Pembrolizumab and BCG Solution in Treating Patients With Recurrent Non-Muscle-Invasive Bladder Cancer

NCT02808143 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: NU 15U06STU00202754P30CA060553NCI-2016-00664
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy (the effect of drug on tumor) and the tolerability (the effect of drug on the body) of pembrolizumab, when given as a single agent in patients with bladder tumors. Another purpose of the study is to see what tumor characteristics are associated with increased efficacy of the pembrolizumab. Pembrolizumab (MK-3475) is an antibody (a human protein that sticks to a part of the tumor and/or immune cells) designed to allow the body's immune system to work against tumor cells. Pembrolizumab is Food and drug Administration (FDA) approved for the treatment of advanced melanoma (a type of skin cancer) and some types of lung cancer. It is not yet approved by the United States Food and Drug Administration (USFDA) for bladder cancer, hence it is considered an investigational agent for this disease.

Conditions

Recurrent Bladder Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Determine the MTD of the study drug (MK-3475) when administered intravesically in combination with BCG in patients with high risk or BCG-refractory non-muscle-invasive bladder cancer (up to the individual maximum tolerated dose of each drug alone). The MTD will be defined as the highest dose that causes dose limiting toxicities (DLTs) in \<2 of 6 patients graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  Up to 9 weeks

Secondary Outcomes (2)

• Dose Limiting Toxicities (DLTs)

  Up to 9 weeks

• Incidence of Adverse Events

  Up to 30 days from the last dose of study drug, up to 2.5 years

Other Outcomes (12)

• Change in Cytokines in the Blood

  At weeks -2, 0, and 17

• Change in Cytokines in Urine

  Up to week 49

• Expression of PD-L1

  At baseline and then up to 49 weeks

Study Arms (1)

Treatment (pembrolizumab, BCG solution)

EXPERIMENTAL

PRE-INDUCTION PHASE: Patients receive pembrolizumab intravesically once on day -14. INDUCTION PHASE: Patients receive BCG solution intravesically once weekly for 6 weeks at weeks 0-5 and pembrolizumab intravesically every 2 weeks at weeks 0, 2, and 4. MAINTENANCE PHASE: Beginning 2 weeks after the last dose of BCG solution, patients receive pembrolizumab intravesically every 2 weeks for 12 weeks at weeks 7, 9, 11, 13, 15, and 17 for a total of 6 doses. Patients then receive pembrolizumab intravesically every 4 weeks at weeks 21, 25, 29, 33, 37, 41, 45, and 49 for a total of 8 doses.

Biological: BCG Solution; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Pharmacological Study

Interventions

BCG Solution BIOLOGICAL

Given intravesically

Also known as: Bacillus Calmette-Guerin Solution, TICE BCG Solution

Treatment (pembrolizumab, BCG solution)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, BCG solution)

Pembrolizumab BIOLOGICAL

Given intravesically

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, BCG solution)

Pharmacological Study OTHER

Correlative studies

Treatment (pembrolizumab, BCG solution)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically documented recurrence of non-muscle-invasive bladder carcinoma (T1HG, T1HG after repeat transurethral resection \[reTUR\]) or BCG refractory; if patient has received BCG they can be Ta, Tis, or T1)
• Patients must have persistent high grade disease OR be BCG refractory, defined as either:
• Recurrence within 6 months of receiving at least 2 courses of intravesical BCG (at least 5 or 6 inductions and at least 2 or 3 maintenance doses) or
• T1 high grade disease at the first evaluation following induction BCG alone (at least 5 of 6 induction doses)
• Patients must agree to provide tissue from archival biopsy samples or newly obtained excisional biopsy of a tumor lesion
• NOTE: Patients who do not have available specimens from previous biopsy or do not agree to provide this tissue are not eligible; cytological specimens will not be acceptable; availability of tissue must be confirmed at the time of registration, but the actual sample does not have to be received in order to complete registration
• Patients must have received one course of induction treatment with BCG (4-6 weekly doses), irrespective of the interval since last treatment; patients are allowed to have received any number of prior chemotherapy instillations
• NOTE: Patients may have received prior intravesical interferon
• All patients must have imaging (computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\]) documenting normal upper urinary tracts and absence of locally advanced bladder cancer within 60 days prior to study registration
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Absolute neutrophil count (ANC) \>= 1,500 /mcL within 14 days prior to registration
• Platelets \>= 100,000 / mcL within 14 days prior to registration
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L within 14 days prior to registration
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated (creatinine clearance should be calculated per institutional standard) creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN within 14 days prior to registration
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN within 14 days prior to registration

You may not qualify if:

• Patients who have had chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day -14 or who have not recovered (to =\< grade 1 or baseline) from adverse events due to a previously administered agent are not eligible
• Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and do qualify for the study
• Note: if subject received major surgery within 4 weeks prior to day -14, they must have recovered adequately from the toxicity and/or complications per PI discretion
• Patients may not be receiving any other investigational agents within 4 weeks of the first dose of treatment
• Patients who have received a prior monoclonal antibody within 4 weeks prior to study day -14 or who have not recovered (to =\< grade 1 or baseline) from adverse events due to agents administered more than 4 weeks earlier are not eligible
• Patients who have a diagnosis of immunodeficiency (per PI discretion) or who have received treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to study registration are not eligible
• NOTE: patients who have received acute, low-dose, systemic immunosuppressant medications (eg, one-time dose of dexamethasone for nausea) may be enrolled in the study; the use of inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone) is allowed
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 are not eligible AND/OR patients who have had prior exposure to compounds of similar chemical or biologic composition to MK-3475 are not eligible
• Patients who have documentation of an uncontrolled intercurrent illness (as noted in their medical records) including, but not limited to any of the following, are not eligible
• Ongoing or active infection requiring systemic treatment
• Symptomatic congestive heart failure (New York Heart Association cardiac disease class III or IV)
• Unstable angina pectoris
• Myocardial infarction within the previous 3 months
• Unstable cardiac arrhythmias
• Psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Northwestern University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Meghani K, Cooley LF, Choy B, Kocherginsky M, Swaminathan S, Munir SS, Svatek RS, Kuzel T, Meeks JJ. First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guerin. Eur Urol. 2022 Dec;82(6):602-610. doi: 10.1016/j.eururo.2022.08.004. Epub 2022 Aug 23.

  PMID: 36008193 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Joshua Meeks, MD, PhD
• Organization: Northwestern University Feinberg School of Medicine

Joshua.meeks@northwestern.edu

312-363-8959

Study Officials

• Joshua Meeks

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Joshua Meeks, MD, PhD

Study Record Dates

• First Submitted: May 25, 2016
• First Posted: June 21, 2016
• Study Start: February 10, 2017
• Primary Completion: May 15, 2020
• Study Completion: August 5, 2022
• Last Updated: June 26, 2024
• Results First Posted: October 20, 2022

Record last verified: 2024-06

Locations

US (1)