Bladder CancerPhase 1MARCNCT02324582
MK-3475/BCG in High Risk Superficial Bladder Cancer
A Phase 1 study testing Intravenous MK-3475/ Intravesical BCG in people with Bladder Cancer, run by Southern Illinois University at 3 sites in United States.
Trial summary
This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment for patients, 18 years or older, with high risk superficial bladder cancer (cancer not yet involving the muscle of the bladder wall) who have had removal of their bladder tumor. 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?
- Intravenous MK-3475/ Intravesical BCG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2015to 27 Mar 2023
- Phase
- Phase 1
- 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
- 1.Willing and able to provide written informed consent/assent.
- 2.18 years of age.
- 3.Have pathologically documented high grade transitional cell superficial bladder cancer (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the bladder at time of initial resection for recurrent/persistent high risk transitional cell superficial bladder cancer.
- 4.Recurrent/persistent disease despite 2 Induction Intravesical Therapy Courses given within 12 months (with BCG being one of them), or despite one induction BCG treatment in addition to at least one maintenance course of BCG 5.Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
- 6.ECOG performance status of 0-2. 7.Demonstrate adequate organ function 8.Female subject of childbearing potential should have a negative urine or serum pregnancy.
- 9.Female subjects of childbearing potential should be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication 10.Male subjects should 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.
Who cannot join
- Currently has active or progressive metastatic disease.
- Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of 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 trial treatment.
- Prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for bladder cancer.
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Show all 21Show fewer
- Known additional malignancy that is progressing or requires active treatment.
- Active autoimmune disease that has required systemic treatment in past 2 years.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Active infection, including a concurrent febrile illness, requiring systemic therapy.
- 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 investigator.
- 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 trial, starting with the pre-screening or screening visit through 4 months after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) including anti-CD40 and anti-OX40 antibodies.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBs Ag reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has known active tuberculosis. Subjects will not be specifically tested for the study; however, subjects that are tested within 28 days of beginning study or while on study and test positive with the PPD test before treatment should have active tuberculosis ruled out before therapy begins for their superficial bladder cancer.
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
- Has an active urinary tract infection, gross hematuria, or known broken mucosal barrier of the bladder.
- Less than 14 days post bladder biopsy, TUR, or traumatic catheterization.
- Evidence of muscle invasive bladder cancer, or transitional cell carcinoma of the upper urinary tract
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Henry Ford Health Systems
Detroit, Michigan, 48202
Simmons Cancer Institute-SIU School of Medicine
Springfield, Illinois, 62702
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
About this study
Official title: Phase I Study of MK-3475 in Combination With BCG for Patients With High Risk Superficial Bladder Cancer
This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment for patients, 18 years or older, with high risk superficial bladder cancer (cancer not yet involving the muscle of the bladder wall) who have had removal of their bladder tumor. Patients will be enrolled to a single treatment group of a fixed dose of MK 3475 and BCG.
Read the detailed description
Bladder cancer is the fifth most common cancer in the United States. This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment. The study will determine the safety of administering MK-3475 at a fixed dose every three weeks in conjunction with intravesicular BCG treatment in non-muscle invasive bladder cancer patients who had recurrence after two courses of induction (6 doses) intravesical therapy (two BCG courses, or one BCG course and one other approved intravesical therapies) administered within 12 months, or after one induction (6 doses) and one maintenance (3 doses) intravesical therapy (BCG). Subjects will have confirmation of bladder cancer non-invasive to the muscle. Approximately 20 subjects will be screened to treat 15 eligible subjects with high risk superficial bladder cancer who have had transurethral resection of their bladder tumor.
The rationale for the use of the indicated dose of TICE® BCG is based upon FDA approved and commercially provided package insert/ instructions for use of the product. BCG installation has been used to treat non-muscle-invasive bladder cancer for more than 30 years. It is one of the most successful biotherapies for cancer in use. Despite long clinical experience with BCG, the mechanism of its therapeutic effect is still under investigation.
The first 3 subjects will be treated at a dose of 100 mg MK-3475 to ensure safety for the combination. If no safety or efficacy issues are present, dosing will be escalated to 200 mg MK-3475 every 3 weeks.
- Conditions
- Bladder Cancer
- Being tested
- Intravenous MK-3475/ Intravesical BCG
- Keywords
- Urinary Bladder Neoplasms, Mycobacterium bovis, Programmed Cell Death 1 Receptor, 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.
Intravenous MK-3475/ Intravesical BCGDrug
Also called pembrolizumab
6 cycles (each cycle is 21 days) of pembrolizumab will be given over 9 weeks in combination with BCG. BCG treatment will begin on Day 1 of cycle 3 of pembrolizumab.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous MK-3475/ Intravesical BCG | Experimental | 3 subjects will be treated at a dose of 100 mg MK-3475 at 100 mg every 3 weeks (Q3W) intravenously (IV) for 6 doses and 1 vial intravesicular BCG suspended in 50 ml preservative-free saline once per week of 6 weekly doses 12 subjects will be treated at a dose of 200 mg MK-3475 at 100 mg every 3 weeks (Q3W) intravenously (IV) for 6 doses and 1 vial intravesicular BCG suspended in 50 ml preservative-free saline once per week of 6 weekly doses Receives: Drug: Intravenous MK-3475/ Intravesical BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Grade 3, 4, and 5 Treatment Related Adverse Events
Grade and quantity of treatment related adverse events. Due to the small sampling of subjects, no statistical analysis will be performed. Descriptive statistics in the form of counts calculated as percentages will be reported.
Measured: change from baseline to 23 weeks
Secondary outcomes (1)
Number of Participants Without Bladder Tumors Upon Cystoscopy Following Treatment.
Complete response rate per cystoscopy assessment of the bladder at 19 weeks from start of treatment with MK-3475 (pembrolizumab) at week 1.Subjects presenting at Week 19 with a bladder free of tumors upon cystoscopy and without local or metastatic spread were considered a complete response.. Suspicious lesions would be biopsied and sent for confirmation of pathology. Due to the small sampling of subjects, no statistical analysis will be performed. Descriptive statistics in the form of counts calculated as percentages will be reported.
Measured: 19 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2014 (estimated)
- Study startJun 2015
- Primary completion18 Nov 2021
- Study completion27 Mar 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Southern Illinois University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Krishna Rao, MD, Principal investigator, Southern Illinois University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02324582
- Sponsor's protocol ID
- AL-SIUSOM-14-006
- Acronym
- MARC
- Status last verified
- Apr 2024
- First submitted
- 11 Dec 2014
- Last updated
- 3 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Jamil ML, Deebajah M, Sood A, Robinson K, Rao K, Sana S, Alanee S. Protocol for phase I study of pembrolizumab in combination with Bacillus Calmette-Guerin for patients with high-risk non-muscle invasive bladder cancer. BMJ Open. 2019 Jul 17;9(7):e028287. doi: 10.1136/bmjopen-2018-028287.
PubMed 31320352
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of MK-3475 in Combination With BCG for Patients With High Risk Superficial Bladder Cancer
- ClinicalTrials.gov ID
- NCT02324582
- Acronym / sponsor ID
- MARC / AL-SIUSOM-14-006
- Conditions
- Bladder Cancer
- Keywords
- Urinary Bladder Neoplasms, Mycobacterium bovis, Programmed Cell Death 1 Receptor, pembrolizumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Southern Illinois UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jun 2015 (actual)
- Primary completion
- 18 Nov 2021 (actual)
- Study completion
- 27 Mar 2023 (actual)
- First posted
- 24 Dec 2014 (estimated)
- Results
- Posted 3 Sep 2024
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 single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment for patients, 18 years or older, with high risk superficial bladder cancer (cancer not yet involving the muscle of the bladder wall) who have had removal of their bladder tumor. Patients will be enrolled to a single treatment group of a fixed dose of MK 3475 and BCG.
