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

Neoadjuvant Everolimus (RAD001)for Advanced RCC Before Cytoreductive Nephrectomy, With Correlative Tumor Studies (Protocol #: 06-08-20-01)

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: everolimus

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; All subjects will take everolimus	Drug: everolimus; 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.; Other Names: Afinitor; RAD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to one year

Collaborators and Investigators

• Sponsor: Linda C. Higgins
• Collaborators: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Gilad E. Amiel, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: January 27, 2009
• First Submitted That Met QC Criteria: January 28, 2009
• First Posted (ESTIMATE): January 29, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 21, 2016
• Last Update Submitted That Met QC Criteria: February 19, 2016
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Everolimus; Neoadjuvant; Renal cell carcinoma; advanced kidney cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: H-23409

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED