Renal Cell CarcinomaPhase 2NCT01399918
Everolimus and Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma (RCC)
A Phase 2 study testing everolimus and bevacizumab in people with Renal Cell Carcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- everolimus and bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 7 sitesUnited States
- Study dates
- Jul 2011to 28 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced renal cell carcinoma of non-clear cell histology, histologically with papillary features confirmed by MSKCC pathology. 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
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- 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 %.
- 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.
Who cannot join
- 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.
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- 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
- 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 decompensated liver disease or active and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HBsAg, quantifiable HCV-RNA).
- 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
- Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after. Highly effective contraception methods include combination of any two of the following:
- Use of oral, injected or implanted hormonal methods of contraception or;
- Placement of an intrauterine device (IUD) or intrauterine system (IUS);
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
- Total abstinence or;
- Male/female sterilization
- Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
- Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
- 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. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus).
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus.
- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Memorial Sloan Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Cancer Center at Basking Ridge
Basking Ridge, New Jersey, 07939
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering at Mercy Medical Center
Rockville Centre, New York
About this study
Official title: A Phase II Trial of Everolimus and Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma (RCC)
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
- Being tested
- everolimus and bevacizumab
- Keywords
- Kidney, Everolimus, Bevacizumab, 10-226, non-clear cell histology, Advanced
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimus and bevacizumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: everolimus and bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (2)
Secondary Endpoint Will be the Overall Response Rate (ORR)
per the international criteria defined by the Response Evaluation Criteria in Solid Tumors Committee
Measured: 1 year
Participants Evaluated for Toxicity
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study startJul 2011
- Primary completion28 Dec 2020
- Study completion28 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Darren Feldman, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01399918
- Sponsor's protocol ID
- 10-226
- Status last verified
- Dec 2020
- First submitted
- 20 Jul 2011
- Last updated
- 1 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Everolimus and Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma (RCC)
- ClinicalTrials.gov ID
- NCT01399918
- Acronym / sponsor ID
- 10-226
- Conditions
- Renal Cell Carcinoma
- Keywords
- Kidney, Everolimus, Bevacizumab, 10-226, non-clear cell histology, Advanced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Jul 2011
- Primary completion
- 28 Dec 2020 (actual)
- Study completion
- 28 Dec 2020 (actual)
- First posted
- 22 Jul 2011 (estimated)
- Results
- Posted 1 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| everolimus and bevacizumab | Experimental | Drug: everolimus and bevacizumabThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Advanced renal cell carcinoma of non-clear cell histology, histologically with papillary features confirmed by MSKCC pathology. 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
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimus and bevacizumabCycle 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. | Drug | everolimus and bevacizumab |
Primary outcome
To Evaluate the Efficacy of Combining Everolimus and Bevacizumab in Patients With Advanced RCC of Non-clear Cell Histology
Time frame: 6 months
the percent of patients alive and progression-free after 6 months of therapy.
2 secondary outcomes
Secondary Endpoint Will be the Overall Response Rate (ORR)
Time frame: 1 year
Participants Evaluated for Toxicity
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darren Feldman, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus and bevacizumab in people with Renal Cell Carcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Evaluate the Efficacy of Combining Everolimus and Bevacizumab in Patients With Advanced RCC of Non-clear Cell Histology (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2022.