Detailed description
Bladder cancer is the fifth most common cancer in the United States. This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment. The study will determine the safety of administering MK-3475 at a fixed dose every three weeks in conjunction with intravesicular BCG treatment in non-muscle invasive bladder cancer patients who had recurrence after two courses of induction (6 doses) intravesical therapy (two BCG courses, or one BCG course and one other approved intravesical therapies) administered within 12 months, or after one induction (6 doses) and one maintenance (3 doses) intravesical therapy (BCG). Subjects will have confirmation of bladder cancer non-invasive to the muscle. Approximately 20 subjects will be screened to treat 15 eligible subjects with high risk superficial bladder cancer who have had transurethral resection of their bladder tumor.
The rationale for the use of the indicated dose of TICE® BCG is based upon FDA approved and commercially provided package insert/ instructions for use of the product. BCG installation has been used to treat non-muscle-invasive bladder cancer for more than 30 years. It is one of the most successful biotherapies for cancer in use. Despite long clinical experience with BCG, the mechanism of its therapeutic effect is still under investigation.
The first 3 subjects will be treated at a dose of 100 mg MK-3475 to ensure safety for the combination. If no safety or efficacy issues are present, dosing will be escalated to 200 mg MK-3475 every 3 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravenous MK-3475/ Intravesical BCG | Experimental | Drug: Intravenous MK-3475/ Intravesical BCG3 subjects will be treated at a dose of 100 mg MK-3475 at 100 mg every 3 weeks (Q3W) intravenously (IV) for 6 doses and 1 vial intravesicular BCG suspended in 50 ml preservative-free saline once per week of 6 weekly doses 12 subjects will be treated at a dose of 200 mg MK-3475 at 100 mg every 3 weeks (Q3W) intravenously (IV) for 6 doses and 1 vial intravesicular BCG suspended in 50 ml preservative-free saline once per week of 6 weekly doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 1.Willing and able to provide written informed consent/assent.
- 2.18 years of age.
- 3.Have pathologically documented high grade transitional cell superficial bladder cancer (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the bladder at time of initial resection for recurrent/persistent high risk transitional cell superficial bladder cancer.
- 4.Recurrent/persistent disease despite 2 Induction Intravesical Therapy Courses given within 12 months (with BCG being one of them), or despite one induction BCG treatment in addition to at least one maintenance course of BCG 5.Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
- 6.ECOG performance status of 0-2. 7.Demonstrate adequate organ function 8.Female subject of childbearing potential should have a negative urine or serum pregnancy.
Key exclusion criteria (21 listed)
- Currently has active or progressive metastatic disease.
- Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of 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 trial treatment.
- Prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for bladder cancer.
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 |
|---|---|---|
| Intravenous MK-3475/ Intravesical BCGAlso: pembrolizumab6 cycles (each cycle is 21 days) of pembrolizumab will be given over 9 weeks in combination with BCG. BCG treatment will begin on Day 1 of cycle 3 of pembrolizumab. | Drug | Intravenous MK-3475/ Intravesical BCG |
Primary outcome
Number of Participants With Grade 3, 4, and 5 Treatment Related Adverse Events
Time frame: change from baseline to 23 weeks
Grade and quantity of treatment related adverse events. Due to the small sampling of subjects, no statistical analysis will be performed. Descriptive statistics in the form of counts calculated as percentages will be reported.
1 secondary outcome
Number of Participants Without Bladder Tumors Upon Cystoscopy Following Treatment.
Time frame: 19 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31320352Jamil ML, Deebajah M, Sood A, Robinson K, Rao K, Sana S, Alanee S. Protocol for phase I study of pembrolizumab in combination with Bacillus Calmette-Guerin for patients with high-risk non-muscle invasive bladder cancer. BMJ Open. 2019 Jul 17;9(7):e028287. doi: 10.1136/bmjopen-2018-028287.
- Simmons Cancer Institute at Southern Illinois University School of MedicineLink 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.
Krishna Rao, MD principal investigator
Southern Illinois University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intravenous MK-3475/ Intravesical BCG in people with Bladder Cancer, run by Southern Illinois University at 3 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 6 inclusion and 21 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 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 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.
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 3 Sep 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?
Number of Participants With Grade 3, 4, and 5 Treatment Related Adverse Events (time frame: change from baseline to 23 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02324582, which also lists 1 linked publication.
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 3 Sep 2024.