Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Duke University
Novartis
Information provided by (Responsible Party):
David F. McDermott, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00827359
First received: January 21, 2009
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to determine if certain features of tumor specimens sampled prior to therapy can predict for the likelihood of responding to everolimus.


Condition Intervention Phase
Renal Cell Carcinoma
Renal Cancer
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To prospectively validate the expression of phospho-Akt and phospho-S6 as predictive biomarkers of responsiveness to everolimus. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate the progression-free survival in patients with advanced RCC treated with everolimus. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To determine the objective response rate to everolimus in patients with advanced RCC. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To assess in an exploratory fashion the predictive value of PML, phospho-TSC (S664), phospho-PRAS40, eIF4E, and FOXO expression with respect to response to everolimus. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2009
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
This is a single-arm study. All patients will receive everolimus.
Drug: Everolimus
Tablet form taken orally once a day

Detailed Description:
  • Participants will undergo a CT or ultrasound guided biopsy of an accessible tumor lesion before beginning the study medication.
  • Everolimus tablets will be taken orally once a day. Participants will undergo a physical exam and will be asked questions about their general health and specific questions about any problems they might be having. Photographs will be taken of the tumor to assess the response to treatment. This will be done by a CT or MRI scan. Blood tests will be performed every 4 weeks. In addition, blood for research purposes will be done on day 1 of every other cycle. A urine test will be done every 4 weeks.
  Eligibility

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

Inclusion Criteria:

  • Patients must have at least one site of disease which in the opinion of the investigator is safely accessible by CT guided biopsy or metastasectomy. Safely accessible metastatic disease will be defined to include those lesions which are palpable with no overlying viscera and are at least 2cm in size. Given the paucity of subcutaneous lesions in RCC, lesions which are felt to be safe to biopsy will also be allowed. These lesions include pleural-based tumors, peripheral liver lesions, kidney lesions and bone lesions with exophytic soft tissue component. As with palpable lesions, these other lesions should be at least 2cm in size with no overlying viscera.
  • At least one measurable site of disease, other than the biopsy site, according to RECIST criterial that has not been previously irradiated. Th the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
  • Metastatic renal carcinoma with histologic confirmation by the treating center of either primary or a metastatic lesion. Non-clear cell histologies will be allowed
  • 18 years of age or older
  • Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)
  • ECOG Performance status of 1 or less
  • Adequate bone marrow, liver and renal function as outlined in the protocol
  • Fasting serum cholesterol < 300mg/dL OR < 7.75 mmol/L AND fasting triglycerides < 2.5 x ULN
  • Life expectancy of greater than 6 months

Exclusion Criteria:

  • Prior treatment with any investigation drug within the preceding 4 weeks
  • Chronic treatment with systemic steroids or another immunosuppressive agent
  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Treated brain metastases will be allowed. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS: Gamma Knife, LINAC or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection performed within 3 months prio to day 1 will be excluded.
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Uncontrolled diabetes mellitus as defined by a fasting serum > 1.5 x ULN
  • A known history of HIV seropositivity.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus
  • Patients with active, bleeding diathesis or on systemic anticoagulation. Aspirin is permitted.
  • Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control.
  • Patients who have received prior treatment with an mTOR inhibitor.
  • Patients with known hypersensitivity to everolimus or other rapamycins or to its excipients.
  • History of noncompliance to medical regimens
  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: NCT00827359

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Dana-Farber Cancer Institute
Duke University
Novartis
Investigators
Principal Investigator: David F McDermott, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: David F. McDermott, MD, Director of Biologic Therapy Program, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00827359     History of Changes
Other Study ID Numbers: 08-313
Study First Received: January 21, 2009
Last Updated: October 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
everolimus

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

ClinicalTrials.gov processed this record on October 29, 2014