Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Southwest Oncology Group
NCIC Clinical Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00326898
First received: May 16, 2006
Last updated: August 19, 2014
Last verified: June 2014
  Purpose

This randomized phase III trial studies sunitinib malate to see how well it works compared to sorafenib tosylate or 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 is more effective than sorafenib tosylate or placebo in treating kidney cancer.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Stage I Renal Cell Cancer
Stage II Renal Cell Cancer
Stage III Renal Cell Cancer
Drug: sorafenib tosylate
Drug: sunitinib malate
Other: placebo
Other: quality-of-life assessment
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: ASSURE: Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: Time from randomization to recurrence, development of second primary cancer, or death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    A weighted mixture of the log hazard rates was used to estimate the effective (increased) hazard rate on the experimental arm. Using this adjusted alternative hazard rate, the target is instead a reduction in the hazard rate of 20% for DFS events when comparing each experimental arm to placebo.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: From the date of registration to up to10 years ] [ Designated as safety issue: No ]
  • DFS among patients with clear cell histology [ Time Frame: Up to 13 years ] [ Designated as safety issue: No ]
    The sequentially rejective method will be used for this analysis.

  • Left ventricular ejection fraction (LVEF) decline in patients treated with sunitinib malate or sorafenib tosylate [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    LVEF decline defined as LVEF below the institutional lower limit of normal, where the drop is at least 16% from baseline.

  • Frequency of clinically significant congestive heart failure (CHF) grade 3 or higher using the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Baseline to up to 8 weeks after final treatment ] [ Designated as safety issue: Yes ]
  • Scan frequency in preventing CHF [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    The incidence of CHF after MUGA scan intervals of 3 months and 6 months will be described along with changes in LVEF over these intervals.

  • Differences in fatigue assessed by FACIT Fatigue Subscale [ Time Frame: Baseline to up to 22 weeks ] [ Designated as safety issue: No ]
    For each of the two instruments, descriptive statistics at each timepoint, including Cronbach's alpha, will be provided. Repeated measures analyses will be used to examine the treatment and time effects on scores. Spearman's correlation coefficient will be used to explore associations between scores on the FACIT Fatigue subscale and scores on the PROMIS Fatigue-SF1.

  • Psychometric properties assessed by the PROMIS Fatigue-SF1 measure [ Time Frame: Baseline to up to 22 weeks ] [ Designated as safety issue: No ]
    For each of the two instruments, descriptive statistics at each timepoint, including Cronbach's alpha, will be provided. Repeated measures analyses will be used to examine the treatment and time effects on scores. Spearman's correlation coefficient will be used to explore associations between scores on the FACIT Fatigue subscale and scores on the PROMIS Fatigue-SF1.


Estimated Enrollment: 1923
Study Start Date: May 2006
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (sunitinib malate, placebo)
Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate PO QD for 4 weeks and placebo sorafenib tosylate PO QD or BID for 6 weeks.
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: placebo
Given PO
Other Name: PLCB
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (sorafenib tosylate, placebo)
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.
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: placebo
Given PO
Other Name: PLCB
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm C (placebo)
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.
Other: placebo
Given PO
Other Name: PLCB
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 no history of distant metastases
  • No prior anti-cancer therapy for renal cell carcinoma is permitted in either the adjuvant or neoadjuvant setting; this includes metastectomy for renal cell carcinoma, or radiation therapy to the renal bed
  • Patients must not have 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
  • Patients must have no 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
  • Patients must not have 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
  • Patient must not have ongoing ventricular cardiac dysrhythmias of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 grade >= 2; patients with a history of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF] >= 3 beats in a row) are also excluded; additionally, patients with ongoing atrial fibrillation are not eligible
  • Patients must have corrected QT (QTc) interval < 500 msec on baseline electrocardiogram (EKG)
  • Patient must not have hypertension that cannot be controlled by medications (>= diastolic blood pressure 100 mm Hg despite optimal medical therapy)
  • Patient must not have pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained in the normal range with medication
  • If female, patient must not be 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)
  • 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
  • Patients with known human immunodeficiency virus (HIV) are excluded
  • ELIGIBILITY CRITERIA FOLLOWING RADICAL OR PARTIAL NEPHRECTOMY
  • The date of randomization must be less than 12 weeks after the date of surgery; patients must have recovered from any surgical related complications
  • Within 4 weeks prior to randomization, patients must meet preoperative eligibility requirements
  • 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 not have collecting duct carcinomas or medullary carcinomas
  • 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
  • Patients must not be 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
  • Patients must not receive any other investigational anti-cancer agents during the period on study
  • Patients must not have a serious intercurrent illness, including ongoing or active infection requiring parental antibiotics
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00326898

  Show 921 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Southwest Oncology Group
NCIC Clinical Trials Group
Investigators
Principal Investigator: Naomi Balzer-Haas ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00326898     History of Changes
Other Study ID Numbers: NCI-2009-00534, NCI-2009-00534, CAN-NCIC-E2805, SWOG-E2805, ECOG-E2805, CDR0000478976, CALGB-E2805, E2805, E2805, U10CA021115, U10CA180820
Study First Received: May 16, 2006
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sorafenib
Sunitinib
Niacinamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014