High Risk Superficial Upper Urinary Tract Transitional Cell CarcinomaPhase 2NCT03345134
Pembrolizumab in Combination With BCG After Ablation in Patients With UUTTCC Without Nephroureterectomy
A Phase 2 study testing MK-3475 and BCG in people with High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma and Endoscopic Surgical Procedure, run by Shaheen Alanee at 1 site in United States.
Trial summary
PURPOSE: This study is being conducted to test the safety of the study drug Pembrolizumab, also known as MK-3475, at different dose levels in combination with the current therapy, (BCG), for superficial upper urinary tract transitional cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma, Endoscopic Surgical Procedure, Transitional Epithelial Cells
- What is being tested?
- MK-3475 and BCG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2017to 1 Jan 2021
- 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
- Be willing and able to provide written informed consent for the trial.
- Be at least18 years of age on day of signing informed consent.
- Have pathologically documented high grade UUTTCC (CIS, Ta, T1) that could be completely ablated with ureteroscopy or through antegrade percutaneous access.
- Subject must also unwilling or unfit to undergo treatment with radical nephroureterectomy
- Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Tissue must be obtained from the most recent upper urinary tract biopsy.
- Have a performance status of 0-1 on the ECOG Performance Scale (Appendix A).
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- Demonstrate adequate organ function, all screening labs should be performed within 28 days of treatment initiation.
- Female subject of childbearing potential should have a negative urine or serum pregnancy test 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 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 (Reference Section 5.5.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- 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.
- Patients who received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for UUTTCC are allowed into the study as long as there is confirmed recurrence of the disease after previous treatment and the patient is unwilling or unfit to undergo radical surgery.
Who cannot join
- Currently has active or progressive metastatic disease. (Chest X-ray, Computerized Tomography [CT] urogram or Magnetic Resonance Imaging [MRI], and urogram are allowed to ascertain the superficial nature of the disease when indicated, but not required. If urogram protocol is not available or contrast allergy/poor renal function precludes such imaging, then non-contrast CT or MRI of the abdomen/pelvis within 90 days of study entry will suffice.)
- 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.
- Has had a prior monoclonal antibody within 4 weeks before 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.
- Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for UUTTCC.
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer with no recurrence after curative surgery or radiation, or in situ cervical cancer that has undergone potentially curative therapy. Lower urinary tract transitional cell carcinoma is also allowable on study as high risk transitional cell carcinoma is commonly multifocal, and intraluminal BCG therapy is also used for treatment of lower urinary tract lesions in a manner similar to that of UUTTCC.
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- 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.
- Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease, or active , non-infectious pneumonitis.
- Has an active infection, including a concurrent febrile illness, 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 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 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 renal pelvis 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 renal pelvis.
- Less than 14 days post renal pelvis biopsy, TUR, or traumatic catheterization.
- Evidence of muscle invasive renal pelvis cancer, or transitional cell carcinoma of the upper urinary tract
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Shaheen Alanee, MD, MPH, MBA
Detroit, Michigan, 48202
Shaheen Alanee, MD, MPH, MBA, 313-399-8275, salanee1@hfhs.org
About this study
Official title: Phase II Study of Pembrolizumab in Combination With BCG After Endoscopic Ablation for Patients With High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma Unfit or Unwilling to be Treated With Nephroureterectomy
PURPOSE: This study is being conducted to test the safety of the study drug Pembrolizumab, also known as MK-3475, at different dose levels in combination with the current therapy, (BCG), for superficial upper urinary tract transitional cell carcinoma. We want to find out what effects, good and/or bad, it has on upper urinary transitional cell carcinoma OBJECTIVE: To determine the safety of administering MK-3475 at a fixed dose of 200 mg every three weeks in conjunction with intrapelvic BCG treatment in high risk superficial UUTTCC patients who are unfit or unwilling to be treated with radical nephroureterectomy.
