/41 (14.6%)		12/38 (31.6%)
Cardiac disorders
Left ventricular systolic dysfunction	0/41 (0%)		1/38 (2.6%)
Gastrointestinal disorders
Constipation	0/41 (0%)		1/38 (2.6%)
General disorders
Death not associated with CTCAE term - Death NOS	0/41 (0%)		1/38 (2.6%)
Sudden death	0/41 (0%)		1/38 (2.6%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	0/41 (0%)		1/38 (2.6%)
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	1/41 (2.4%)		1/38 (2.6%)
Injury, poisoning and procedural complications
Rash: dermatitis associated w/Chemoradiation	0/41 (0%)		1/38 (2.6%)
Metabolism and nutrition disorders
Anorexia	0/41 (0%)		1/38 (2.6%)
Potassium, serum-low (hypokalemia)	0/41 (0%)		1/38 (2.6%)
Musculoskeletal and connective tissue disorders
Pain - Back	0/41 (0%)		1/38 (2.6%)
Pain - Bone	1/41 (2.4%)		0/38 (0%)
Pain - Chest wall	1/41 (2.4%)		0/38 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS	1/41 (2.4%)		0/38 (0%)
Renal and urinary disorders
Renal failure	1/41 (2.4%)		0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	0/41 (0%)		1/38 (2.6%)
Pleural effusion (non-malignant)	1/41 (2.4%)		2/38 (5.3%)
Pneumonitis/pulmonary infiltrates	2/41 (4.9%)		0/38 (0%)
Pulmonary/Upper Respiratory-Other (Specify)	0/41 (0%)		1/38 (2.6%)
Vascular disorders
Thrombosis/thrombus/embolism	0/41 (0%)		1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Dasatinib, 100 mg, Daily		Dasatinib, 70 mg, Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/41 (82.9%)		36/38 (94.7%)
Blood and lymphatic system disorders
Hemoglobin	16/41 (39%)		22/38 (57.9%)
Gastrointestinal disorders
Constipation	8/41 (19.5%)		3/38 (7.9%)
Diarrhea	10/41 (24.4%)		14/38 (36.8%)
Dysphagia (difficulty swallowing)	1/41 (2.4%)		2/38 (5.3%)
Flatulence	3/41 (7.3%)		2/38 (5.3%)
Heartburn/dyspepsia	4/41 (9.8%)		1/38 (2.6%)
Nausea	15/41 (36.6%)		19/38 (50%)
Vomiting	10/41 (24.4%)		8/38 (21.1%)
General disorders
Edema: head and neck	1/41 (2.4%)		3/38 (7.9%)
Edema: limb	2/41 (4.9%)		6/38 (15.8%)
Fatigue (asthenia, lethargy, malaise)	19/41 (46.3%)		19/38 (50%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	3/41 (7.3%)		2/38 (5.3%)
Pain - Chest/thorax NOS	2/41 (4.9%)		2/38 (5.3%)
Pain-Other (Specify)	5/41 (12.2%)		5/38 (13.2%)
Rigors/chills	1/41 (2.4%)		2/38 (5.3%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	3/41 (7.3%)		0/38 (0%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	7/41 (17.1%)		12/38 (31.6%)
AST, SGOT	10/41 (24.4%)		16/38 (42.1%)
Alkaline phosphatase	6/41 (14.6%)		9/38 (23.7%)
Creatinine	5/41 (12.2%)		6/38 (15.8%)
Leukocytes (total WBC)	7/41 (17.1%)		7/38 (18.4%)
Lymphopenia	2/41 (4.9%)		3/38 (7.9%)
Metabolic/Laboratory-Other (Specify)	0/41 (0%)		2/38 (5.3%)
Neutrophils/granulocytes (ANC/AGC)	3/41 (7.3%)		4/38 (10.5%)
Platelets	4/41 (9.8%)		5/38 (13.2%)
Weight loss	2/41 (4.9%)		6/38 (15.8%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	0/41 (0%)		6/38 (15.8%)
Anorexia	8/41 (19.5%)		9/38 (23.7%)
Calcium, serum-low (hypocalcemia)	4/41 (9.8%)		7/38 (18.4%)
Dehydration	0/41 (0%)		2/38 (5.3%)
Glucose, serum-high (hyperglycemia)	11/41 (26.8%)		9/38 (23.7%)
Potassium, serum-low (hypokalemia)	4/41 (9.8%)		5/38 (13.2%)
Sodium, serum-low (hyponatremia)	4/41 (9.8%)		9/38 (23.7%)
Musculoskeletal and connective tissue disorders
Pain - Back	12/41 (29.3%)		4/38 (10.5%)
Pain - Bone	7/41 (17.1%)		10/38 (26.3%)
Pain - Extremity-limb	4/41 (9.8%)		4/38 (10.5%)
Pain - Joint	4/41 (9.8%)		3/38 (7.9%)
Pain - Muscle	3/41 (7.3%)		3/38 (7.9%)
Nervous system disorders
Dizziness	4/41 (9.8%)		1/38 (2.6%)
Neuropathy: sensory	6/41 (14.6%)		3/38 (7.9%)
Pain - Head/headache	11/41 (26.8%)		9/38 (23.7%)
Taste alteration (dysgeusia)	2/41 (4.9%)		4/38 (10.5%)
Tremor	0/41 (0%)		2/38 (5.3%)
Psychiatric disorders
Insomnia	7/41 (17.1%)		4/38 (10.5%)
Mood alteration - anxiety	6/41 (14.6%)		4/38 (10.5%)
Mood alteration - depression	3/41 (7.3%)		1/38 (2.6%)
Renal and urinary disorders
Urinary frequency/urgency	1/41 (2.4%)		2/38 (5.3%)
Urine color change	0/41 (0%)		2/38 (5.3%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/41 (7.3%)		1/38 (2.6%)
Cough	8/41 (19.5%)		8/38 (21.1%)
Dyspnea (shortness of breath)	7/41 (17.1%)		12/38 (31.6%)
Pleural effusion (non-malignant)	7/41 (17.1%)		3/38 (7.9%)
Skin and subcutaneous tissue disorders
Hair loss/Alopecia (scalp or body)	0/41 (0%)		2/38 (5.3%)
Nail changes	1/41 (2.4%)		2/38 (5.3%)
Pruritus/itching	0/41 (0%)		4/38 (10.5%)
Rash/desquamation	5/41 (12.2%)		6/38 (15.8%)
Rash: acne/acneiform	3/41 (7.3%)		6/38 (15.8%)
Vascular disorders
Hot flashes/flushes	3/41 (7.3%)		3/38 (7.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.