Bladder CancerPhase 1/2NCT01259063
RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder
A Phase 1/2 study testing Everolimus and Intravesical Gemcitabine in people with Bladder Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to test the safety of gemcitabine applied to the bladder directly combined with different oral doses of everolimus and to assess the right doses. Gemcitabine will be given at a fixed dose. Up to 3 dose levels of everolimus will be evaluated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Everolimus and Intravesical Gemcitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Jun 2017
- Phase
- Phase 1/2
- 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 Bacille Calmette-Guérin (BCG) refractory primary or secondary TisN0M0 BCG-refractory disease is defined as:
- Patient positive for Cis after 2 consecutive BCG installations
- OR, patient had a BCG response and failure within 6 months
- OR, patient has Cis on maintenance BCG
- OR, patient has persistent Cis 6 months after at least one instillation of BCG
- OR, patient is BCG intolerant
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- OR, any of the above criteria for patients with a history of T1 disease
- OR, patient has BCG-relapsing disease, defined as failure more than 6 months after the patient was disease-free
- Pathologic confirmation of urothelial carcinoma by the enrolling institution
- Karnofsky Performance Status (KPS) ≥ 70%
- Age ≥ 18 years
- 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 (upper limit of normal)
- ALT and AST ≤ 2.5x ULN
- International normalized ratio (INR) ≤1.5 x ULN (Anticoagulation is allowed if target INR ≤ 1.5 x ULN on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for >2 weeks
- 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: In case one or both of these thresholds are exceeded, the patient can only be included after 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.
- Pre-treatment tumor tissue (minimum 10 slides) or 1 paraffin-embedded block when available for analysis of m-TOR pathway markers.
- Testing for hepatitis B viral load and serological markers (Hepatitis B PCR quantitative, 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 site Principal 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 site Principal 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.) with the exception of topical anti-neoplastic agents that are not being used to treat malignancy
- 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 or patients that 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. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period
- Other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin or adenocarcinoma of the prostate that has been treated.
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- 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 defined by spirometry and diffusing capacity of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
- uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
- active (acute or chronic) or uncontrolled severe infections including urinary tract 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 (eg, 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 (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of Everolimus.
- Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. High effective contraception methods include combination of any two of the following (a+b or a+c or b+c):
- 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 registration. 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 with a known hypersensitivity to Everolimus 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
- Prior radiation to the pelvis for bladder cancer
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 I/II Study of RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder
The purpose of this study is to test the safety of gemcitabine applied to the bladder directly combined with different oral doses of everolimus and to assess the right doses. Gemcitabine will be given at a fixed dose. Up to 3 dose levels of everolimus will be evaluated. The purpose of the phase II part is to test the combination of gemcitabine applied to the bladder directly combined with different oral doses of everolimus and to study the effects of these two drugs together. The investigators want to find out what effects, good and/or bad, this treatment has on the patient and the cancer.
- Conditions
- Bladder Cancer
- Being tested
- Everolimus and Intravesical Gemcitabine
- Keywords
- GEMCITABINE, RAD001(EVEROLIMUS), urinary, BCG-Refractory, Intravesical, 10-165
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus and Intravesical GemcitabineDrug
Phase I: Everolimus will be adm as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be adm at 10 mg daily the dose determined in Phase I. Pts will receive a dose of 2000 mg of intravesical gemcitabine twice a week (72-96 +8 hours between doses) for 3 weeks for a total of 6 treatments in course 1. After 1 week of rest from intravesical gemcitabine, course 2 will be administered, provided the treating physician notes acceptable pt tolerance. The total number of intravesical instillations will be 12. There will be no dose modifications to gemcitabine; however, pts will be allowed to skip gemcitabine doses if needed, per the treating physician's discretion. Missed or skipped doses of gemcitabine will not be repeated. The pt will receive as many instillations as tolerable up to the maximum of 12 instillations.
| Study group | Role | What they receive |
|---|---|---|
| Pts who failed or relapsed after intravesical BCG | Experimental | Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase .Everolimus will be continued for 12 months in the patients who achieve a CR or a Partial Response. Patients demonstrating a CR (by cystoscopy and cytology) or a Partial Response at their Cycle 12 cystoscopy will be observed with serial cystoscopies every 3 months. Receives: Drug: Everolimus and Intravesical Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I - Dose-limiting Toxicity (DLT)
Everolimus (mg) given in conjunction with intravesical gemcitabine
Measured: 8 weeks
Phase II - Patients Who Are Free of Disease at 1 Year
following start of therapy.
Measured: 1 year
Phase I - Maximum Tolerated Dose (MTD)
of Everolimus given in conjunction with intravesical gemcitabine
Measured: 8 weeks
Secondary outcomes (3)
Complete Response (CR) Rate
Complete Response (CR) is defined as no evidence of disease (by cytology and cystoscopy). Partial Response is defined as negative cystoscopy and positive cytology. Progression is defined as the development of invasion or metastasis. If the participant develops a recurrence, they will be considered having failed treatment. Participants will also be considered having failed treatment if there is no response to treatment after two cycles.
Measured: 1 year
Survival of Patients Treated
With Everolimus in combination with intravesical gemcitabine. Overall survival following start of therapy will be estimated using Kaplan-Meier methods.
Measured: 1 year
Activated mTOR (Mammalian Target of Rapamycin) Pathway Markers as Well as Phosphatase and Tensin Homolog (PTEN) Status and Serine/Threonine Kinase (AKT) Activation Evaluation
In all pre-treatment specimens and analysis of post treatment specimens when available.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionJun 2017
- Study completionJun 2017
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 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, New York University, University of Hawaii
- Responsible party
- Sponsor
- Investigators
- Guido Dalbagni, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01259063
- Sponsor's protocol ID
- 10-165
- Status last verified
- Jun 2017
- First submitted
- 9 Dec 2010
- Last updated
- 13 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder
- ClinicalTrials.gov ID
- NCT01259063
- Acronym / sponsor ID
- 10-165
- Conditions
- Bladder Cancer
- Keywords
- GEMCITABINE, RAD001(EVEROLIMUS), urinary, BCG-Refractory, Intravesical, 10-165
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, New York University, University of Hawaii
- Study start
- Dec 2010 (actual)
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 13 Dec 2010 (estimated)
- Results
- Posted 13 Mar 2018
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 test the safety of gemcitabine applied to the bladder directly combined with different oral doses of everolimus and to assess the right doses. Gemcitabine will be given at a fixed dose. Up to 3 dose levels of everolimus will be evaluated. The purpose of the phase II part is to test the combination of gemcitabine applied to the bladder directly combined with different oral doses of everolimus and to study the effects of these two drugs together. The investigators want to find out what effects, good and/or bad, this treatment has on the patient and the cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pts who failed or relapsed after intravesical BCG | Experimental | Drug: Everolimus and Intravesical GemcitabinePhase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase .Everolimus will be continued for 12 months in the patients who achieve a CR or a Partial Response. Patients demonstrating a CR (by cystoscopy and cytology) or a Partial Response at their Cycle 12 cystoscopy will be observed with serial cystoscopies every 3 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Patients must have Bacille Calmette-Guérin (BCG) refractory primary or secondary TisN0M0 BCG-refractory disease is defined as:
- Patient positive for Cis after 2 consecutive BCG installations
- OR, patient had a BCG response and failure within 6 months
- OR, patient has Cis on maintenance BCG
- OR, patient has persistent Cis 6 months after at least one instillation of BCG
Key exclusion criteria (28 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.) with the exception of topical anti-neoplastic agents that are not being used to treat malignancy
- 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 or patients that 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. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within 1 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 |
|---|---|---|
| Everolimus and Intravesical GemcitabinePhase I: Everolimus will be adm as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be adm at 10 mg daily the dose determined in Phase I. Pts will receive a dose of 2000 mg of intravesical gemcitabine twice a week (72-96 +8 hours between doses) for 3 weeks for a total of 6 treatments in course 1. After 1 week of rest from intravesical gemcitabine, course 2 will be administered, provided the treating physician notes acceptable pt tolerance. The total number of intravesical instillations will be 12. There will be no dose modifications to gemcitabine; however, pts will be allowed to skip gemcitabine doses if needed, per the treating physician's discretion. Missed or skipped doses of gemcitabine will not be repeated. The pt will receive as many instillations as tolerable up to the maximum of 12 instillations. | Drug | Pts who failed or relapsed after intravesical BCG |
Primary outcome
Phase I - Dose-limiting Toxicity (DLT)
Time frame: 8 weeks
Everolimus (mg) given in conjunction with intravesical gemcitabine
Phase II - Patients Who Are Free of Disease at 1 Year
Time frame: 1 year
following start of therapy.
Phase I - Maximum Tolerated Dose (MTD)
Time frame: 8 weeks
of Everolimus given in conjunction with intravesical gemcitabine
3 secondary outcomes
Complete Response (CR) Rate
Time frame: 1 year
Survival of Patients Treated
Time frame: 1 year
Activated mTOR (Mammalian Target of Rapamycin) Pathway Markers as Well as Phosphatase and Tensin Homolog (PTEN) Status and Serine/Threonine Kinase (AKT) Activation Evaluation
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2018.
- 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.
Guido Dalbagni, 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 1/2 study testing Everolimus and Intravesical Gemcitabine in people with Bladder Cancer, 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 40 inclusion and 28 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 13 Mar 2018. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 13 Mar 2018). 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?
Phase I - Dose-limiting Toxicity (DLT) (time frame: 8 weeks). The study lists 3 primary outcomes in all. 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 13 Mar 2018.