Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery
Status: | Completed |
---|---|
Conditions: | Colorectal Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 3/28/2019 |
Start Date: | April 2006 |
End Date: | August 2015 |
ASSURE: Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma
This randomized phase III trial studies sunitinib malate and sorafenib tosylate to see how
well they work compared to placebo in treating patients with kidney cancer that has been
removed by surgery. Sunitinib malate and sorafenib tosylate may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to
the tumor. Giving sunitinib malate or sorafenib tosylate after surgery may kill any tumor
cells that remain after surgery. It is not yet known whether sunitinib malate or sorafenib
tosylate is more effective than placebo in treating kidney cancer.
well they work compared to placebo in treating patients with kidney cancer that has been
removed by surgery. Sunitinib malate and sorafenib tosylate may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to
the tumor. Giving sunitinib malate or sorafenib tosylate after surgery may kill any tumor
cells that remain after surgery. It is not yet known whether sunitinib malate or sorafenib
tosylate is more effective than placebo in treating kidney cancer.
PRIMARY OBJECTIVES:
I. To demonstrate an improvement in disease-free survival in locally advanced renal cell
carcinoma patients randomly assigned to adjuvant sunitinib (sunitinib malate) (Arm A) or
sorafenib (sorafenib tosylate) (Arm B) versus placebo (Arm C) after radical or partial
nephrectomy.
SECONDARY OBJECTIVES:
I. To compare overall survival of patients randomized to each of the two regimens with
placebo.
II. To further define the toxicity of prolonged administration of sunitinib or sorafenib in
this patient population.
III. To evaluate cardiac function in each arm
OTHER PRE-SPECIFIED OBJECTIVES:
I. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: novel approaches to assess angiogenesis markers in tissue, blood and urine
as predictors of disease-free survival and of therapeutic benefit.
II. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: the frequency of oncogene and tumor suppressor gene mutations as predictors
of disease-free survival and therapeutic benefit.
III. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: tumor and genetic polymorphisms as predictors of disease-free survival and
therapeutic benefit.
IV. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: deoxyribonucleic acid (DNA) methylation profiles as predictors of outcome
and of therapeutic benefit.
V. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: The relationship of polymorphisms in drug metabolizing enzymes with steady
state concentrations of sorafenib and sunitinib in selected patients.
VI. To study the effect of vascular endothelial growth factor (VEGF) targeted therapy on
circulating endothelial cells and circulating endothelial progenitors.
VII. To prospectively assess patient-reported fatigue in order to compare the magnitude and
trajectory of fatigue among renal cell carcinoma (RCC) patients randomized to adjuvant
sunitinib (Arm A) or sorafenib (Arm B) to placebo (Arm C). (Quality of life objectives) VIII.
To evaluate the Patient Reported Outcomes Measurement Information System (PROMIS)
Fatigue-Short Form (SF)1, a newly developed state-of-the-science PROMIS measure for fatigue
and to calibrate the PROMIS Fatigue-SF1 with the established, validated Functional Assessment
of Chronic Illness Therapy (FACIT) -Fatigue scale. (Quality of life objectives)
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM A: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive
sunitinib malate orally (PO) once daily (QD) for 4 weeks and placebo sorafenib tosylate PO QD
or twice daily (BID) for 6 weeks.
ARM B: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive
sorafenib tosylate PO QD or BID for 6 weeks and placebo sunitinib malate PO QD for 4 weeks
followed.
ARM C: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive
placebo sorafenib tosylate as in Arm A and placebo sunitinib malate as in Arm B.
In all arms, treatment repeats every 6 weeks for 9 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then every 12 months for 5 years.
I. To demonstrate an improvement in disease-free survival in locally advanced renal cell
carcinoma patients randomly assigned to adjuvant sunitinib (sunitinib malate) (Arm A) or
sorafenib (sorafenib tosylate) (Arm B) versus placebo (Arm C) after radical or partial
nephrectomy.
SECONDARY OBJECTIVES:
I. To compare overall survival of patients randomized to each of the two regimens with
placebo.
II. To further define the toxicity of prolonged administration of sunitinib or sorafenib in
this patient population.
III. To evaluate cardiac function in each arm
OTHER PRE-SPECIFIED OBJECTIVES:
I. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: novel approaches to assess angiogenesis markers in tissue, blood and urine
as predictors of disease-free survival and of therapeutic benefit.
II. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: the frequency of oncogene and tumor suppressor gene mutations as predictors
of disease-free survival and therapeutic benefit.
III. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: tumor and genetic polymorphisms as predictors of disease-free survival and
therapeutic benefit.
IV. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: deoxyribonucleic acid (DNA) methylation profiles as predictors of outcome
and of therapeutic benefit.
V. To prospectively collect tumor and biological specimens to assess their characteristics
and associations: The relationship of polymorphisms in drug metabolizing enzymes with steady
state concentrations of sorafenib and sunitinib in selected patients.
VI. To study the effect of vascular endothelial growth factor (VEGF) targeted therapy on
circulating endothelial cells and circulating endothelial progenitors.
VII. To prospectively assess patient-reported fatigue in order to compare the magnitude and
trajectory of fatigue among renal cell carcinoma (RCC) patients randomized to adjuvant
sunitinib (Arm A) or sorafenib (Arm B) to placebo (Arm C). (Quality of life objectives) VIII.
To evaluate the Patient Reported Outcomes Measurement Information System (PROMIS)
Fatigue-Short Form (SF)1, a newly developed state-of-the-science PROMIS measure for fatigue
and to calibrate the PROMIS Fatigue-SF1 with the established, validated Functional Assessment
of Chronic Illness Therapy (FACIT) -Fatigue scale. (Quality of life objectives)
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM A: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive
sunitinib malate orally (PO) once daily (QD) for 4 weeks and placebo sorafenib tosylate PO QD
or twice daily (BID) for 6 weeks.
ARM B: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive
sorafenib tosylate PO QD or BID for 6 weeks and placebo sunitinib malate PO QD for 4 weeks
followed.
ARM C: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive
placebo sorafenib tosylate as in Arm A and placebo sunitinib malate as in Arm B.
In all arms, treatment repeats every 6 weeks for 9 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then every 12 months for 5 years.
Pre-Registration Inclusion Criteria:
- Pre-surgical criteria:
- Patients must have primary-intact renal cell carcinoma, eligible for nephrectomy
with curative intent
- Tumors >= 4 cm AND/OR macroscopic fully resectable nodes AND/OR surgically
resectable renal vein thrombus AND/OR surgically resectable inferior vena caval
thrombus by radiologic criteria to be clinically >= pT1bNany (resectable) M0
disease
- Multifocal ipsilateral renal cell carcinoma is allowed provided fully resectable
and does not exceed inclusion criteria
- Patients must have corrected QT (QTc) interval < 500 msec on baseline
electrocardiogram (EKG)
- Women of child-bearing potential and men must agree to use an accepted and effective
method of contraception prior to study entry and for the duration of study
participation; should a woman become pregnant while participating in this study, she
should inform her treating physician immediately; if a man impregnates a woman while
participating in this study, he should inform his treating physician immediately as
well
- The date of randomization must be less than 12 weeks after the date of surgery;
patients must have recovered from any surgical related complications
Inclusion Criteria at Randomization:
- Within 4 weeks prior to randomization, patients must meet preoperative eligibility
requirements
- Patients must complete surgery less than 12 weeks prior to randomization
- Patients must have histologically or cytologically confirmed renal cell carcinoma.
Using 2002 (American Joint Committee on Cancer [AJCC] 6th edition) TNM Staging,
patients must be one of the following:
- pT1b G3-4 N0 (or pNX where clinically N0) M0
- pT2 G (any) N0 (or pNX where clinically N0) M0
- pT3 G (any) N0 (or pNX where clinically N0) M0
- pT4 G (any) N0 (or pNX where clinically N0) M0 or
- T (any) G (any) N+ (fully resected) M0
- Patients with microvascular invasion of the renal vein of any grade or stage
(as long as M0) are also eligible
- Patients must have undergone a full surgical resection (radical nephrectomy
or partial nephrectomy) by either open or laparoscopic technique; clinical
evidence of lymph node positivity requires removal of all clinically
positive nodes; surgeons should designate extent of node dissection; all
surgical specimens must have negative margins; patients with positive renal
vein margins are eligible unless there is invasion of the renal vein wall at
the margin (provided no other margins are positive)
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-1
- Patients must have an absolute baseline left ventricular ejection fraction (LVEF) of
>= 50% by multigated acquisition (MUGA) scan within 4 weeks prior to randomization
- Patients must have paraffin-embedded tumor specimen available for central core review
of tumor histology and other correlative studies; tumor samples will be shipped as
specified
- Patients must have no evidence of residual or metastatic renal cell cancer as
documented on computed tomography (CT) scans of the chest, abdomen, and pelvis, all
with oral and intravenous (IV) contrast (magnetic resonance imaging [MRI] scans of the
abdomen and pelvis with gadolinium and a non-contrast CT of the chest may be
substituted if patient is not able to have CT scans with intravenous contrast);
patients unable to tolerate either gadolinium or IV contrast should not participate in
this study (limitations to a patient's renal function should be taken into
consideration when screening for this study)
- Scans must be obtained within 4 weeks of randomization; changes on these scans
that are felt to be post surgical must be documented
- Patients without reported lymph nodes in the resected surgical specimen and a
reported pathologic stage (post-nephrectomy) of pNX MUST undergo a post-operative
contrast-enhanced CT scan (or MRI with gadolinium) within 4 weeks of
randomization to document that there is no evidence of residual disease
