Metastatic Transitional Cell Carcinoma of the UrotheliumPhase 2NCT01551030
Buparlisib in Metastatic Transitional Cell Carcinoma of the Urothelium
A Phase 2 study testing Buparlisib in people with Metastatic Transitional Cell Carcinoma of the Urothelium, run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.
Trial summary
The purpose of this study is to learn what effects, good and/or bad, Buparlisib has on advanced urothelial cancer. Buparlisib is a pill that works by shutting down some of the signals in cancer cells that make tumors grow. It is being tested in patients in research studies such as this one. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Transitional Cell Carcinoma of the Urothelium
- What is being tested?
- Buparlisib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2012to 2 Sep 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
- Age ≥ 18 years
- Karnofsky Performance Status (KPS) ≥60%
- Urothelial carcinoma of the bladder, urethra, ureter or renal pelvis, with histologic confirmation at MSKCC. Patients with unresected primary tumors may be enrolled as long as evidence of metastatic disease is also present.
- Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging (RECIST Version 1.1).
- Patients must have been previously treated, as defined by the following:
- Patients must have received treatment with at least one prior cytotoxic chemotherapy agent but not more than four prior cytotoxic chemotherapy agents for urothelial carcinoma. 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).
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- The prior therapy must have consisted of at least one of the following: cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine.
- o 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 at least one site of measurable disease per RECIST 1.1 criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
- Patients enrolling in the Phase II study must have pre-treatment tumor tissue available for PI3K/Akt pathway marker analysis: One paraffin block, frozen curls or 10 freshly-prepared unstained slides from the most representative single paraffinembedded tumor tissue block should be submitted. 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.
- Patients enrolling in the Expansion Cohort must have prior mutational testing demonstrating alterations within the PI3K/Akt/mTOR pathway predicted to result in pathway activation.
- Life expectancy of ≥ 12 weeks
- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L,
- Hemoglobin >9 g/dL
- Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed)
- Corrected Calcium = (0.8 * (Normal Albumin - Pt's Albumin)) + Serum Ca
- Potassium and magnesium within normal limits
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range [or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present]
- Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with welldocumented Gilbert syndrome)
- Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
- INR ≤ 2
- Serum amylase and lipase ≤ ULN
- Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
- Ability to swallow oral medication
Who cannot join
- Patients who have received prior treatment with a P13K inhibitor.
- Patients receiving any other investigational therapies.
- Patients with a known hypersensitivity to Buparlisib 120 or to its excipients
- Patients with untreated brain metastases are excluded. However, patients may participate in this trial if > 4 weeks from completion of therapy (radiation and/or surgery) for CNS metastases, are clinically stable at the time of registration and are not receiving corticosteroid therapy
- Patients with acute or chronic hepatic or renal disease or pancreatitis
- Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire:
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- o Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
- ≥ CTCAE grade 3 anxiety
- o Meet the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or select a positive response of "1", "2", or "3" to question number 9 regarding the potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
- Patients with diarrhea ≥ CTCAE grade 2 or other impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Buparlisib120 (e.g., ulcerative diseases, uncontrolled, nausea, vomiting, malabsorption syndrome, or small bowel resection)
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 480 msec on screening ECG (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patients with uncontrolled diabetes mellitus or steroid-induced diabetes mellitus.
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
- Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of lung volumes, DLCO, O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
- Patients who are currently receiving treatment with any medication that has the potential to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug. Refer to Appendix A for a list of prohibited QT-prolonging medications.
- Patients receiving chronic treatment with steroids or another immunosuppressive agent o Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. Patients with previously treated brain metastases who are on stable low dose corticosteroid treatment (e.g., dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible.
- Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug. Herbal medications include, but are not limited to, St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits.
- Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Appendix A for a list of moderate to strong inhibitors of CYP3A4 (Please note that co-treatment with weak inhibitors of CYP3A4 is allowed).
- Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug or whose side effects from chemotherapy or targeted anticancer therapy have not recovered to a grade 1 before starting the trial.
- Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy.
- Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug, patients who have not recovered from side effects of any major surgery, or patients who may require major surgery during the course of the study
- Patients who are currently taking therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulant.
- Women who are pregnant or breast feeding or adults of child-bearing potential not employing an effective method of birth control. Women of child-bearing potential, must have a negative serum pregnancy test ≤ 48 hours prior to initiating treatment. Effective methods of birth control.
- Known diagnosis of human immunodeficiency virus (HIV) infection
- History of another malignancy within 3 years, except non-melanoma skin cancer, excised carcinoma in situ of the cervix or adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable
- Patients who are unwilling or unable to abide by the study protocol or cooperate fully with the investigator
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, 11570
Memoral Sloan Kettering Cancer Center@Phelps
Sleepy Hollow, New York
About this study
Official title: Phase II Study of Buparlisib in Metastatic Transitional Cell Carcinoma of the Urothelium
The purpose of this study is to learn what effects, good and/or bad, Buparlisib has on advanced urothelial cancer. Buparlisib is a pill that works by shutting down some of the signals in cancer cells that make tumors grow. It is being tested in patients in research studies such as this one. As of 2010, more than 80 patients with various types of cancer have received treatment with Buparlisib in research studies.
This clinical research study is divided into two parts. The goal of the first part of this study is to learn if the study drug Buparlisib can shrink or slow the growth of cancer in patients with urothelial tumors. The goal of the second part of this study is to learn if the study drug Buparlisib can shrink or slow the growth of urothelial tumors in patients known to have certain genetic alterations that cause these types of tumors. The study doctor will inform the patient which part of the study is currently enrolling participants. Participants in both parts of the study will receive the same treatment and tests.
The safety of this drug will also be studied in both parts. The physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Buparlisib is safe and effective.
- Being tested
- Buparlisib
- Keywords
- KIDNEY, URETER, URINARY BLADDER, Buparlisib, 11-060
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuparlisibDrug
Buparlisib will be administered at a dose of 100 mg orally once daily (two 50 mg capsules) continuously. Intra-patient dose reduction may be required depending on the type and severity of the individual toxicity encountered. Re-staging imaging studies will be performed after every two cycles of treatment (one cycle = 4 weeks). Patients may continue on study as long as they are tolerating therapy and are free of disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Buparlisib | Experimental | This is an open-label phase II study of the pan-class I selective phosphoinositide 3-kinase (PI3K) inhibitor Buparlisib in patients with metastatic urothelial carcinoma which has progressed despite treatment with prior cytotoxic chemotherapy. Receives: Drug: Buparlisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Progression Free Survival (PFS) at 2 Months
at 2 months for the pan-class I selective PI3K inhibitor Buparlisib in patients with metastatic urothelial cancer that has progressed on prior cytotoxic chemotherapy. Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 2 months
Progression Free Survival (PFS) in the Expansion Cohort
Measured: Up to 16 months
Secondary outcomes (2)
Response Rate
as determined by RECIST v1.1 for Buparlisib in patients with progressive metastatic urothelial cancer who have received prior cytotoxic chemotherapy
Measured: 2 months
Number of Participants Evaluated for Toxicity
To establish the safety and toxicity of Buparlisib , the frequency of toxicity will be tabulated according to the NCI Common Toxicity Criteria, version 4.0.
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 posted12 Mar 2012 (estimated)
- Study startMar 2012
- Primary completion2 Sep 2020
- Study completion2 Sep 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 Metastatic Transitional Cell Carcinoma of the UrotheliumStudies 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Dean Bajorin, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01551030
- Sponsor's protocol ID
- 11-060
- Status last verified
- Sep 2020
- First submitted
- 8 Mar 2012
- Last updated
- 21 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Buparlisib in Metastatic Transitional Cell Carcinoma of the Urothelium
- ClinicalTrials.gov ID
- NCT01551030
- Acronym / sponsor ID
- 11-060
- Keywords
- KIDNEY, URETER, URINARY BLADDER, Buparlisib, 11-060
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Mar 2012 (actual)
- Primary completion
- 2 Sep 2020 (actual)
- Study completion
- 2 Sep 2020 (actual)
- First posted
- 12 Mar 2012 (estimated)
- Results
- Posted 21 Jun 2021
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, Buparlisib has on advanced urothelial cancer. Buparlisib is a pill that works by shutting down some of the signals in cancer cells that make tumors grow. It is being tested in patients in research studies such as this one. As of 2010, more than 80 patients with various types of cancer have received treatment with Buparlisib in research studies.
This clinical research study is divided into two parts. The goal of the first part of this study is to learn if the study drug Buparlisib can shrink or slow the growth of cancer in patients with urothelial tumors. The goal of the second part of this study is to learn if the study drug Buparlisib can shrink or slow the growth of urothelial tumors in patients known to have certain genetic alterations that cause these types of tumors. The study doctor will inform the patient which part of the study is currently enrolling participants. Participants in both parts of the study will receive the same treatment and tests.
The safety of this drug will also be studied in both parts. The physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Buparlisib 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 |
|---|---|---|
| Buparlisib | Experimental | Drug: BuparlisibThis is an open-label phase II study of the pan-class I selective phosphoinositide 3-kinase (PI3K) inhibitor Buparlisib in patients with metastatic urothelial carcinoma which has progressed despite treatment with prior cytotoxic chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Age ≥ 18 years
- Karnofsky Performance Status (KPS) ≥60%
- Urothelial carcinoma of the bladder, urethra, ureter or renal pelvis, with histologic confirmation at MSKCC. Patients with unresected primary tumors may be enrolled as long as evidence of metastatic disease is also present.
- Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging (RECIST Version 1.1).
- Patients must have been previously treated, as defined by the following:
Key exclusion criteria (36 listed)
- Patients who have received prior treatment with a P13K inhibitor.
- Patients receiving any other investigational therapies.
- Patients with a known hypersensitivity to Buparlisib 120 or to its excipients
- Patients with untreated brain metastases are excluded. However, patients may participate in this trial if > 4 weeks from completion of therapy (radiation and/or surgery) for CNS metastases, are clinically stable at the time of registration and are not receiving corticosteroid therapy
- Patients with acute or chronic hepatic or renal disease or pancreatitis
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 |
|---|---|---|
| BuparlisibBuparlisib will be administered at a dose of 100 mg orally once daily (two 50 mg capsules) continuously. Intra-patient dose reduction may be required depending on the type and severity of the individual toxicity encountered. Re-staging imaging studies will be performed after every two cycles of treatment (one cycle = 4 weeks). Patients may continue on study as long as they are tolerating therapy and are free of disease progression. | Drug | Buparlisib |
Primary outcome
Percentage of Participants With Progression Free Survival (PFS) at 2 Months
Time frame: 2 months
at 2 months for the pan-class I selective PI3K inhibitor Buparlisib in patients with metastatic urothelial cancer that has progressed on prior cytotoxic chemotherapy. Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST).
Progression Free Survival (PFS) in the Expansion Cohort
Time frame: Up to 16 months
2 secondary outcomes
Response Rate
Time frame: 2 months
Number of 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 21 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
Related trials for Metastatic Transitional Cell Carcinoma of the Urothelium
Active, not recruitingPhase 1/2
Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction
Advanced Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma
Active, not recruitingPhase 2
Prophylactic Cranial Irradiation (PCI) for Small Cell Carcinoma of the Urothelium
Bladder Cancer
Active, not recruitingPhase 1
Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate
Bladder Small Cell Neuroendocrine Carcinoma, Castration-Resistant Prostate Carcinoma
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
5 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 Buparlisib in people with Metastatic Transitional Cell Carcinoma of the Urothelium, run by Memorial Sloan Kettering Cancer Center at 5 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 24 inclusion and 36 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 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 21 Jun 2021). 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?
Percentage of Participants With Progression Free Survival (PFS) 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?
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 21 Jun 2021.