STUDY DESIGN: Open-label, single center, Phase II, treatment trial TREATMENT: BCG- BCG treatment could be delivered both through a retrograde ureteral catheter placed under fluoroscopic control or through an antegrade nephrostomy tube placed by interventional radiology. Treatment will be once a week for 6 weeks. BCG treatment will begin on Day 1 of Week 7. Depending on patient's response, they may have additional treatments beyond the 6 scheduled, but they will be outside of the patient's participation in this study. Pembrolizumab will be given through an intravenous needle once every 21 days (one cycle) for a total of 6 cycles. It will take 30 minutes for the infusion of the study drug. Pembrolizumab will be given on Day 1 of weeks 1, 4, 7, 10, 13, and 16 while BCG will be given on Day 1 of weeks 7-12.
PROCEDURES: Following informed consent, prescreening and screening procedures will be performed, which will include medical history review, baseline chest x ray and EKG, ureteroscopy and pulmonary function tests for final eligibility status. Once subject is eligible, they will undergo physical exams (every 3 weeks), vital signs and weight (each study visit), adverse event monitoring (each study visit), ECGs (screening visit), bloodwork (at screening and then every 3 weeks), urinalysis at selected study visits, and concomitant medication review (each study visit), and questionnaires (selected study visits). After subject has completed week 19, they will have a study discontinuation visit, followed by a 30 day follow up visit. The subject will then be followed at 3, 6, 9, 12, 18 and 24 months post treatment where vital status will be determined as well as disease recurrence status. Ureteroscopy will be performed as standard of care but will be considered measures for efficacy. Biopsy will be performed as clinically indicated.
- Conditions
- High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma, Endoscopic Surgical Procedure, Transitional Epithelial Cells
- Being tested
- MK-3475 and BCG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3475 and BCGDrug
combination treatment with MK-3475 and BCG after endoscopic ablation
| Study group | Role | What they receive |
|---|---|---|
| MK-3475 and BCG | Experimental | Single treatment group of high risk superficial upper urinary tract transitional cell carcinoma; combination treatment with MK-3475 and BCG Receives: Drug: MK-3475 and BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response per ureteroscopy and pathological confirmation of tissue biopsy
Measured: At 19 weeks
Secondary outcomes (1)
Complete Response per ureteroscopy and pathological confirmation of tissue biopsy
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start30 Nov 2017 (estimated)
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Jan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for High Risk Superficial Upper Urinary Tract Transitional Cell CarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shaheen Alanee
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Shaheen Alanee, Henry Ford Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03345134
- Sponsor's protocol ID
- HFHS 16-01
- Status last verified
- Nov 2017
- First submitted
- 3 Nov 2017
- Last updated
- 17 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Jamil ML, Deebajah M, Sood A, Alanee S. Combination of pembrolizumab and BCG treatment after endoscopic ablation of high-risk superficial upper urinary tract urothelial carcinoma in patients not candidates for radical nephroureterectomy: protocol for phase-II study. BMJ Open. 2019 Dec 3;9(12):e027066. doi: 10.1136/bmjopen-2018-027066.
PubMed 31796469
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Pembrolizumab in Combination With BCG After Endoscopic Ablation for Patients With High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma Unfit or Unwilling to be Treated With Nephroureterectomy
- ClinicalTrials.gov ID
- NCT03345134
- Acronym / sponsor ID
- HFHS 16-01
- Conditions
- High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma, Endoscopic Surgical Procedure, Transitional Epithelial Cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Shaheen AlaneeUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 30 Nov 2017 (estimated)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Jan 2021 (estimated)
- First posted
- 17 Nov 2017 (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.
PURPOSE: This study is being conducted to test the safety of the study drug Pembrolizumab, also known as MK-3475, at different dose levels in combination with the current therapy, (BCG), for superficial upper urinary tract transitional cell carcinoma. We want to find out what effects, good and/or bad, it has on upper urinary transitional cell carcinoma OBJECTIVE: To determine the safety of administering MK-3475 at a fixed dose of 200 mg every three weeks in conjunction with intrapelvic BCG treatment in high risk superficial UUTTCC patients who are unfit or unwilling to be treated with radical nephroureterectomy.
STUDY DESIGN: Open-label, single center, Phase II, treatment trial TREATMENT: BCG- BCG treatment could be delivered both through a retrograde ureteral catheter placed under fluoroscopic control or through an antegrade nephrostomy tube placed by interventional radiology. Treatment will be once a week for 6 weeks. BCG treatment will begin on Day 1 of Week 7. Depending on patient's response, they may have additional treatments beyond the 6 scheduled, but they will be outside of the patient's participation in this study. Pembrolizumab will be given through an intravenous needle once every 21 days (one cycle) for a total of 6 cycles. It will take 30 minutes for the infusion of the study drug. Pembrolizumab will be given on Day 1 of weeks 1, 4, 7, 10, 13, and 16 while BCG will be given on Day 1 of weeks 7-12.
PROCEDURES: Following informed consent, prescreening and screening procedures will be performed, which will include medical history review, baseline chest x ray and EKG, ureteroscopy and pulmonary function tests for final eligibility status. Once subject is eligible, they will undergo physical exams (every 3 weeks), vital signs and weight (each study visit), adverse event monitoring (each study visit), ECGs (screening visit), bloodwork (at screening and then every 3 weeks), urinalysis at selected study visits, and concomitant medication review (each study visit), and questionnaires (selected study visits). After subject has completed week 19, they will have a study discontinuation visit, followed by a 30 day follow up visit. The subject will then be followed at 3, 6, 9, 12, 18 and 24 months post treatment where vital status will be determined as well as disease recurrence status. Ureteroscopy will be performed as standard of care but will be considered measures for efficacy. Biopsy will be performed as clinically indicated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MK-3475 and BCG | Experimental | Drug: MK-3475 and BCGSingle treatment group of high risk superficial upper urinary tract transitional cell carcinoma; combination treatment with MK-3475 and BCG |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Be willing and able to provide written informed consent for the trial.
- Be at least18 years of age on day of signing informed consent.
- Have pathologically documented high grade UUTTCC (CIS, Ta, T1) that could be completely ablated with ureteroscopy or through antegrade percutaneous access.
- Subject must also unwilling or unfit to undergo treatment with radical nephroureterectomy
- Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Tissue must be obtained from the most recent upper urinary tract biopsy.
Key exclusion criteria (20 listed)
- Currently has active or progressive metastatic disease. (Chest X-ray, Computerized Tomography [CT] urogram or Magnetic Resonance Imaging [MRI], and urogram are allowed to ascertain the superficial nature of the disease when indicated, but not required. If urogram protocol is not available or contrast allergy/poor renal function precludes such imaging, then non-contrast CT or MRI of the abdomen/pelvis within 90 days of study entry will suffice.)
- 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.
- Has had a prior monoclonal antibody within 4 weeks before 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.
- Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for UUTTCC.
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
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 |
|---|---|---|
| MK-3475 and BCGcombination treatment with MK-3475 and BCG after endoscopic ablation | Drug | MK-3475 and BCG |
Primary outcome
Complete Response per ureteroscopy and pathological confirmation of tissue biopsy
Time frame: At 19 weeks
1 secondary outcome
Complete Response per ureteroscopy and pathological confirmation of tissue biopsy
Time frame: Up to 24 months
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 17 Nov 2017.
- Derived from this study: PubMed 31796469Jamil ML, Deebajah M, Sood A, Alanee S. Combination of pembrolizumab and BCG treatment after endoscopic ablation of high-risk superficial upper urinary tract urothelial carcinoma in patients not candidates for radical nephroureterectomy: protocol for phase-II study. BMJ Open. 2019 Dec 3;9(12):e027066. doi: 10.1136/bmjopen-2018-027066.
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.
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 MK-3475 and BCG in people with High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma and Endoscopic Surgical Procedure, run by Shaheen Alanee 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 11 inclusion and 20 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: opening soon, as of the sponsor's last update on 17 Nov 2017. 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?
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 Shaheen Alanee, MD, MPH, MBA (313-399-8275, Salanee1@hfhs.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response per ureteroscopy and pathological confirmation of tissue biopsy (time frame: At 19 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 NCT03345134, 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 17 Nov 2017.