Stage I Bladder Cancer AJCC v8Phase 2NCT03319745
Pembrolizumab in Treating Patients With Bladder Cancer Undergoing Radical Cystectomy
A Phase 2 study testing Pembrolizumab in people with Stage I Bladder Cancer AJCC v8 and Stage II Bladder Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies the side effects of pembrolizumab and to see how well it works in treating patients with bladder cancer who are undergoing surgery to remove the bladder. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage I Bladder Cancer AJCC v8, Stage II Bladder Cancer AJCC v8, Stage III Bladder Cancer AJCC v8
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jan 2018to 1 May 2023
- 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
- Be willing and able to provide written informed consent.
- Have absence of metastatic disease as determined by conventional imaging studies and be considered a good surgical candidate by the treating physician.
- Be willing to participate in the collection of blood and tissue for banking and future correlative studies.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
- Absolute neutrophil count (ANC) >= 1,500 /mcL.
- Platelets >= 100,000/mcL.
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- Hemoglobin (Hgb) >= 9 g/dL or >= 5.6 mmol/L without (w/o) transfusion within 7 days of assessment.
- Creatinine OR calculated creatinine clearance =< 1.5 x upper limit of normal (ULN) OR >= 30 mL/min for subject with creatinine levels > 1.5 x institutional ULN. Creatinine clearance should be calculated per institutional standard.
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases.
- Albumin > 2.5 mg/dL.
- Coagulation international normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Who cannot join
- Is currently participating and receiving pembrolizumab or has participated in a study of an investigational agent and received pembrolizumab or used an investigational device within 4 weeks of the first dose of study treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Has a known history of active TB (Bacillus tuberculosis).
- Has a known history of hypersensitivity to pembrolizumab or any of its excipients.
- Has had prior systemic anti-cancer therapy for the treatment of bladder cancer. Prior intravesical therapies, whether Bacillus Calmette-Guerin (BCG) (including but not limited to: persistent high-grade disease or recurrence within 6 months of receiving at least two courses of intravesical BCG [at least five of six induction doses and at least two of three maintenance doses]; or T1 high-grade disease at the first evaluation following induction BCG alone [at least five of six induction doses]), chemotherapy or otherwise, will remain eligible.
- Has any other malignancy diagnosed within 2 years of screening with the exception of basal or squamous cell skin cancer, or non-invasive cancer of the cervix, or any other cancer deemed by the treating physician to be of low-risk for progression or patient morbidity during the study period.
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- Has known metastatic disease as determined by conventional staging studies.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has a clinically significant active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
- Has received a live vaccine within 30 days of initiation of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Window of Opportunity Phase II Study of Pembrolizumab in Patients With Bladder Cancer Undergoing Radical Cystectomy
This phase II trial studies the side effects of pembrolizumab and to see how well it works in treating patients with bladder cancer who are undergoing surgery to remove the bladder. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Read the detailed description
PRIMARY OBJECTIVE:
- To characterize the safety profile of pembrolizumab in patients with urothelial carcinoma undergoing radical cystectomy.
SECONDARY OBJECTIVES:
- To explore a signal of anti-cancer immunological activity by evaluating surgical specimens for evidence of post-treatment lymphocytic infiltration and residual tumor compared to pre-treatment biopsy samples.
II. To explore a signal of biomarker activity by evaluating surgical specimens and blood samples for established and not-so-established markers of response to pembrolizumab.
III. To report the tumor yield and sufficiency of tumor for immunological and biomarker activity.
IV. To examine the interaction of the human microbiome and pathologic response to pembrolizumab.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. About 4 weeks after treatment, patients then undergo radical cystectomy per standard of care.
After completion of study treatment, patients are followed up to 30 and 90 days.
- Conditions
- Stage I Bladder Cancer AJCC v8, Stage II Bladder Cancer AJCC v8, Stage III Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8, Stage IIIB Bladder Cancer AJCC v8
- Being tested
- Pembrolizumab
- 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.
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab) | Experimental | Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. About 4 weeks after treatment, patients then undergo radical cystectomy per standard of care. Receives: Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity for Safety Monitoring (TOX)
The primary endpoint is a joint endpoint classifying patients as having a toxicity of concern (TOX), defined as the presence of any of these: 1) any 30-day grade 3 or higher surgical complication at least possibly related to the treatment, 2) any toxicity at least possibly related to the treatment that prevents surgery, or 3) death between the start of the study and the 30-day post-surgical assessment as long as it is at least possibly related to pembrolizumab or surgery.
Measured: From initiation of pembrolizumab, until 90 days post-surgery, up to a maximum of 5.5 months
Secondary outcomes (1)
Efficacy Endpoint
To explore anti-cancer immunological activity by evaluating surgical specimens for evidence of post-treatment and residual tumor compared to pre-treatment biopsy samples. The main mechanism for doing so will be via histopathologic review of the radical cystectomy specimen. MIBC participants are defined as responders if they achieve a pT1 stage or less. In the case of NMIBC a pT0 status will be used to identify complete response.
Measured: Efficacy endpoint will be measured at time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study start11 Jan 2018
- Primary completion1 May 2023
- Study completion1 May 2023
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 Stage I Bladder Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by M.D. Anderson 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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Neema Navai, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03319745
- Sponsor's protocol ID
- 2017-0057
- Other IDs
- NCI-2018-01032, 2017-0057
- Status last verified
- Jun 2024
- First submitted
- 20 Oct 2017
- Last updated
- 25 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Window of Opportunity Phase II Study of Pembrolizumab in Patients With Bladder Cancer Undergoing Radical Cystectomy
- ClinicalTrials.gov ID
- NCT03319745
- Acronym / sponsor ID
- 2017-0057
- Conditions
- Stage I Bladder Cancer AJCC v8, Stage II Bladder Cancer AJCC v8, Stage III Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8, Stage IIIB Bladder Cancer AJCC v8
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 11 Jan 2018 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 1 May 2023 (actual)
- First posted
- 24 Oct 2017 (actual)
- Results
- Posted 25 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies the side effects of pembrolizumab and to see how well it works in treating patients with bladder cancer who are undergoing surgery to remove the bladder. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVE:
- To characterize the safety profile of pembrolizumab in patients with urothelial carcinoma undergoing radical cystectomy.
SECONDARY OBJECTIVES:
- To explore a signal of anti-cancer immunological activity by evaluating surgical specimens for evidence of post-treatment lymphocytic infiltration and residual tumor compared to pre-treatment biopsy samples.
II. To explore a signal of biomarker activity by evaluating surgical specimens and blood samples for established and not-so-established markers of response to pembrolizumab.
III. To report the tumor yield and sufficiency of tumor for immunological and biomarker activity.
IV. To examine the interaction of the human microbiome and pathologic response to pembrolizumab.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. About 4 weeks after treatment, patients then undergo radical cystectomy per standard of care.
After completion of study treatment, patients are followed up to 30 and 90 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pembrolizumab) | Experimental | Biological: PembrolizumabPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. About 4 weeks after treatment, patients then undergo radical cystectomy per standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Be willing and able to provide written informed consent.
- Have absence of metastatic disease as determined by conventional imaging studies and be considered a good surgical candidate by the treating physician.
- Be willing to participate in the collection of blood and tissue for banking and future correlative studies.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
- Absolute neutrophil count (ANC) >= 1,500 /mcL.
Key exclusion criteria (16 listed)
- Is currently participating and receiving pembrolizumab or has participated in a study of an investigational agent and received pembrolizumab or used an investigational device within 4 weeks of the first dose of study treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Has a known history of active TB (Bacillus tuberculosis).
- Has a known history of hypersensitivity to pembrolizumab or any of its excipients.
- Has had prior systemic anti-cancer therapy for the treatment of bladder cancer. Prior intravesical therapies, whether Bacillus Calmette-Guerin (BCG) (including but not limited to: persistent high-grade disease or recurrence within 6 months of receiving at least two courses of intravesical BCG [at least five of six induction doses and at least two of three maintenance doses]; or T1 high-grade disease at the first evaluation following induction BCG alone [at least five of six induction doses]), chemotherapy or otherwise, will remain eligible.
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (pembrolizumab) |
Primary outcome
Toxicity for Safety Monitoring (TOX)
Time frame: From initiation of pembrolizumab, until 90 days post-surgery, up to a maximum of 5.5 months
The primary endpoint is a joint endpoint classifying patients as having a toxicity of concern (TOX), defined as the presence of any of these: 1) any 30-day grade 3 or higher surgical complication at least possibly related to the treatment, 2) any toxicity at least possibly related to the treatment that prevents surgery, or 3) death between the start of the study and the 30-day post-surgical assessment as long as it is at least possibly related to pembrolizumab or surgery.
1 secondary outcome
Efficacy Endpoint
Time frame: Efficacy endpoint will be measured at time of surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Testing the Addition of an Anti-cancer Drug, Pembrolizumab, to the Usual Intravesical Chemotherapy Treatment (Gemcitabine) for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer
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RecruitingPhase 2
Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to Radiation Therapy Compared to the Usual Chemotherapy Treatment During Radiation Therapy for Bladder Cancer, PARRC Trial
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RecruitingPhase 1/2
In-home Intravesical Chemotherapy for the Treatment of Bladder Cancer, INVITE Trial
Non-Muscle Invasive Bladder Carcinoma, Stage 0a Bladder Cancer AJCC v8
RecruitingPhase 3
Testing the Addition of an Anti-Cancer Drug, Gemcitabine, to Usual Treatment (BCG Alone) in People Whose Non-Muscle Invasive Bladder Cancer (NMIBC) Came Back After Prior BCG Therapy
Recurrent Non-Muscle Invasive Bladder Carcinoma, Stage 0a Bladder Cancer AJCC v8
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.
Neema Navai principal investigator
M.D. Anderson 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 Pembrolizumab in people with Stage I Bladder Cancer AJCC v8 and Stage II Bladder Cancer AJCC v8, run by M.D. Anderson 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 15 inclusion and 16 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 Jun 2024. 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 Jun 2024). 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?
Toxicity for Safety Monitoring (TOX) (time frame: From initiation of pembrolizumab, until 90 days post-surgery, up to a maximum of 5.5 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 25 Jun 2024.