- Absolute granulocyte count (AGC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Serum creatinine =< 2.0 x upper limit of normal (ULN) or calculated creatinine
clearance (CrCl) >= 30 mL/min (neither drug is cleared by the kidney)
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate
transaminase (SGPT) =< 2.5 x ULN
- Patients must be able to swallow pills
Exclusion Criteria:
- History of distant metastases
- Prior anti-cancer therapy for renal cell carcinoma in either the adjuvant or
neoadjuvant setting; this includes metastatectomy for renal cell carcinoma, or
radiation therapy to the renal bed
- Other current malignancies, other than basal cell skin cancer, squamous cell skin
cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast;
patients with other malignancies are eligible if they have been continuously
disease-free for >= 5 years prior to the time of registration
- Serious intercurrent illness including, but not limited to, the following: clinically
significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial
infarction, unstable angina); New York Heart Association grade II or greater
congestive heart failure; serious cardiac arrhythmia requiring medication; grade II or
greater peripheral vascular disease; or psychiatric illness/social situations that
would limit compliance with study requirements
- Any of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident or transient
ischemic attack, or pulmonary embolism
- Ongoing ventricular cardiac dysrhythmias of National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 grade >= 2; history of
serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular
fibrillation [VF] >= 3 beats in a row); ongoing atrial fibrillation
- Hypertension that cannot be controlled by medications (>= diastolic blood pressure 100
mm Hg despite optimal medical therapy)
- Pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be
maintained in the normal range with medication
- Pregnant or breastfeeding; all females of childbearing potential must have a blood
test or urine study within 2 weeks prior to pre-registration to rule out pregnancy; if
pre-registration occurs prior to surgery, the blood or urine study must be repeated
within 2 weeks prior to randomization to rule out pregnancy; (note: should a woman
become pregnant while participating in this study, she should inform her treating
physician immediately)
- Patients with known human immunodeficiency virus (HIV)
- Collecting duct carcinomas or medullary carcinomas
- Patients taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin,
carbamazepine or phenobarbital), St John's Wort, ketoconazole, dexamethasone, the
dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil,
indapamide or flecainide), haloperidol, risperidone, rifampin, grapefruit, or
grapefruit juice within two weeks of randomization and during the course of therapy;
(medications are not prohibited unless listed above); topical and inhaled steroids are
permitted
- Receiving any other investigational anti-cancer agents during the period on study
- Serious intercurrent illness, including ongoing or active infection requiring parental
antibiotics
We found this trial at
900
sites
Click here to add this to my saved trials
1201 Camino de Salud Northeast
Albuquerque, New Mexico 87131
Albuquerque, New Mexico 87131
(505) 272-4946
University of New Mexico Cancer Center It’s been 40 years since the New Mexico State...
Click here to add this to my saved trials
Harold Alfond Center for Cancer Care MaineGeneral's Harold Alfond Center for Cancer Care (HACCC) is...
Click here to add this to my saved trials
Suburban Hospital Suburban Hospital is a community-based, not-for-profit hospital serving Montgomery County and the surrounding...
Click here to add this to my saved trials
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
Click here to add this to my saved trials
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
Click here to add this to my saved trials
1 South Prospect Street
Burlington, Vermont 05401
Burlington, Vermont 05401
802-656-8990
Click here to add this to my saved trials
1300 Jefferson Park Avenue
Charlottesville, Virginia 22908
Charlottesville, Virginia 22908
434-243-6784
University of Virginia Cancer Center We are fortunate in having state of the art clinical...
Click here to add this to my saved trials
City of Hope Comprehensive Cancer Center City of Hope is a leading research and treatment...
Click here to add this to my saved trials
Hurley Medical Center From its founding in 1908, Hurley Medical Center has devoted itself to...
Click here to add this to my saved trials
Holy Cross Hospital While spirituality plays an essential role in the way that we minister...
Click here to add this to my saved trials
Brooke Army Medical Center Brooke Army Medical Center (BAMC) is the Flagship of Army Medicine!...
Click here to add this to my saved trials
Click here to add this to my saved trials
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
Click here to add this to my saved trials
340 Medical Pkwy
Greer, South Carolina 29650
Greer, South Carolina 29650
(864) 334-4900
Cancer Centers of the Carolinas - Greer Medical Oncology Cancer Centers of the Carolinas is...
Click here to add this to my saved trials
University of Mississippi Medical Center The University of Mississippi Medical Center, located in Jackson, is...
Click here to add this to my saved trials
Click here to add this to my saved trials
Bronson Methodist Hospital Our healthcare system serves patients and families throughout southwest Michigan and northern...
Click here to add this to my saved trials
West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
Click here to add this to my saved trials
Kinston Medical Specialists offers comprehensive medical services for all ages. Whether it’s a case of...
Click here to add this to my saved trials
Click here to add this to my saved trials
1800 West Charleston Boulevard
Las Vegas, Nevada 89102
Las Vegas, Nevada 89102
(702) 383-2000
University Medical Center of Southern Nevada University Medical Center is dedicated to providing the highest...
Click here to add this to my saved trials
Click here to add this to my saved trials
529 West Markham Street
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
(501) 686-7000
University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) in...
Click here to add this to my saved trials
Medical Center of Central Georgia Navicent Health is a designated Level I Trauma Center and...
Click here to add this to my saved trials
North Shore University Hospital North Shore-LIJ Health System includes 16 award-winning hospitals and nearly 400...
Click here to add this to my saved trials
Beth Israel Med Ctr The physicians and staff of Mount Sinai Beth Israel's Heart Institute...
Click here to add this to my saved trials
4805 Northeast Glisan Street
Portland, Oregon 97213
Portland, Oregon 97213
(503) 215-1111
Providence Portland Medical Center We strive to give those we serve exceptional, compassionate health care...
Click here to add this to my saved trials
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
Click here to add this to my saved trials
Rhode Island Hospital Founded in 1863, Rhode Island Hospital in Providence, RI, is a private,...
Click here to add this to my saved trials
401 College Street
Richmond, Virginia 23298
Richmond, Virginia 23298
(804) 828-0450
Virginia Commonwealth University Massey Cancer Center Founded in 1974, VCU Massey Cancer Center is a...
Click here to add this to my saved trials
University of Rochester The University of Rochester is one of the country's top-tier research universities....
Click here to add this to my saved trials
4502 Medical Drive
San Antonio, Texas 78284
San Antonio, Texas 78284
(210) 567-7000
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
Click here to add this to my saved trials
Click here to add this to my saved trials
Avera Cancer Institute Avera, the health ministry of the Benedictine and Presentation Sisters, is a...
Click here to add this to my saved trials
601 South Sherman Street
Spokane, Washington 99202
Spokane, Washington 99202
(509) 228-1000
Cancer Care Northwest - Spokane South Cancer Care Northwest is the Inland Northwest’s premier cancer...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Abington Memorial Hospital Abington Memorial Hospital (AMH) is a 665-bed, regional referral center and teaching...
Click here to add this to my saved trials
Click here to add this to my saved trials
Bixby Medical Center ProMedica's Mission is to improve your health and well-being. Which is why,...
Click here to add this to my saved trials
Click here to add this to my saved trials
Akron General Medical Center It
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
McFarland Clinic PC-William R Bliss Cancer Center The William R. Bliss Cancer Center at Mary...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Saint Joseph Mercy Hospital St. Joseph Mercy Ann Arbor Hospital is a 537-bed teaching hospital...
Click here to add this to my saved trials
1500 East Medical Center Drive
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
800-865-1125
University of Michigan Comprehensive Cancer Center The U-M Comprehensive Cancer Center's mission is the conquest...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
5665 Peachtree Dunwoody Rd NE
Atlanta, Georgia 30342
Atlanta, Georgia 30342
(678) 843-7001
Saint Joseph's Hospital of Atlanta Founded by the Sisters of Mercy in 1880, Saint Joseph
Click here to add this to my saved trials
Piedmont Hospital For more than a century, Piedmont Healthcare has been a recognized leader in...
Click here to add this to my saved trials
Northside Hospital Northside Hospital-Atlanta (in Sandy Springs) opened in 1970. The original facility had 250...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Medical Center of Aurora At The Medical Center of Aurora and Centennial Medical Plaza patients...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
22 South Greene Street
Baltimore, Maryland 21201
Baltimore, Maryland 21201
410-328-7904
University of Maryland Greenebaum Cancer Center The University of Maryland Marlene and Stewart Greenebaum Cancer...
Click here to add this to my saved trials
Greater Baltimore Medical Center The 255-bed medical center (acute and sub-acute care) is located on...
Click here to add this to my saved trials
401 North Broadway
Baltimore, Maryland 21287
Baltimore, Maryland 21287
410-955-5000
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
Click here to add this to my saved trials
Eastern Maine Medical Center Located in Bangor, Eastern Maine Medical Center (EMMC) serves communities throughout...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Bronson Battle Creek As a proud member of the Battle Creek community, we believe everyone...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Mary Rutan Hospital The hospital was endowed by the sale of a farm in Ridgeway...
Click here to add this to my saved trials
Click here to add this to my saved trials
Sanford Clinic North-Bemidgi Sanford Health is a voluntary, not-for-profit health care organization. Through its entities,...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials