S1501 Carvedilol in Preventing Cardiac Toxicity in Patients With Metastatic HER-2-Positive Breast Cancer



Status:Recruiting
Conditions:Breast Cancer, Brain Cancer, Cardiology
Therapuetic Areas:Cardiology / Vascular Diseases, Oncology
Healthy:No
Age Range:18 - Any
Updated:9/2/2018
Start Date:September 15, 2017
End Date:February 1, 2023

Use our guide to learn which trials are right for you!

Prospective Evaluation of Carvedilol in Prevention of Cardiac Toxicity in Patients With Metastatic HER-2+ Breast Cancer, Phase III

This phase III trial studies how well carvedilol works in preventing cardiac toxicity in
patients with human epidermal growth factor receptor (HER)-2-positive breast cancer that has
spread to other places in the body. A beta-blocker, such as carvedilol, is used to treat
heart failure and high blood pressure, and it may prevent the heart from side effects of
chemotherapy.

PRIMARY OBJECTIVES:

I. To assess whether prophylactic beta blocker therapy with carvedilol compared with no
intervention reduces the risk of subsequent cardiac dysfunction in patients with metastatic
breast cancer receiving trastuzumab?based HER-2 targeted therapy.

SECONDARY OBJECTIVES:

I. To assess whether prophylactic beta blocker therapy with carvedilol compared with no
intervention reduces the risk of predefined subsequent cardiac events in patients with
metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy.

II. To evaluate if prophylactic carvedilol compared with no intervention results in a longer
time to first interruption of trastuzumab?based HER-2 targeted therapy due to either cardiac
dysfunction or events.

III. To assess whether prophylactic beta blocker therapy with carvedilol compared with no
intervention reduces the risk of subsequent cardiac dysfunction OR events in this population.

IV. To establish and prospectively collect a predefined panel of baseline core cardiovascular
measures and develop a predictive model of cardiac dysfunction.

V. To evaluate the rate of cardiac dysfunction in an observational arm consisting of
individuals otherwise eligible for the study except for use of beta blockers, angiotensin
receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitors for other medical
reasons.

TERTIARY OBJECTIVES:

I. To evaluate the isoleucine (lle) 655 valine (Val) and and alanine (Ala)ll70 proline (Pro)
single nucleotide polymorphisms (SNPs) of the HER-2 gene as a predictive biomarker of
study-defined cardiac dysfunction.

II. To evaluate plasma neuregulin-1 at baseline and over study time as a predictive biomarker
of study-defined cardiac dysfunction.

III. To evaluate the feasibility of performing serial left ventricular strain in a National
Clinical Trials Network (NCTN) group setting, with the goal of 75% of patients contributing
both a baseline and at least one follow-up strain measurement.

IV. To bank blood for future translational medicine studies such as brain natriuretic peptide
(BNP), additional SNPs, and high sensitivity troponin.

OUTLINE: Patients are randomized to 1 of 2 arms. Patients taking beta blocker, ARB, or ACE
inhibitor at registration are assigned to Arm III.

ARM I: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive
carvedilol orally (PO) twice daily (BID). Courses repeat every 12 weeks for 108 weeks in the
absence of disease progression or unacceptable toxicity.

ARM II: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive no
study intervention for up to 108 weeks.

ARM III: Patients undergo observation for up to 108 weeks.

After completion of study, patients are followed up for up to 108 weeks.

Inclusion Criteria:

- STEP 1 REGISTRATION

- Patients must have metastatic breast cancer and be initiating within 7 days of step 1
registration or continuing trastuzumab?based HER-2 targeted therapy without concurrent
anthracyclines in first or second line setting; patients may have brain metastasis;
there is no limit for number of doses of HER-2 targeted therapy prior to registration;
examples of eligible HER-2 targeted therapy:

- Trastuzumab

- Trastuzumab + chemotherapy or hormonal therapy

- Trastuzumab + other HER-2 targeted agent with or without chemotherapy (such as
pertuzumab)

- Ado-trastuzumab (Kadcyla)

- NOTE: Patients on lapatinib without trastuzumab are not eligible; planned
treatment with concurrent HER-2 targeted therapy and anthracyclines is not
permitted

- Patients must be at increased risk for cardiotoxicity defined by at least one of the
following:

- Previous anthracycline exposure, OR

- 1 or more of the following risk factors for heart disease:

- Left ventricular ejection fraction (LVEF) 50-54% by local echocardiography
(ECHO) read

- Age >= 65

- Body mass index (BMI) >= 30 kg/m^2

- Current or prior anti-hypertensive therapy

- Diagnosis of coronary artery disease (CAD)

- Diabetes mellitus

- Atrial fibrillation/flutter

- Patients must not have taken within 21 days prior to step 1 registration, be currently
taking at the time of step 1 registration, or planning to take once registered to step
1 a beta blocker, ARB, or ACE inhibitor in order to be randomized (Arms 1 and 2)

- Patients currently taking a beta blocker, ARB, or ACE inhibitor at the time of
step 1 registration are eligible to register for the non-randomized observational
cohort (Arm 3)

- Patients must not be currently taking or planning to take during study treatment the
following medications:

- B2 agonists

- Bosutinib

- Ceritinib

- Floctafenine

- Methacholine

- Pazopanib

- Rivastigmine

- Vincristine

- Silodosin

- Patients must have a Zubrod Performance status of 0-2

- Patients must have a complete physical examination and medical history within 28 days
prior to registration

- Patients must have LVEF >= 50% by 2-dimensional (D) echocardiogram within 28 days
prior to registration; the echocardiogram must be obtained from a S1501 validated ECHO
laboratory (lab) and submitted for central review by the S1501 ECHO core lab; ECHO
should not be submitted for central read until patient has been otherwise deemed
eligible

- Serum bilirubin < 3.0 x institutional upper limit of normal (IULN)

- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and
serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) < 5.0 x IULN

- Patients must have electrocardiogram with corrected QT (QTc) with correction within 28
days prior to registration

- Patients must have a systolic blood pressure >= 80 mm Hg within 14 days prior to
registration

- Patients must not be dialysis dependent

- Patients must be able to swallow tablets

- Patients must not have uncontrolled asthma

- Patients must not co-enroll on other treatment trials

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer on
active surveillance, adequately treated stage I or II cancer from which the patient is
currently in complete remission, or any other cancer from which the patient has been
disease free for five years

- Patients must not be pregnant or nursing due to potential fetal or nursing infant
harm; women/men of reproductive potential must have agreed to use an effective
contraceptive method, a woman is considered to be of "reproductive potential" if she
has had menses at any time in the preceding 12 consecutive months; in addition to
routine contraceptive methods, "effective contraception" also includes heterosexual
celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal
ligation; however, if at any point a previously celibate patient chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive measures

- Patients must be willing to submit blood specimens

- Sites must seek additional patient consent for the future use of specimens

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines

- As a part of the OPEN registration process the treating institution's identity is
provided in order to ensure that the current (within 365 days) date of institutional
review board approval for this study has been entered in the system

- STEP 2 REGISTRATION (Randomization)

- Patients must not be registered to step 2 until receiving confirmation from the ECHO
Core Lab that the patient?s LVEF by echocardiogram was >= 50% by central review;
patients must be registered within 5 calendar days of receiving the e-mail
notification

- Site must verify that there is no known change in the step 1 eligibility since initial
registration
We found this trial at
513
sites
Greenville, South Carolina 29615
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Greenville, SC
Click here to add this to my saved trials
2545 Schoenersville Rd
Bethlehem, Pennsylvania 18017
(484) 884-2200
Lehigh Valley Hospital - Muhlenberg At Lehigh Valley Health Network, we continually go the extra...
?
mi
from
Bethlehem, PA
Click here to add this to my saved trials
Bremerton, Washington 98310
?
mi
from
Bremerton, WA
Click here to add this to my saved trials
1 Hurley Plaza
Flint, Michigan 48503
(810) 262-9000
Hurley Medical Center From its founding in 1908, Hurley Medical Center has devoted itself to...
?
mi
from
Flint, MI
Click here to add this to my saved trials
524 South Park Street
Kalamazoo, Michigan 49007
(269) 341-7654
Bronson Methodist Hospital Our healthcare system serves patients and families throughout southwest Michigan and northern...
?
mi
from
Kalamazoo, MI
Click here to add this to my saved trials
200 North Park Street
Kalamazoo, Michigan 49007
(269) 382-2500
West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
?
mi
from
Kalamazoo, MI
Click here to add this to my saved trials
4805 Northeast Glisan Street
Portland, Oregon 97213
(503) 215-1111
Providence Portland Medical Center We strive to give those we serve exceptional, compassionate health care...
?
mi
from
Portland, OR
Click here to add this to my saved trials
4502 Medical Drive
San Antonio, Texas 78284
(210) 567-7000
Principal Investigator: Virginia G. Kaklamani
Phone: 210-450-3800
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
?
mi
from
San Antonio, TX
Click here to add this to my saved trials
Seattle, Washington 98104
?
mi
from
Seattle, WA
Click here to add this to my saved trials
808 North 39th Avenue
Yakima, Washington 98902
?
mi
from
Yakima, WA
Click here to add this to my saved trials
98-1079 Moanalua Road
'Aiea, Hawaii 96701
?
mi
from
'Aiea, HI
Click here to add this to my saved trials
'Aiea, Hawaii 96701
?
mi
from
'Aiea, HI
Click here to add this to my saved trials
2226 Liliha Street
'Aiea, Hawaii 96701
?
mi
from
'Aiea, HI
Click here to add this to my saved trials
Aberdeen, Washington 98520
?
mi
from
Aberdeen, WA
Click here to add this to my saved trials
200-298 Avenida Doctor Pedro Albizu Campos
Aguadilla, 00603
?
mi
from
Aguadilla,
Click here to add this to my saved trials
Allentown, Pennsylvania 18103
?
mi
from
Allentown, PA
Click here to add this to my saved trials
Anaconda, Montana 59711
?
mi
from
Anaconda, MT
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
1500 East Medical Center Drive
Ann Arbor, Michigan 48109
800-865-1125
Principal Investigator: Erin F. Cobain
University of Michigan Comprehensive Cancer Center The U-M Comprehensive Cancer Center's mission is the conquest...
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
5301 McAuley Drive
Ann Arbor, Michigan 48197
734-712-3456
Saint Joseph Mercy Hospital St. Joseph Mercy Ann Arbor Hospital is a 537-bed teaching hospital...
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
?
mi
from
Antioch, CA
Click here to add this to my saved trials
1625 Maple Lane
Ashland, Wisconsin 54806
?
mi
from
Ashland, WI
Click here to add this to my saved trials
Atlanta, Georgia 30322
Principal Investigator: Joan L. Kramer
Phone: 404-778-1868
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
550 Peachtree St NE
Atlanta, Georgia 30308
(404) 686-4411
Emory University Hospital Midtown Emory University Hospital Midtown is a 511-bed community-based, acute care teaching...
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Atlanta, Georgia 30342
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Auburn, Washington 98001
?
mi
from
Auburn, WA
Click here to add this to my saved trials
2000 Ogden Ave
Aurora, Illinois 60504
(630) 978-6200
Rush - Copley Medical Center Rush-Copley is proud to be the leading provider of health...
?
mi
from
Aurora, IL
Click here to add this to my saved trials
Bainbridge Island, Washington 98110
?
mi
from
Bainbridge Island, WA
Click here to add this to my saved trials
3325 Pocahontas Road
Baker City, Oregon 97814
?
mi
from
Baker City, OR
Click here to add this to my saved trials
?
mi
from
Ballwin, MO
Click here to add this to my saved trials
4305 New Shepherdsville Road
Bardstown, Kentucky 40004
?
mi
from
Bardstown, KY
Click here to add this to my saved trials
Baton Rouge, Louisiana 70809
?
mi
from
Baton Rouge, LA
Click here to add this to my saved trials
Baton Rouge, Louisiana 70816
?
mi
from
Baton Rouge, LA
Click here to add this to my saved trials
265 Fremont St
Battle Creek, Michigan 49017
(269) 245-8166
Bronson Battle Creek As a proud member of the Battle Creek community, we believe everyone...
?
mi
from
Battle Creek, MI
Click here to add this to my saved trials
Beachwood, Ohio 44122
Principal Investigator: Ayla A. Kessler
Phone: 800-641-2422
?
mi
from
Beachwood, OH
Click here to add this to my saved trials
3535 Pentagon Boulevard
Beavercreek, Ohio 45431
?
mi
from
Beavercreek, OH
Click here to add this to my saved trials
Bel Air, Maryland 21014
Principal Investigator: Ashkan Bahrani
Phone: 443-643-3010
?
mi
from
Bel Air, MD
Click here to add this to my saved trials
Bellevue, Washington 98004
?
mi
from
Bellevue, WA
Click here to add this to my saved trials
Bellingham, Washington 98225
?
mi
from
Bellingham, WA
Click here to add this to my saved trials
1300 Anne Street NW
Bemidji, Minnesota 56601
(218) 751-5430
Sanford Clinic North-Bemidgi Sanford Health is a voluntary, not-for-profit health care organization. Through its entities,...
?
mi
from
Bemidji, MN
Click here to add this to my saved trials
Bend, Oregon 97701
?
mi
from
Bend, OR
Click here to add this to my saved trials
Billings, Montana 59101
?
mi
from
Billings, MT
Click here to add this to my saved trials
300 N. Seventh St.
Bismarck, North Dakota 58501
(701) 323-6000
Sanford Bismarck Medical Center Whether your stay in our hospital is one day for same...
?
mi
from
Bismarck, ND
Click here to add this to my saved trials
43097 Woodward Avenue
Bloomfield, Michigan 48302
?
mi
from
Bloomfield, MI
Click here to add this to my saved trials
1505 Eastland Drive
Bloomington, Illinois 61701
309-662-2102
Illinois CancerCare-Bloomington Illinois CancerCare, P.C. is a comprehensive practice treating patients withcancer andblood diseases. Our...
?
mi
from
Bloomington, IL
Click here to add this to my saved trials
100 E Idaho St
Boise, Idaho 83712
(208) 381-2711
Saint Luke's Mountain States Tumor Institute For more than 100 years, St. Luke
?
mi
from
Boise, ID
Click here to add this to my saved trials
?
mi
from
Boise, ID
Click here to add this to my saved trials
Bolivar, Missouri 65613
?
mi
from
Bolivar, MO
Click here to add this to my saved trials
Bonne Terre, Missouri 63628
?
mi
from
Bonne Terre, MO
Click here to add this to my saved trials
915 Highland Blvd
Bozeman, Montana 59715
(406) 414-5000
Bozeman Deaconess Hospital Bozeman Deaconess Hospital is a Joint Commission certified, licensed Level III trauma...
?
mi
from
Bozeman, MT
Click here to add this to my saved trials
?
mi
from
Brainerd, MN
Click here to add this to my saved trials
Branson, Missouri 65616
?
mi
from
Branson, MO
Click here to add this to my saved trials
?
mi
from
Bremerton, WA
Click here to add this to my saved trials
7575 Grand River Avenue
Brighton, Michigan 48114
?
mi
from
Brighton, MI
Click here to add this to my saved trials
7575 Grand River Avenue
Brighton, Michigan 48114
?
mi
from
Brighton, MI
Click here to add this to my saved trials
Brownstown, Michigan 48183
Principal Investigator: Ding Wang
?
mi
from
Brownstown, MI
Click here to add this to my saved trials
?
mi
from
Bryan, TX
Click here to add this to my saved trials
130 S Bryn Mawr Ave
Bryn Mawr, Pennsylvania 19010
(484) 337-3000
Bryn Mawr Hospital Bryn Mawr Hospital, a nationally recognized community teaching hospital, is conveniently located...
?
mi
from
Bryn Mawr, PA
Click here to add this to my saved trials
?
mi
from
Burbank, CA
Click here to add this to my saved trials
Burien, Washington 98166
?
mi
from
Burien, WA
Click here to add this to my saved trials
Burlington, Massachusetts 01805
Principal Investigator: Krishna S. Gunturu
Phone: 781-744-8027
?
mi
from
Burlington, MA
Click here to add this to my saved trials
201 E Nicollet Blvd
Burnsville, Minnesota 55337
(952) 892-2000
Fairview Ridges Hospital Fairview Ridges Hospital is a 150-bed, Level III Trauma Care facility, offering...
?
mi
from
Burnsville, MN
Click here to add this to my saved trials
3123 Medical Dr
Caldwell, Idaho 83605
?
mi
from
Caldwell, ID
Click here to add this to my saved trials
210 W Walnut St
Canton, Illinois 61520
309-647-5240
Illinois CancerCare - Canton Illinois CancerCare is one of the largest private oncology and hematology...
?
mi
from
Canton, IL
Click here to add this to my saved trials
1600 South Canton Center Road
Canton, Michigan 48188
?
mi
from
Canton, MI
Click here to add this to my saved trials
1600 South Canton Center Road
Canton, Michigan 48188
?
mi
from
Canton, MI
Click here to add this to my saved trials
2600 Sixth St. SW
Canton, Ohio 44710
330.363.4908
Principal Investigator: Sunitha Vemulapalli
Phone: 330-363-6891
Aultman Health Foundation The Aultman Foundation will raise and administer funds in order to support...
?
mi
from
Canton, OH
Click here to add this to my saved trials
211 Saint Francis Drive
Cape Girardeau, Missouri 63703
573-331-3000
Principal Investigator: Bryan A. Faller
Phone: 573-334-2230
Saint Francis Medical Center Saint Francis Medical Center is a 282-bed facility serving more than...
?
mi
from
Cape Girardeau, MO
Click here to add this to my saved trials
789 Mt Auburn Rd
Cape Girardeau, Missouri 63703
(573) 519-4725
Southeast Cancer Center SoutheastHEALTH is a far-reaching network of providers and facilities including Southeast Hospital...
?
mi
from
Cape Girardeau, MO
Click here to add this to my saved trials
Carbondale, Illinois 62902
?
mi
from
Carbondale, IL
Click here to add this to my saved trials
401 North Hooper Street
Caro, Michigan 48723
?
mi
from
Caro, MI
Click here to add this to my saved trials
Carterville, Illinois 62918
?
mi
from
Carterville, IL
Click here to add this to my saved trials
160 S Adams St
Carthage, Illinois 62321
(217) 357-6877
Illinois CancerCare - Carthage Illinois CancerCare, P.C. is a comprehensive practice treating patients withcancer andblood...
?
mi
from
Carthage, IL
Click here to add this to my saved trials
Centerville, Ohio 45459
?
mi
from
Centerville, OH
Click here to add this to my saved trials
?
mi
from
Centerville, OH
Click here to add this to my saved trials
Centralia, Illinois 62801
?
mi
from
Centralia, IL
Click here to add this to my saved trials
Centralia, Washington 98531
?
mi
from
Centralia, WA
Click here to add this to my saved trials
Chadds Ford, Pennsylvania 19317
?
mi
from
Chadds Ford, PA
Click here to add this to my saved trials
Chardon, Ohio 44024
Principal Investigator: Ayla A. Kessler
Phone: 800-641-2422
?
mi
from
Chardon, OH
Click here to add this to my saved trials
171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Principal Investigator: Frank J. Brescia
Phone: 843-792-9321
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
?
mi
from
Charleston, SC
Click here to add this to my saved trials
Chattanooga, Tennessee 37404
?
mi
from
Chattanooga, TN
Click here to add this to my saved trials
775 South Main Street
Chelsea, Michigan 48118
?
mi
from
Chelsea, MI
Click here to add this to my saved trials
14650 East Old US Highway 12
Chelsea, Michigan 48118
?
mi
from
Chelsea, MI
Click here to add this to my saved trials
1200 West Harrison Stree
Chicago, Illinois 60607
(312) 996-4350
Principal Investigator: Kent F. Hoskins
Phone: 312-355-3046
Univ of Illinois A major research university in the heart of one of the world's...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Chico, California 95926
?
mi
from
Chico, CA
Click here to add this to my saved trials
Cincinnati, Ohio 45242
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Cincinnati, Ohio 45220
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Cincinnati, Ohio 45255
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Cincinnati, Ohio 45247
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
9280 SE Sunnybrook Blvd #100
Clackamas, Oregon 97015
(503) 513-3300
Clackamas Radiation Oncology Center State-of-the-art technology and compassionate care come together at Clackamas Radiation Oncology...
?
mi
from
Clackamas, OR
Click here to add this to my saved trials
?
mi
from
Clackamas, OR
Click here to add this to my saved trials
5680 Bow Pointe Drive
Clarkston, Michigan 48346
?
mi
from
Clarkston, MI
Click here to add this to my saved trials
31500 Telegraph Road
Clarkston, Michigan 48346
?
mi
from
Clarkston, MI
Click here to add this to my saved trials
5680 Bow Pointe Drive
Clarkston, Michigan 48346
?
mi
from
Clarkston, MI
Click here to add this to my saved trials