Bladder CancerPhase 2NCT00805129
Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium
A Phase 2 study testing Everolimus in people with Bladder Cancer and Metastatic Transitional Cell Carcinoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to learn what effects, good and/or bad, Everolimus has on advanced urothelial cancer. The goal of this clinical research study is to learn if the study drug Everolimus can shrink or slow the growth of urothelial cancer. The safety of this drug will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Metastatic Transitional Cell Carcinoma
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2008to 15 Dec 2021
- 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
- Patients must have a diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis, with histological confirmation at MSKCC.
- Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging.
- Patients must have at least one measurable site of disease (according to RECIST criteria) that has not been previously irradiated.
- Patients must have been previously treated, as defined by the following:
- Treatment with at least one prior cytotoxic agent but not more than four prior cytotoxic agents. Up to four prior chemotherapy agents are allowed, since conventional chemotherapy ranges from just one drug (e.g., gemcitabine) to regimens that contain four agents (e.g., M-VAC is a four-drug regimen containing methotrexate, vinblastine, doxorubicin, and cisplatin).
- The prior therapy must have included at least one of the following: cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine.
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- The prior cytotoxic agents may have been administered in the perioperative or metastatic setting and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or as part of a single regimen.
- Patients must have pre-treatment tumor tissue available for analysis of m-TOR pathway markers. One paraffin block or 10 freshly-prepared unstained slides (on positively charged slides for immunohistochemistry) from the most representative single paraffin-embedded tumor tissue block. Slides from the primary tumor are preferred. If both the primary and metastatic tumor blocks are available, 10 slides from each of the sites should be submitted. If tissue from the primary tumor is not available, a paraffin block or unstained slides from a metastatic site are acceptable. Fine needle aspirates (FNAs) have insufficient tumor tissue and are not permitted.
- Age ≥ 18 years
- Karnofsky Performance Status ≥ 60%
- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL
- Adequate liver function as shown by:
- serum bilirubin ≤ 1.5 x ULN
- INR < 1.3 (or < 3 on anticoagulants)
- ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)
- Adequate renal function: serum creatinine ≤ 1.5 x ULN
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: If a patient's lipid values exceed either one of these criteria upon screening, the patient can only become eligible after successful initiation of appropriate lipid-lowering medication. After lipid-lowering therapy, patients must meet the same criteria - i.e. a fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN - to be eligible for study treatment
- Signed informed consent.
- Testing for hepatitis B viral load and serological markers (HBV-DNA, HBsAg, HBsAb, and HBcAb) for the following patients:
- All patients who currently live in (or have lived in) Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, or Greece
- Patients with any of the following risk factors:
- Known or suspected past hepatitis B infection Blood transfusion(s) prior to 1990
- Current or prior IV drug users
- Current or prior dialysis
- Household contact with hepatitis B infected person(s)
- Current or prior high-risk sexual activity
- Body piercing or tattoos
- Mother known to have hepatitis B History suggestive of hepatitis B infection, e.g dark urine, jaundice, or right upper quadrant pain
- Additional patients at the discretion of the investigator
- Testing for hepatitis C infection (using quantitative RNA-PCR) for patients with any of the following risk factors:
- Known or suspected past hepatitis C infection (including patients with past interferon "curative" treatment)
- Blood transfusion(s) prior to 1990
- Current or prior IV drug users
- Household contact of hepatitis C infected person(s)
- Current or prior high-risk sexual activity
- Body piercing or tattoos
- Additional patients at the discretion of the investigator
Who cannot join
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
- Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients who may require major surgery during the course of the study.
- Prior treatment with any investigational drug within the preceding 4 weeks.
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. Patients receiving these corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with Everolimus. Topical or inhaled corticosteroids are allowed.
- 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.
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- Evidence of another active cancer, except for non-melanoma skin carcinoma, in-situ carcinoma of the cervix curatively treated, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York Heart Association Class III or IV.
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease.
- Severely impaired lung function as evidenced by:
- (TLC) <50% predicted, OR (FVC) <50% predicted OR, (DLCO) <40% predicted
- Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN.
- Active (acute or chronic) or uncontrolled severe infections.
- Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis.
- A known history of HIV seropositivity.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Patients with an active, bleeding diathesis.
- Female patients who are pregnant or breast-feeding, Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of Everolimus.
- Adults of reproductive potential who are not using effective birth control methods. Men and women of childbearing potential must be willing to use effective barrier method contraception during the trial and for at least three months thereafter. Patients are encouraged to continue barrier -method contraception for two years or longer after treatment. Hormonal contraceptives are not acceptable as a sole method of contraception
- Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
- Patients with a known hypersensitivity to Everolimus (RAD001) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
- History of noncompliance to medical regimens.
- Patients unwilling to or unable to comply with the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Study of Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium
The purpose of this study is to learn what effects, good and/or bad, Everolimus has on advanced urothelial cancer.
The goal of this clinical research study is to learn if the study drug Everolimus can shrink or slow the growth of urothelial cancer. The safety of this drug will also be studied. The patients physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Everolimus is safe and effective.
