Pembrolizumab-Epacadostat Combination to Treat Muscle-invasive Bladder UrotheLIAl canceR: PECULIAR Study (PECULIAR)

February 24, 2021 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

PECULIAR: An Open Label, Monocenter, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab and Epacadostat, Preceding Radical Cystectomy, for Patients With Muscle-invasive Bladder Cancer.

An open label, monocenter, single-arm, phase 2 study of neoadjuvant pembrolizumab and epacadostat, preceding radical cystectomy, for patients with muscle-invasive bladder cancer.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

An open label, monocenter, single-arm, phase 2 study

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale Tumori

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
  2. Male/female participants who are at least 18 years of age will be enrolled in this study.
  3. A male participant must agree to use a contraception during the treatment period and for at least [120 days, corresponding to time needed to eliminate any study treatments) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment and refrain from donating sperm during this period.
  4. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) or b.) A WOCBP who agrees to follow the contraceptive during the treatment period and for at least [120 days (corresponding to time needed to eliminate any study treatments) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity] after the last dose of study treatment.
  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  6. Have adequate organ function as defined in the following table Specimens must be collected within 10 days prior to the start of study treatment.
  7. Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
  8. Fit and planned for cystectomy (according to local guidelines).
  9. Clinical stage T2-T3a confirmed by TURB
  10. N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of initial study treatment by RECIST v1.1).

Exclusion Criteria:

  1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137, IDO1).
  3. Has received prior systemic anti-cancer therapy including investigational agents.
  4. Has received prior radiotherapy on the bladder tumor.
  5. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

  6. Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.

    Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

  7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

  8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

    Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early stage prostate cancer defined as follows are not excluded; Stage T1c or T2a with a Gleason score ≤ 6 and prostatic-specific antigen (PSA) < 10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation.

  9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  10. Has 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.
  11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  12. Has an active infection requiring systemic therapy.
  13. Has a known history of Human Immunodeficiency Virus (HIV).
  14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
  15. Has a known history of active TB (Bacillus Tuberculosis).
  16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  18. Pregnant or breastfeeding.
  19. Inability to swallow tablets or capsules

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab + Epacadostat
Pembrolizumab 200 mg IV every 3 weeks (for 3 cycles) Epacadostat 300 mg (BID) orally continuously every 28 days (for 3 cycles)
Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks (for 3 cycles)
Other Names:
  • KEYTRUDA
Drug: Epacadostat
Epacadostat 300 mg (BID) orally continuously every 28 days (for 3 cycles)
Other Names:
  • previously INCB24360

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic complete response (pCR)
Time Frame: 12 months
To assess whether pembrolizumab and epacadostat combination results in pathological complete response rates (herein referred to as either "pT0" or "pCR")
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Responses to treatment
Time Frame: 12 months
To evaluate radiological response on those patients with measurable disease (at baseline). Response (CR and PR) after 3 cycles of treatment with the study drug.
12 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability).
Time Frame: 12 months
incidence, nature and severity of all-cause and treatment-related adverse events (AE), graded with the Common Terminology Criteria for Adverse Events (CTCAE).
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PD-L1 expression and IDO1 expression
Time Frame: 12 months
identify potential biomarkers that could be used for correlation with response and outcome in this setting of bladder cancer patients as well as more advanced settings in this indication.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Andrea Necchi, MD, Fondazione IRCCS Istituto Nazionale Tumori-Milano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 22, 2019

Primary Completion (Actual)

May 22, 2019

Study Completion (Actual)

May 22, 2019

Study Registration Dates

First Submitted

January 31, 2019

First Submitted That Met QC Criteria

February 4, 2019

First Posted (Actual)

February 6, 2019

Study Record Updates

Last Update Posted (Actual)

February 26, 2021

Last Update Submitted That Met QC Criteria

February 24, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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