Testing the PD-1 Inhibitor Pembrolizumab as Maintenance Therapy After Initial Chemotherapy in Metastatic Bladder Cancer

NCT02500121 | Completed Phase 2 Results DMC

• 1 other identifier: HCRN GU14-182
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 28

Brief Summary

This is a multi-institutional, randomized, placebo controlled, double-blinded phase II trial of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients with metastatic urothelial cancer who have achieved at least stable disease on first-line chemotherapy.

Conditions

Urothelial Carcinoma; Bladder Cancer

Keywords

Pembrolizumab; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Measured at the time from randomization to death or progression, depending on which occurs first, as per immune-related RECIST (irRECIST). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  Calculated after a median follow-up time of 12.9 months

Secondary Outcomes (5)

• 6-month PFS as Per irRECIST

  Six months after randomization

• Number of Subjects With Adverse Events as a Measure of the Safety and Tolerability of Pembrolizumab

  Every 3 weeks beginning with C1D1 for up to 24 months

• Objective Response Rate (ORR) Assessment of Subjects on Maintenance Pembrolizumab vs Placebo

  Response assessed every 12 weeks from the date of randomization to the date of documented disease progression or date of death, whichever occurs first, assessed for up to a maximum of 104 weeks (24 months)

• ORR Assessment of Subjects Receiving Pembrolizumab After Progressing on Placebo

  Every 12 weeks from the first treatment on the crossover to the date of documented disease progression, per irRECIST 1.1, assessed for up to a maximum of 104 weeks (24 months)

• Median Overall Survival (OS) Time in Subjects Treated With Pembrolizumab vs Placebo

  From randomization until death from any cause. Reported after a median follow-up of 12.9 months.

Study Arms (2)

Control Arm A

PLACEBO COMPARATOR

Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months.

Other: Placebo

Experimental Arm B

EXPERIMENTAL

Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months.

Drug: Pembrolizumab

Interventions

Placebo OTHER

Normal saline

Control Arm A

Pembrolizumab DRUG

Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months

Experimental Arm B

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status (PS) of ≤ 1 within fourteen days of registration for protocol therapy.
• Histological or cytological evidence of urothelial cancer of the bladder, urethra, ureter, or renal pelvis. Differentiation with variant histologies (e.g., squamous cell differentiated) will be permitted provided that the predominant histology is urothelial carcinoma.
• Metastatic and/or unresectable (cT4b) disease
• Must have achieved an objective response (CR/PR) or stable disease (SD) after 4 to 6 cycles of standard first-line platinum-based chemotherapy for mUC (e.g., as per NCCN guidelines). Able to commence study treatment within 2 to 6 weeks of receiving last dose of first-line chemotherapy.
• All subjects must have adequate archival tissue available prior to registration (i.e., at least 20 unstained slides or paraffin block). If acceptable archival tissue is not available, the subject must be willing to consent to providing a core or excisional biopsy for research prior to registration for protocol therapy. If archival tissue is not available and there are no sites amenable to biopsy, enrollment must be discussed with the sponsor-investigator on a case by case basis.
• Female subjects of childbearing potential must have a negative serum pregnancy within three days prior to registration for protocol therapy
• Sexually active, pre-menopausal women of childbearing potential must be willing to use an adequate method of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study drug. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> one year.
• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug.

You may not qualify if:

• More than one line of prior chemotherapy for metastatic or locally advanced disease, with the following exception:
• Prior neoadjuvant/adjuvant chemotherapy will not count as line of therapy if completed greater than 12 months prior to initiation of chemotherapy regimen for metastatic or unresectable disease.
• Current or past participation in a study of an investigational agent or using an investigational device within four weeks of registration for protocol therapy.
• A diagnosis of immunodeficiency or is receiving treatment with systemic steroid therapy or any other form of immunosuppressive therapy within seven days prior to registration for protocol therapy.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within two weeks prior to registration for protocol therapy. Note: If the subjects have undergone major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting protocol therapy.
• 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, or in situ cervical cancer that has undergone potentially curative therapy.
• A known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to registration for protocol therapy and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least seven days prior to registration for protocol therapy.
• Active autoimmune disease that has required systemic treatment in 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 evidence of active, non-infectious pneumonitis.
• Has a history of interstitial lung disease.
• An active infection requiring systemic therapy.
• 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.
• 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 screening period through 120 days after the last dose of protocol therapy.
• 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). Examples include nivolumab, MPDL3280, etc.

Sponsors & Collaborators

• Matthew Galsky: lead
• Hoosier Cancer Research Network: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (28)

University of Arizona at Dignity Health St. Joseph's

Phoenix, Arizona, 85004, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

IU Health Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Central Indiana Cancer Center

Indianapolis, Indiana, 46219, United States

Location

Community Regional Cancer Care

Indianapolis, Indiana, 46256, United States

Location

Community Healthcare System

Munster, Indiana, 46321, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University: Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

GU Cancer Research Network, LLC

Omaha, Nebraska, 68130, United States

Location

The John Theuer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Related Publications (1)

• Galsky MD, Mortazavi A, Milowsky MI, George S, Gupta S, Fleming MT, Dang LH, Geynisman DM, Walling R, Alter RS, Kassar M, Wang J, Gupta S, Davis N, Picus J, Philips G, Quinn DI, Haines GK 3rd, Hahn NM, Zhao Q, Yu M, Pal SK. Randomized Double-Blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer. J Clin Oncol. 2020 Jun 1;38(16):1797-1806. doi: 10.1200/JCO.19.03091. Epub 2020 Apr 9.

  PMID: 32271672 DERIVED

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Clinical Trials Results Coordinator
• Organization: Hoosier Cancer Research Network

aneal@hoosiercancer.org

317-634-5842

Study Officials

• Matthew Galsky, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 16, 2015
• Study Start: November 11, 2015
• Primary Completion: July 1, 2019
• Study Completion: January 1, 2021
• Last Updated: September 30, 2022
• Results First Posted: September 30, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (28)