Bladder CancerPhase 2NCT05072600
Pembrolizumab Monotherapy Following Tri-modality Treatment for Selected Patients With Muscle-invasive Bladder Cancer
A Phase 2 study testing Pembrolizumab in people with Bladder Cancer and Bladder Neoplasms, run by Peking University First Hospital at 1 site in China.
Trial summary
This is a Phase II, single-arm, study of pembrolizumab as maintenance therapy in muscle-invasive bladder cancer (MIBC) participants who have received maximum TURBT and tri-modality treatment (TMT) and achieved CR. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Bladder Neoplasms, Bladder Tumors
- What is being tested?
- Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteChina
- Study dates
- 7 Dec 2021to 1 Nov 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Male/female participants who are at least 18 years of age on the day of signing informed consent.
- Based on AJCC 8th edition: stage cT2-4N0M0，Urothelial carcinoma >50% and
- Requires definitive local therapy
- Has received maximum TURBT followed by tri-modality therapy
- Achieved CR after tri-modality therapy, the acceptable duration of time between completion of TMT and assessment of CR was 28-90 days.
- Tumor was located at one side of bladder wall.
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- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Have adequate organ function prior to the start of study intervention.
Who cannot join
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b disease are considered to have unresectable disease; Has any distant metastases.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
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- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has had an allogeneic tissue/solid organ transplant.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Shang-Bin Qin, MD, +86 010 83572608, 15801682893@163.com
Zhi-Song He, MD
About this study
Official title: A Pilot Study of Pembrolizumab Monotherapy as Maintenance Therapy in MIBC Patients Who Received Bladder-Preserving Trimodally Therapy and Achieved CR
This is a Phase II, single-arm, study of pembrolizumab as maintenance therapy in muscle-invasive bladder cancer (MIBC) participants who have received maximum TURBT and tri-modality treatment (TMT) and achieved CR. All participants will receive pembrolizumab monotherapy per 21 days no longer than 17 cycles until disease progression or death.
Read the detailed description
Radical cystectomy (RC) has long been the standard of care for the treatment of muscle-invasive bladder cancer (MIBC). Modern RC series have demonstrated 5-yr overall survival (OS) rates of 56-66%. There has been an increasing trend of utilizing organ-preserving therapies in the management of bladder cancer over the past several decades. A multidisciplinary approach has led to the development of bladder-sparing approaches using maximal transurethral resection (TURBT) followed by radiotherapy with concomitant radio-sensitizing chemotherapy for MIBC. Multiple tri-modality treatment (TMT) series have suggested that TMT can yield favorable results in well-selected patients. The 5-yr OS is 48-75%, and 75-80% of the survivors have preserved their native bladder. Even if local recurrence occurred after concurrent radio-chemotherapy, salvage cystectomy can also bring 50-57.6% of 5-year disease-specific survival (DSS) without more complications associated with surgery. So, NCCN guidelines have regarded this TMT strategy as a preferred choice for patients with MIBC since 2019.
However, distant metastasis after TMT was still the main concern. Giacalone NJ, et al. reported that the 5-yr distant metastasis rate was 32% in MIBC patients who received an organ-preserving strategy. Up to now, there was no consensus on adjuvant therapy after concurrent radio-chemotherapy. Some retrospective studies demonstrated that adjuvant chemotherapy had no survival benefit, and only approximately 50% of patients completed the planned adjuvant chemotherapy due to intolerable toxicities.
These years, studies on PD-(L)1 inhibitors for urothelial carcinoma showed the efficacy and safety. FDA has approved indications of pembrolizumab used as 1L (selected patients) and 2L treatment for metastatic urothelial carcinoma. Checkmate-274 has reported that adjuvant immunotherapy improved disease-free survival (DFS) in MIBC patients after RC. Javelin Bladder 100 prolonged OS of mUC patients by Avelumab as maintenance therapy who achieved CR, PR or PD after 1L chemotherapy. These results support our hypothesis that, for those MIBC patients who have received bladder-preserving TMT and achieved CR, pembrolizumab monotherapy as maintenance therapy is superior to observation.
- Conditions
- Bladder Cancer, Bladder Neoplasms, Bladder Tumors, Urinary Bladder Cancer, Neoplasms, Bladder
- Being tested
- Pembrolizumab
- Keywords
- bladder cancer, radiotherapy, Pembrolizumab, tri-modality therapy
- 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.
PembrolizumabDrug
Also called PD-1 inhibitor
pembrolizumab 200 mg Q3W
| Study group | Role | What they receive |
|---|---|---|
| arm 1 | Experimental | All participants will receive pembrolizumab monotherapy per 21 days no longer than 17 cycles until disease progression or death. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
PFS is defined as the time from first dose of pembrolizumab to any of the following events: recurrent MIBC, nodal or distant metastases or death due to any cause.
