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

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ClinicalTrials.gov Identifier: NCT03832673
Recruitment Status : Not yet recruiting
First Posted : February 6, 2019
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

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

Condition or disease Intervention/treatment Phase
Muscle-invasive Bladder Cancer Drug: Pembrolizumab Drug: Epacadostat Phase 2

Detailed Description:
An open label, monocenter, single-arm, phase 2 study

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

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 Name: KEYTRUDA

Drug: Epacadostat
Epacadostat 300 mg (BID) orally continuously every 28 days (for 3 cycles)
Other Name: previously INCB24360




Primary Outcome Measures :
  1. 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")


Secondary Outcome Measures :
  1. 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.

  2. 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).


Other Outcome Measures:
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03832673


Contacts
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Contact: Andrea Necchi, MD +390223902402 andrea.necchi@istitutotumori.mi.it
Contact: Rosanna Montone, Dr.ssa +390223903817 rosanna.montone@istitutotumori.mi.it

Locations
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Italy
Fondazione IRCCS Istituto Nazionale Tumori Not yet recruiting
Milan, Italy, 20133
Contact: Andrea Necchi, MD    +390223902402    andrea.necchi@istitutotumori.mi.it   
Contact: Rosanna Montone, Dr.ssa    +390223903817    rosanna.montone@istitutotumori.mi.it   
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
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Principal Investigator: Andrea Necchi, MD Fondazione IRCCS Istituto Nazionale Tumori-Milano

Publications:

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Responsible Party: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT03832673     History of Changes
Other Study ID Numbers: NT
First Posted: February 6, 2019    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:
bladder
cancer

Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents