MK-3475/BCG in High Risk Superficial Bladder Cancer

NCT02324582 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AL-SIUSOM-14-006
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief 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. Patients will be enrolled to a single treatment group of a fixed dose of MK 3475 and BCG.

Conditions

Bladder Cancer

Keywords

Urinary Bladder Neoplasms; Mycobacterium bovis; Programmed Cell Death 1 Receptor; pembrolizumab

Outcome Measures

Primary Outcomes (1)

• 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.

  change from baseline to 23 weeks

Secondary Outcomes (1)

• Number of Participants Without Bladder Tumors Upon Cystoscopy Following Treatment.

  19 weeks

Study Arms (1)

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

Drug: Intravenous MK-3475/ Intravesical BCG

Interventions

Intravenous MK-3475/ Intravesical BCG DRUG

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.

Also known as: pembrolizumab

Intravenous MK-3475/ Intravesical BCG

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent/assent.
• years of age.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Southern Illinois University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Simmons Cancer Institute-SIU School of Medicine

Springfield, Illinois, 62702, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Henry Ford Health Systems

Detroit, Michigan, 48202, United States

Location

Related Publications (1)

• 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.

  PMID: 31320352 DERIVED

Related Links

• Simmons Cancer Institute at Southern Illinois University School of Medicine

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

Limitations and Caveats

The study is limited by the small number of subjects treated and evaluated which did allow for statistical analysis.

Results Point of Contact

• Title: Dr. Krishna Rao
• Organization: Southern Illinois University School of Medicine

krao@siumed.edu

217-545-7969

Study Officials

• Krishna Rao, MD

  Southern Illinois University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2014
• First Posted: December 24, 2014
• Study Start: June 1, 2015
• Primary Completion: November 18, 2021
• Study Completion: March 27, 2023
• Last Updated: September 3, 2024
• Results First Posted: September 3, 2024

Record last verified: 2024-04

Locations

US (3)