Measured: three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2021
- Study start7 Dec 2021
- Primary completion7 Dec 2024 (estimated)
- Study completion1 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Peking University First HospitalThe 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
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University First Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhisong HE, Peking University First Hospital
- Investigators
- Zhi-Song He, MD, Principal investigator, Peking University First Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05072600
- Sponsor's protocol ID
- 2021-305
- Status last verified
- Dec 2021
- First submitted
- 18 Sep 2021
- Last updated
- 10 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Pembrolizumab Monotherapy as Maintenance Therapy in MIBC Patients Who Received Bladder-Preserving Trimodally Therapy and Achieved CR
- ClinicalTrials.gov ID
- NCT05072600
- Acronym / sponsor ID
- 2021-305
- Conditions
- Bladder Cancer, Bladder Neoplasms, Bladder Tumors, Urinary Bladder Cancer, Neoplasms, Bladder
- Keywords
- bladder cancer, radiotherapy, Pembrolizumab, tri-modality therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Peking University First HospitalUniversity, hospital or other
- Study start
- 7 Dec 2021 (actual)
- Primary completion
- 7 Dec 2024 (estimated)
- Study completion
- 1 Nov 2029 (estimated)
- First posted
- 11 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II, single-arm, study of pembrolizumab as maintenance therapy in muscle-invasive bladder cancer (MIBC) participants who have received maximum TURBT and tri-modality treatment (TMT) and achieved CR. All participants will receive pembrolizumab monotherapy per 21 days no longer than 17 cycles until disease progression or death.
Detailed description
Radical cystectomy (RC) has long been the standard of care for the treatment of muscle-invasive bladder cancer (MIBC). Modern RC series have demonstrated 5-yr overall survival (OS) rates of 56-66%. There has been an increasing trend of utilizing organ-preserving therapies in the management of bladder cancer over the past several decades. A multidisciplinary approach has led to the development of bladder-sparing approaches using maximal transurethral resection (TURBT) followed by radiotherapy with concomitant radio-sensitizing chemotherapy for MIBC. Multiple tri-modality treatment (TMT) series have suggested that TMT can yield favorable results in well-selected patients. The 5-yr OS is 48-75%, and 75-80% of the survivors have preserved their native bladder. Even if local recurrence occurred after concurrent radio-chemotherapy, salvage cystectomy can also bring 50-57.6% of 5-year disease-specific survival (DSS) without more complications associated with surgery. So, NCCN guidelines have regarded this TMT strategy as a preferred choice for patients with MIBC since 2019.
However, distant metastasis after TMT was still the main concern. Giacalone NJ, et al. reported that the 5-yr distant metastasis rate was 32% in MIBC patients who received an organ-preserving strategy. Up to now, there was no consensus on adjuvant therapy after concurrent radio-chemotherapy. Some retrospective studies demonstrated that adjuvant chemotherapy had no survival benefit, and only approximately 50% of patients completed the planned adjuvant chemotherapy due to intolerable toxicities.
These years, studies on PD-(L)1 inhibitors for urothelial carcinoma showed the efficacy and safety. FDA has approved indications of pembrolizumab used as 1L (selected patients) and 2L treatment for metastatic urothelial carcinoma. Checkmate-274 has reported that adjuvant immunotherapy improved disease-free survival (DFS) in MIBC patients after RC. Javelin Bladder 100 prolonged OS of mUC patients by Avelumab as maintenance therapy who achieved CR, PR or PD after 1L chemotherapy. These results support our hypothesis that, for those MIBC patients who have received bladder-preserving TMT and achieved CR, pembrolizumab monotherapy as maintenance therapy is superior to observation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| arm 1 | Experimental | Drug: PembrolizumabAll participants will receive pembrolizumab monotherapy per 21 days no longer than 17 cycles until disease progression or death. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male/female participants who are at least 18 years of age on the day of signing informed consent.
- Based on AJCC 8th edition: stage cT2-4N0M0，Urothelial carcinoma >50% and
- Tumor was located at one side of bladder wall.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Key exclusion criteria (19 listed)
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b disease are considered to have unresectable disease; Has any distant metastases.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
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: PD-1 inhibitorpembrolizumab 200 mg Q3W | Drug | arm 1 |
Primary outcome
PFS
Time frame: three years
PFS is defined as the time from first dose of pembrolizumab to any of the following events: recurrent MIBC, nodal or distant metastases or death due to any cause.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2022.
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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.
Zhi-Song He, MD principal investigator
Peking University First Hospital
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 Bladder Cancer and Bladder Neoplasms, run by Peking University First Hospital at 1 site in China.
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 10 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 10 Jan 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 China. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shang-Bin Qin, MD (+86 010 83572608, 15801682893@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: three years). 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 10 Jan 2022.