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:
Southwest Oncology Group (SWOG) Research Base
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00326898
First received: May 16, 2006
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This randomized phase III trial is studying 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
Papillary Renal Cell Carcinoma
Stage I Renal Cell Cancer
Stage II Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: sorafenib tosylate
Drug: sunitinib malate
Other: placebo
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
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 6.5 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 to 8.08 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.

  • Decreases in left ventricular ejection fraction (LVEF) in patients treated with sunitinib or sorafenib [ Time Frame: From 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: From baseline to up to 8 weeks after final treatment ] [ Designated as safety issue: Yes ]
  • Scan frequency in preventing CHF [ Time Frame: Up to 6 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.

  • Quality of life (QOL) assessed by Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Subscale the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-SF1 measure [ Time Frame: From 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.


Estimated Enrollment: 1923
Study Start Date: April 2006
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (sunitinib malate, placebo)
Patients receive oral sunitinib malate once daily for 4 weeks followed by rest for 2 weeks and oral placebo for sorafenib tosylate twice daily for 6 weeks.
Drug: sunitinib malate
Given orally
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm B (sorafenib tosylate, placebo)
Patients receive oral sorafenib tosylate twice daily for 6 weeks and oral placebo for sunitinib malate once daily for 4 weeks followed by rest for 2 weeks..
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Placebo Comparator: Arm C (placebo)
Patients receive oral placebo for sorafenib tosylate as in arm A and oral placebo for sunitinib malate as in arm B.
Other: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed renal cell carcinoma, including any of the following subtypes:

    • Clear cell carcinoma
    • Nonclear cell carcinoma

      • No collecting duct or medullary carcinomas
  • Meets 1 of the following risk categories:

    • Intermediate high-risk disease

      • pT1b, G3-4 N0 (or pNX where clinically N0) M0
      • pT2, G1-2 N0 (or pNX where clinically N0) M0
      • pT2, G3-4 N0 (or pNX where clinically N0) M0
      • pT3a, G1-2 (as long as pT3a is not due to adrenal involvement) N0 (or pNX where clinically N0) M0
      • Patients with microvascular invasion of the renal vein of pT1a-pT3a (as long as pT3a is not due to adrenal involvement and grade 1-2) N0 (or pNX where clinically N0) M0
    • Very high-risk disease

      • pT3a, G3-4 (or any grade pT3a if due to adrenal involvement) N0 (or pNX where clinically N0) M0
      • pT3b-c G any N0 (or pNX where clinically N0) M0
      • pT4 G N0 (or pNX where clinically N0) M0 any
      • pT any G any N+
      • Patients with microvascular invasion of the renal vein with above other characteristics
  • Planning to start study treatment between 4-12 weeks after radical or partial nephrectomy

    • Underwent full surgical resection (i.e., radical or partial nephrectomy) by either open or laparoscopic technique within the past 3-10 weeks

      • Clinical evidence of lymph node positivity requires complete regional lymphadenectomy
      • All surgical specimens must have negative margins
    • Planning to undergo the above surgical resection AND meets all of the following criteria:

      • Primary intact renal cell carcinoma, eligible for nephrectomy with curative intent
      • pT1b-4, N0 or any fully resectable N (i.e., N1-2), M0 disease by radiologic criteria, meeting any of the following criteria:

        • Tumors ≥ 4 cm
        • Macroscopic fully resectable nodes
        • Surgically resectable renal vein thrombus
        • Surgically resectable inferior vena caval thrombus by radiologic criteria
      • Multifocal ipsilateral renal cell carcinoma allowed provided fully resectable and does not exceed inclusion criteria
  • No evidence of residual or metastatic renal cell cancer by chest, abdomen, and pelvic CT scan with oral and IV contrast (or MRI scan of the abdomen and pelvis with gadolinium and a CT scan of the chest with or without IV contrast) within 4 weeks of randomization (after radical or partial nephrectomy)

    • Patients unable to tolerate either gadolinium or IV contrast should not participate in this study
  • No history of distant metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 2.0 times upper limit of normal (ULN) OR creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 1.5 times ULN
  • SGOT and SGPT ≤ 2.5 times ULN
  • Absolute baseline LVEF ≥ 50% by MUGA within 4 weeks of randomization
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, in situ cervical cancer, or ductal or lobular carcinoma in situ of the breast
  • No serious intercurrent illness, including, but not limited to, any of the following:

    • Clinically significant cardiovascular disease(e.g., uncontrolled hypertension, myocardial infraction, or unstable angina)
    • New York Heart Association class II-IV congestive heart failure
    • Peripheral vascular disease ≥ grade 2
    • Psychiatric illness or social situation that would preclude study compliance
  • At least 6 months since any of the following:

    • Myocardial infarction
    • Severe or unstable angina
    • Coronary or peripheral artery bypass graft
    • Symptomatic congestive heart failure
    • Cerebrovascular accident
    • Transient ischemic attack
    • Pulmonary embolism
  • No ongoing ventricular cardiac dysrhythmias ≥ grade 2
  • No ongoing atrial fibrillation
  • No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
  • QTc interval < 500 msec by baseline EKG
  • No uncontrolled hypertension (i.e., diastolic blood pressure ≥ 100 mm Hg despite optimal medical therapy)
  • No pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained in the normal range with medication
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known HIV infection
  • Able to swallow pills
  • Recovered from prior surgery
  • No prior anticancer therapy for renal cell carcinoma in either the adjuvant or neoadjuvant setting, including any of the following:

    • Metastectomy
    • Radiotherapy to the renal bed
  • At least 2 weeks since prior and no concurrent treatment with any of the following*:

    • Cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital)
    • Hypericum perforatum (St. John's wort)
    • Ketoconazole
    • Dexamethasone
    • Dysrhythmic drugs (i.e., terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide)
    • Haloperidol
    • Risperidone
    • Rifampin
    • Grapefruit juice or grapefruit
  • Concurrent participation in protocol ECOG-E1Y03 allowed
  • No other concurrent investigational anticancer agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00326898

  Show 923 Study Locations
Sponsors and Collaborators
Southwest Oncology Group (SWOG) Research Base
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Investigators
Principal Investigator: Naomi Balzer-Haas Eastern Cooperative Oncology 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
Study First Received: May 16, 2006
Last Updated: April 9, 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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014