- Being tested
- Everolimus
- Keywords
- URETER, URINARY BLADDER, RAD001, Everolimus, Urothelium, 08-123
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Everolimus will be administered at a dose of 10 mg orally once daily continuously. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Were Progression Free at 2 Months
To measure the two-month PFS rate of Everolimus (RAD001) as determined by RECIST. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: 2 months
Number of Participants Evaluated for Toxicity
To determine the safety and toxicity of Everolimus (RAD001) in this patient population with toxicities being evaluated by CTCAE v3.0
Measured: through study completion, up to 25 months
Secondary outcomes (2)
Response Rate
To determine the response rate of Everolimus in patients with progressive urothelial cancer who have received prior cytotoxic chemotherapy using the Response Evaluation Criteria in Solid Tumors (version 1.0). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: through study completion, up to 25 months
Proportion of Pretreatment Primary Tumor Samples With mTOR Pathway Markers
To assess markers for activated mTOR pathway (including phospho-S6 and phospho-4E BP1) in all pre-treatment tissue specimens and correlate with response to treatment and PFS.
Measured: 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2008 (estimated)
- Study start5 Dec 2008
- Primary completion15 Dec 2021
- Study completion15 Dec 2021
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies 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
- 46 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
- Dean Bajorin, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00805129
- Sponsor's protocol ID
- 08-123
- Status last verified
- Dec 2021
- First submitted
- 8 Dec 2008
- Last updated
- 25 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Milowsky MI, Iyer G, Regazzi AM, Al-Ahmadie H, Gerst SR, Ostrovnaya I, Gellert LL, Kaplan R, Garcia-Grossman IR, Pendse D, Balar AV, Flaherty AM, Trout A, Solit DB, Bajorin DF. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 2013 Aug;112(4):462-70. doi: 10.1111/j.1464-410X.2012.11720.x. Epub 2013 Apr 3.
PubMed 23551593Iyer G, Hanrahan AJ, Milowsky MI, Al-Ahmadie H, Scott SN, Janakiraman M, Pirun M, Sander C, Socci ND, Ostrovnaya I, Viale A, Heguy A, Peng L, Chan TA, Bochner B, Bajorin DF, Berger MF, Taylor BS, Solit DB. Genome sequencing identifies a basis for everolimus sensitivity. Science. 2012 Oct 12;338(6104):221. doi: 10.1126/science.1226344. Epub 2012 Aug 23.
PubMed 22923433
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium
- ClinicalTrials.gov ID
- NCT00805129
- Acronym / sponsor ID
- 08-123
- Keywords
- URETER, URINARY BLADDER, RAD001, Everolimus, Urothelium, 08-123
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 5 Dec 2008 (actual)
- Primary completion
- 15 Dec 2021 (actual)
- Study completion
- 15 Dec 2021 (actual)
- First posted
- 9 Dec 2008 (estimated)
- Results
- Posted 25 Nov 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 learn what effects, good and/or bad, Everolimus has on advanced urothelial cancer.
The goal of this clinical research study is to learn if the study drug Everolimus can shrink or slow the growth of urothelial cancer. The safety of this drug will also be studied. The patients physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Everolimus is safe and effective.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: EverolimusEverolimus will be administered at a dose of 10 mg orally once daily continuously. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Patients must have a diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis, with histological confirmation at MSKCC.
- Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging.
- Patients must have at least one measurable site of disease (according to RECIST criteria) that has not been previously irradiated.
- Patients must have been previously treated, as defined by the following:
- Treatment with at least one prior cytotoxic agent but not more than four prior cytotoxic agents. Up to four prior chemotherapy agents are allowed, since conventional chemotherapy ranges from just one drug (e.g., gemcitabine) to regimens that contain four agents (e.g., M-VAC is a four-drug regimen containing methotrexate, vinblastine, doxorubicin, and cisplatin).
Key exclusion criteria (24 listed)
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
- Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients who may require major surgery during the course of the study.
- Prior treatment with any investigational drug within the preceding 4 weeks.
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. Patients receiving these corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with Everolimus. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
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 |
|---|---|---|
| EverolimusEverolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal. | Drug | Everolimus |
Primary outcome
Number of Participants Who Were Progression Free at 2 Months
Time frame: 2 months
To measure the two-month PFS rate of Everolimus (RAD001) as determined by RECIST. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Number of Participants Evaluated for Toxicity
Time frame: through study completion, up to 25 months
To determine the safety and toxicity of Everolimus (RAD001) in this patient population with toxicities being evaluated by CTCAE v3.0
2 secondary outcomes
Response Rate
Time frame: through study completion, up to 25 months
Proportion of Pretreatment Primary Tumor Samples With mTOR Pathway Markers
Time frame: 25 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23551593Milowsky MI, Iyer G, Regazzi AM, Al-Ahmadie H, Gerst SR, Ostrovnaya I, Gellert LL, Kaplan R, Garcia-Grossman IR, Pendse D, Balar AV, Flaherty AM, Trout A, Solit DB, Bajorin DF. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 2013 Aug;112(4):462-70. doi: 10.1111/j.1464-410X.2012.11720.x. Epub 2013 Apr 3.
- Derived from this study: PubMed 22923433Iyer G, Hanrahan AJ, Milowsky MI, Al-Ahmadie H, Scott SN, Janakiraman M, Pirun M, Sander C, Socci ND, Ostrovnaya I, Viale A, Heguy A, Peng L, Chan TA, Bochner B, Bajorin DF, Berger MF, Taylor BS, Solit DB. Genome sequencing identifies a basis for everolimus sensitivity. Science. 2012 Oct 12;338(6104):221. doi: 10.1126/science.1226344. Epub 2012 Aug 23.
- 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.
Dean Bajorin, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site 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 in people with Bladder Cancer and Metastatic Transitional Cell Carcinoma, run by Memorial Sloan Kettering Cancer Center at 1 site 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 37 inclusion and 24 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 25 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 25 Nov 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?
Number of Participants Who Were Progression Free at 2 Months (time frame: 2 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00805129, which also lists 2 linked publications.
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 25 Nov 2022.