Trial record 1 of 5 for:    S0931
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S0931, Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Southwest Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01120249
First received: May 7, 2010
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

PURPOSE: This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.


Condition Intervention Phase
Kidney Cancer
Drug: everolimus
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, A Phase III Study

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Compare Recurrence-free survival in those patients randomized to everolimus versus those randomized to placebo. [ Time Frame: up to 10 years after registration ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first documentation of recurrence or death due to any cause. Patients last known to be alive and recurrence-free are censored at date of last contact.


Secondary Outcome Measures:
  • Compare Overall survival in those patients randomized to everolimus versus those randomized to placebo. [ Time Frame: up to 10 years after registration ] [ Designated as safety issue: No ]
    Measured from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

  • Compare Toxicity between the two study arms [ Time Frame: up to 54 weeks of treatment ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.


Estimated Enrollment: 1218
Study Start Date: April 2011
Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral everolimus once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
Drug: everolimus
Given orally
Placebo Comparator: Arm II
Patients receive oral placebo once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
Other: placebo
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • to compare recurrence-free survival in renal carcinoma patients randomly assigned to 54 weeks of everolimus versus 54 weeks of placebo after nephrectomy or partial nephrectomy.

Secondary

  • To compare the overall survival of patients treated with everolimus vs placebo.
  • To compare qualitative and quantitative toxicity between the two study arms.
  • To bank tissue and biologic specimens for future study of molecular biomarkers relevant to the AKT/mTOR and other pathways implicated in the pathogenesis of renal carcinoma and to investigate their potential predictive and prognostic value.
  • To bank blood specimens for the future study of the relationship between steady-state trough levels of everolimus and relevant side effects (lymphopenia, infection, hyperglycemia, hypercholesterolemia, hypertriglyceridemia) in patients treated on this study with everolimus.

OUTLINE: This is a multicenter study.

Patients are stratified according to pathologic stage (intermediate high-risk vs very high-risk), histologic subtype (clear cell vs non-clear cell), and performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral everolimus once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral placebo once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

Archived tumor tissue, plasma, and whole blood samples may be collected periodically for biomarker analysis and other translational studies.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 8 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed renal cell carcinoma

    • Clear cell or non-clear cell allowed

      • No disease of the collecting duct or medullary carcinoma
    • Considered pathologically either intermediate high-risk or very high-risk disease
    • No history of distant metastases
    • Patients with microvascular invasion of the renal vein of any grade or stage (as long as M0) are eligible
  • Have undergone a full surgical resection (radical nephrectomy or partial nephrectomy) including removal of all clinically positive nodes

    • Surgical margins must be negative

      • 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 be registered within 84 days after the date of the first surgical resection of the first tumor
  • No evidence of residual or metastatic renal cell cancer on CT scan of the chest, abdomen, and pelvis (all with oral and IV contrast) performed after nephrectomy and within 28 days before registration

    • MRI scans of the abdomen and pelvis with gadolinium and a non-contrast CT scan of the chest may be substituted if the patient is not able to have CT scans with IV contrast

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Serum creatinine ≤ 2.0 times upper limit of normal (ULN) OR calculated creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 1.5 times ULN
  • SGOT and SGPT ≤ 2.5 times ULN
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for up to 8 weeks after completion of study treatment
  • Able to take oral medications
  • Patients must not have any of the following:

    • NYHA class III-IV cardiac disease (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort)
    • Unstable angina pectoris
    • Myocardial infarction within the past 6 months
    • Serious uncontrolled cardiac arrhythmia
  • Patients must NOT have liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh Class C)
  • HBV and HCV testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection
  • Must be able to take oral medications
  • No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • No known history of HIV seropositivity
  • No known uncontrolled, underlying pulmonary disease (spirometry and DLCO ≤ 50% of predicted OR oxygen saturation ≤ 88% at rest on room air)
  • No uncontrolled hyperlipidemia (fasting serum cholesterol > 300 mg/dL AND fasting triglycerides > 2.5 times ULN) obtained within 28 days prior to registration

    • Optimal lipid control must be achieved before registration and monitored during protocol treatment
  • No uncontrolled diabetes mellitus (defined by fasting serum glucose > 1.5 times ULN) obtained within 28 days prior to registration.

    • Optimal glucose control must be achieved before registration and monitored during protocol treatment
  • No prior malignancies except for any of the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I or stage II cancer from which the patient is currently in complete remission
    • Any other cancer from which the patient has been disease-free for 5 years
  • No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to their excipients
  • No contraindications to receiving either IV iodine-based contrast or gadolinium

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Patients must have recovered from any surgery-related complications
  • No prior anticancer therapy for renal cell carcinoma including systemic therapy in the adjuvant or neoadjuvant setting, immunotherapy, investigational therapy, surgical metastasectomy, or radiotherapy
  • More than 14 days since prior and no concurrent strong CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, voriconazole, posaconazole, fluvoxamine, nefazodone, nelfinavir, or ritonavir) or strong CYP3A4 inducers (i.e., phenytoin, rifampin, or rifabutin)
  • More than 7 days since prior and no concurrent live vaccines
  • No other concurrent anticancer agents including investigational agents
  • No concurrent chronic treatment with systemic steroids or another immunosuppressive agent

    • Topical or inhaled corticosteroids are allowed
  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: NCT01120249

Contacts
Contact: Gilbert Carrizales 2106148808 gcarrizales@swog.org
Contact: Dana Sparks, MAT 2106148808 ext 1004 dsparks@swog.org

  Show 574 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Christopher W. Ryan, MD OHSU Knight Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT01120249     History of Changes
Other Study ID Numbers: CDR0000668388, S0931, U10CA032102
Study First Received: May 7, 2010
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
stage I renal cell cancer
stage II renal cell cancer
stage III renal cell cancer
clear cell renal cell carcinoma
papillary renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on October 19, 2014