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

NCT01399918 | Completed Phase 2 Results

• 1 other identifier: 10-226
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Renal Cell Carcinoma

Keywords

Kidney; Everolimus; Bevacizumab; 10-226; non-clear cell histology; Advanced

Outcome Measures

Primary Outcomes (1)

• To Evaluate the Efficacy of Combining Everolimus and Bevacizumab in Patients With Advanced RCC of Non-clear Cell Histology

  the percent of patients alive and progression-free after 6 months of therapy.

  6 months

Secondary Outcomes (2)

• Secondary Endpoint Will be the Overall Response Rate (ORR)

  1 year

• Participants Evaluated for Toxicity

  2 years

Study Arms (1)

everolimus and bevacizumab

EXPERIMENTAL

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. A separate cohort of patients with non-clear cell RCC with papillary features will be enrolled in order to gather information regarding the efficacy given the rarity of these entities.

Drug: everolimus and bevacizumab

Interventions

everolimus and bevacizumab DRUG

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.

everolimus and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤2.0 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 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 %.
• 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.

You may not qualify if:

• 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 without complications require 48 hours 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 III, IV) (at any time), serious uncontrolled cardiac arrhythmia (at any time), myocardial infarction, cerebrovascular accidents, or symptomatic left ventricular dysfunction ≤ 6 months prior to first study treatment
• active bleeding diathesis
• known severely impaired lung function defined as spirometry and DLCO ≤ 50% of normal and oxygen saturation at rest ≤ 88% on room air.
• symptomatic intrinsic lung disease requiring oxygen supplementation at baseline
• Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, 07939, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Everolimus; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Darren Feldman
• Organization: Memorial Sloan Kettering Cancer Center

Feldmand@MSKCC.ORG

646-888-4740

Study Officials

• Darren Feldman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2011
• First Posted: July 22, 2011
• Study Start: July 1, 2011
• Primary Completion: December 28, 2020
• Study Completion: December 28, 2020
• Last Updated: February 1, 2022
• Results First Posted: February 1, 2022

Record last verified: 2020-12

Locations

US (7)