Everolimus and Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma (RCC)

This study is currently recruiting participants.
Verified March 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01399918
First received: July 20, 2011
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to find out what effects, good and/or bad the combination of two medications, everolimus and bevacizumab, has on kidney cancer. In this clinical trial we are now testing these medications in combination. We think that both together might work better that either drug alone. Importantly, both of these drugs together have been tested in patients with a different type of kidney cancer and patients tolerated the combination well.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: everolimus and bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Everolimus and Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma (RCC)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To evaluate the efficacy of combining everolimus and bevacizumab in patients with advanced RCC of non-clear cell histology [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    the percent of patients alive and progression-free after 6 months of therapy.


Secondary Outcome Measures:
  • Secondary endpoint will be the overall response rate (ORR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    per the international criteria defined by the Response Evaluation Criteria in Solid Tumors Committee

  • To investigate the safety of everolimus and bevacizumab in patients with advanced RCC of non-clear cell histology. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (Gompertz 1825),. Toxicities will be summarized by type and grade using frequencies and rates.


Estimated Enrollment: 34
Study Start Date: July 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: everolimus and bevacizumab
This is a single-institution, single-arm phase II trial of everolimus in combination with bevacizumab in patients with advanced non-clear cell RCC, who have not received prior VEGF-.or mTOR-targeted therapy.
Drug: everolimus and bevacizumab
Cycle length will be defined as 28 days. Treatment will include everolimus 10mg, self administered orally once daily on a continuous schedule (days 1-28), and bevacizumab 10mg/kg, administered intravenously on days 1 and 15 of each cycle. Treatment will be continued until disease progression, major toxicity, or withdrawal from the study for any reason. Dose modification will be permitted based on toxicity. Patients that come off study before 6 months before documented progression/death will be treated as events for the 6 month PFS endpoint.

  Eligibility

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

Inclusion Criteria:

  • Advanced renal cell carcinoma of non-clear cell histology, histologically confirmed by MSKCC pathology. Subtypes include papillary (type 1 and 2), chromophobe, collecting duct (also Bellini duct), medullary and unclassified RCC. Advanced disease is defined as unresectable, locally recurrent disease or metastatic disease. Availability of additional tissue for correlative studies is NOT in inclusion requirement.
  • Evidence of unidimensionally measurable disease per RECIST 1.1 (Eisenhauer, Therasse et al. 2009). Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
  • Adequate organ function as defined by the following criteria:
  • Absolute neutrophil count (ANC) ≥1,500/μL
  • Platelets ≥100,000/μL
  • Hemoglobin ≥9.0 g/dL
  • Serum calcium ≤12.0 mg/dL
  • Serum creatinine ≤1.5 x ULN
  • Total serum bilirubin ≤1.5 x ULN
  • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤2.5 x local laboratory upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due to underlying malignancy
  • INR ≤1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at time of study entry.)
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.

Karnofsky performance status ≥ 70 %.

  • 18 years of age or older.
  • Ability to swallow oral medication.
  • Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to undergoing study screening procedures.
  • Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

  • Patients who have received prior systemic therapy for their RCC with VEGF pathway inhibitor (such as sunitinib, sorafenib, and bevacizumab) or with mTOR inhibitors (such as sirolimus, temsirolimus, everolimus, or deforolimus).
  • Patients within 28 days post major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry.
  • Patients who had radiation therapy within 28 days prior to start of study treatment (palliative radiotherapy to bone lesions allowed if completed 2 weeks prior to study treatment start).

Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within 6 months prior to enrollment.

  • Patients with a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrollment.
  • Patients with proteinuria on screening urinalysis confirmed to be >1g /24h by 24 hour urine collection.
  • Patients with inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy.

Patients receiving chronic systemic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable.

  • Patients with a known history of HIV seropositivity.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: unstable angina pectoris (at any time), symptomatic congestive heart failure (NYHA II, III, IV) (at any time), serious uncontrolled cardiac arrhythmia (at any time), myocardial infarction or cerebrovascular accidents ≤ 6 months prior to first study treatment or history of left ventricular dysfunction

    • symptomatic intrinsic lung disease requiring oxygen supplementation at baseline
    • poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN
    • any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
    • liver disease such as cirrhosis or decompensated liver disease.
  • Patients who have a history of another primary malignancy and are off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix.
  • Female patients who are pregnant or breast feeding
  • Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.
  • Patients who have received attenuated live vaccines within one week of study entry. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01399918

Contacts
Contact: Ana M. Molina, MD 646-422-4313
Contact: Martin Voss, MD 646-422-4631

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ana M. Molina, MD    646-422-4313      
Contact: Martin Voss, MD    646-422-4631      
Principal Investigator: Ana M. Molina, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Novartis Pharmaceuticals
Investigators
Principal Investigator: Ana M. Molina, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01399918     History of Changes
Other Study ID Numbers: 10-226
Study First Received: July 20, 2011
Last Updated: March 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Kidney
Everolimus
Bevacizumab
10-226
non-clear cell histology
Advanced

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
Everolimus
Sirolimus
Bevacizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014