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Everolimus (RAD001) For Advanced Renal Cell Carcinoma (RCC) Before Kidney Removal

Primary Purpose

Kidney Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
everolimus
Sponsored by
Linda C. Higgins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Kidney Cancer focused on measuring Renal cell carcinoma, Everolimus, Neoadjuvant, advanced kidney cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Advanced (metastatic) RCC
  • Histology: clear cell, papillary or chromophobe
  • 3 out 6 risk factors (by Memorial Sloan Kettering Cancer Center criteria and one additional criterion: multiple sites of metastasis) or not candidates for or refuse sunitinib.
  • Must have at least one measurable metastatic site according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria that has not been previously irradiated.
  • Must be deemed surgical candidates for cytoreductive nephrectomy by the urologist.
  • Age 18 years of age or older
  • Eastern Cooperative Oncology Group (EGOG) PS 0-2
  • Adequate bone marrow function
  • Adequate liver function as shown by:
  • Adequate renal function
  • Fasting serum cholesterol AND fasting triglycerides within normal limits
  • Signed informed consent

Exclusion Criteria:

  • Collecting duct, medullary histologies or sarcomatoid differentiation.
  • Central Nervous System (CNS) or leptomeningeal metastases.
  • Inappropriate candidates for cytoreductive nephrectomy or who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • severely impaired lung function
  • uncontrolled diabetes
  • active (acute or chronic) or uncontrolled severe infections
  • liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • Ineligible for cytoreductive nephrectomy
  • Current or prior systemic anticancer therapies (including chemotherapy, antibody based therapy, or investigational drugs)
  • Other malignancies within the past 3 years except for localized carcinoma of the cervix, basal or squamous cell carcinomas of the skin, or localized prostate cancer with Gleason Score less than 7 treated with radiation or surgery and no evidence of progression.
  • Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 4 weeks of start of enrollment
  • Anticipated major surgery (other than CN) during the course of the study
  • A known history of HIV seropositivity
  • Hepatitis C seropositivity
  • Chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
  • Immunization with attenuated live vaccines within one week of study entry or during study period
  • Known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients
  • Impairment of gastrointestinal function or gastrointestinal disease
  • Active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
  • History of noncompliance to medical regimens
  • Unwilling to or unable to comply with the protocol including mandated biopsies

Sites / Locations

  • UT Southwestern Medical Center
  • Baylor College of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

All subjects will take everolimus

Outcomes

Primary Outcome Measures

Disease Progression Diagnosed by Biopsy
Clinical progression validated by biopsy of metastatic site. Progression-free survival (PFS) will be measured from the post-op treatment start date to either the date the patient is first recorded as having disease progression, or the date of death if the patient dies due to any causes before progression. If a patient is lost to follow-up or removed for toxicities, the patient will be censored as of the last date of contact. Patients who start a new treatment before they progress will be censored as of the date of start of the new treatment. If a patient has not progressed or died, PFS is censored at the date of last follow-up. Patients removed from therapy with everolimus due to toxicities will not be included in the PFS estimation.

Secondary Outcome Measures

Full Information

First Posted
January 27, 2009
Last Updated
February 19, 2016
Sponsor
Linda C. Higgins
Collaborators
University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00831480
Brief Title
Everolimus (RAD001) For Advanced Renal Cell Carcinoma (RCC) Before Kidney Removal
Official Title
Neoadjuvant Everolimus (RAD001)for Advanced RCC Before Cytoreductive Nephrectomy, With Correlative Tumor Studies (Protocol #: 06-08-20-01)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Terminated
Why Stopped
Difficulty in accrual and by the order of the cancer center.
Study Start Date
April 2011 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Linda C. Higgins
Collaborators
University of Texas Southwestern Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this multicenter, pilot, open-label, Phase II clinical trial is to discover if Everolimus(RAD001) is safe and effective in people who have advanced kidney cancer (renal cell carcinoma - RCC). Since 2002, Everolimus has been studied in more than 2500 patients with various types of cancer as a single agent (a drug that is used alone to treat the cancer) or in combination with a number of well known anticancer therapies. Various studies, in animals such as in mice with cancer and in humans with cancer have shown that Everolimus can slow the growth of cancer. Everolimus will be taken in pill form by mouth daily for 3-5 weeks followed by surgery to remove the effected kidney. After 2-4 weeks following the surgery, Everolimus will be resumed at the same dose.
Detailed Description
Everolimus has significantly improved outcomes following prior therapy. This study is a biomarker driven Phase II trial that will assess the activity of everolimus as first-line therapy for renal cell carcinoma. Following initial kidney tumor biopsy, everolimus is administered for 3-5 weeks before cytoreductive nephrectomy and everolimus is then resumed and continued until tumor progression or intolerable toxicities. Any correlation of tumor tissue biomarker changes from initial biopsy to nephrectomy specimen with long-term progression-free survival will be determined. This trial may enable the identification of factors predictive of significant benefit from everolimus administered as first-line therapy by employing the neoadjuvant therapy paradigm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer
Keywords
Renal cell carcinoma, Everolimus, Neoadjuvant, advanced kidney cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
All subjects will take everolimus
Intervention Type
Drug
Intervention Name(s)
everolimus
Other Intervention Name(s)
RAD001, Afinitor
Intervention Description
everolimus 10 mg PO once daily for 3-5 weeks followed by removal of the kidney. Everolimus will begin again between 2 to 4 weeks after surgery.
Primary Outcome Measure Information:
Title
Disease Progression Diagnosed by Biopsy
Description
Clinical progression validated by biopsy of metastatic site. Progression-free survival (PFS) will be measured from the post-op treatment start date to either the date the patient is first recorded as having disease progression, or the date of death if the patient dies due to any causes before progression. If a patient is lost to follow-up or removed for toxicities, the patient will be censored as of the last date of contact. Patients who start a new treatment before they progress will be censored as of the date of start of the new treatment. If a patient has not progressed or died, PFS is censored at the date of last follow-up. Patients removed from therapy with everolimus due to toxicities will not be included in the PFS estimation.
Time Frame
up to one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Advanced (metastatic) RCC Histology: clear cell, papillary or chromophobe 3 out 6 risk factors (by Memorial Sloan Kettering Cancer Center criteria and one additional criterion: multiple sites of metastasis) or not candidates for or refuse sunitinib. Must have at least one measurable metastatic site according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria that has not been previously irradiated. Must be deemed surgical candidates for cytoreductive nephrectomy by the urologist. Age 18 years of age or older Eastern Cooperative Oncology Group (EGOG) PS 0-2 Adequate bone marrow function Adequate liver function as shown by: Adequate renal function Fasting serum cholesterol AND fasting triglycerides within normal limits Signed informed consent Exclusion Criteria: Collecting duct, medullary histologies or sarcomatoid differentiation. Central Nervous System (CNS) or leptomeningeal metastases. Inappropriate candidates for cytoreductive nephrectomy or who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study severely impaired lung function uncontrolled diabetes active (acute or chronic) or uncontrolled severe infections liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis Ineligible for cytoreductive nephrectomy Current or prior systemic anticancer therapies (including chemotherapy, antibody based therapy, or investigational drugs) Other malignancies within the past 3 years except for localized carcinoma of the cervix, basal or squamous cell carcinomas of the skin, or localized prostate cancer with Gleason Score less than 7 treated with radiation or surgery and no evidence of progression. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 4 weeks of start of enrollment Anticipated major surgery (other than CN) during the course of the study A known history of HIV seropositivity Hepatitis C seropositivity Chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed. Immunization with attenuated live vaccines within one week of study entry or during study period Known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients Impairment of gastrointestinal function or gastrointestinal disease Active, bleeding diathesis Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. History of noncompliance to medical regimens Unwilling to or unable to comply with the protocol including mandated biopsies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilad E. Amiel, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Everolimus (RAD001) For Advanced Renal Cell Carcinoma (RCC) Before Kidney Removal

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