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Platform Study for Prostate Researching Translational Endpoints Correlated to Response to Inform Use of Novel Combinations (PORTER)

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ClinicalTrials.gov Identifier: NCT03835533
Recruitment Status : Recruiting
First Posted : February 8, 2019
Last Update Posted : November 18, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
Celldex Therapeutics
Cancer Research Institute, New York City
Inovio Pharmaceuticals
Oncovir, Inc.
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy

Brief Summary:
This study is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of immunotherapy combinations in participants with mCRPC who have received prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Drug: NKTR-214 (Cohort A) Drug: Nivolumab (Cohort A, B and C) Radiation: Stereotactic body radiation therapy (SBRT) (Cohort B) Drug: CDX-301 (Cohort B and C) Drug: Poly-ICLC (Cohort B) Drug: INO-5151 (Cohort C) Device: Cellectra 2000 Phase 1

Detailed Description:

This is an open-label, non-randomized, exploratory platform protocol designed to assess the safety and antitumor activity of multiple immunotherapy combinations in participants with mCRPC who have received prior therapy. The platform study will consist of 2 stages: Stage 1, an initial stage to evaluate safety, biomarkers, and clinical activity of a combination and Stage 2, an expanded cohort, when warranted, based on the safety, clinical activity, and/or biomarker results from Stage 1. The Sponsor intends to modify and/or add new combinations to the protocol as data emerge from this and other trials.

Participants must provide consent for archival tissue from a prior biopsy or surgery for prostate cancer and must consent to baseline and on-treatment biopsies, if medically feasible. Participants will be assigned to receive one of the enrolling combination study interventions and will be monitored for safety and response.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
Actual Study Start Date : June 21, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Cohort A: NKTR-214 + Nivolumab Drug: NKTR-214 (Cohort A)
NKTR-214 will be administered intravenously every 3 weeks for up to 2 years

Drug: Nivolumab (Cohort A, B and C)
Nivolumab will be administered intravenously every 3 weeks for up to 2 years to cohort A, every 4 weeks for up to 2 years for cohort B and C.
Other Name: Opdivo

Experimental: Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab Drug: Nivolumab (Cohort A, B and C)
Nivolumab will be administered intravenously every 3 weeks for up to 2 years to cohort A, every 4 weeks for up to 2 years for cohort B and C.
Other Name: Opdivo

Radiation: Stereotactic body radiation therapy (SBRT) (Cohort B)
Radiation therapy will be administered at 30 - 50 Gy in 1 - 5 doses, starting on Day 1 or 2 of Cycle 1

Drug: CDX-301 (Cohort B and C)
CDX-301 will be subcutaneously once a day for 5 days for cohort B. CDX-301 will be subcutaneously once a day for 10 days of immune-priming lead-in for cohort C.

Drug: Poly-ICLC (Cohort B)
Poly-ICLC will be administered intramuscularly twice weekly for 3 weeks starting on Day 1 of Cycle 1

Experimental: Cohort C: CDX-301 + INO-5151 + Nivolumab Drug: Nivolumab (Cohort A, B and C)
Nivolumab will be administered intravenously every 3 weeks for up to 2 years to cohort A, every 4 weeks for up to 2 years for cohort B and C.
Other Name: Opdivo

Drug: CDX-301 (Cohort B and C)
CDX-301 will be subcutaneously once a day for 5 days for cohort B. CDX-301 will be subcutaneously once a day for 10 days of immune-priming lead-in for cohort C.

Drug: INO-5151 (Cohort C)
INO-5151 will be administered intramuscularly on Day 8 of the Immune-priming Lead-in, and on day 1 of Cycle 1, 2 and 3, then every 12 weeks thereafter

Device: Cellectra 2000
Electroporation device




Primary Outcome Measures :
  1. Incidence and severity of adverse events [ Time Frame: Up to 2.5 years ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Up to 2.5 years ]
    ORR is a composite endpoint where response is defined as a participant meeting at least one of the following: circulating tumor cells change from unfavorable to favorable ; ≥ 50% reduction in Prostate-Specific Antigen (PSA) from baseline; confirmed complete response (CR) or partial response (PR)

  2. Disease control rate [ Time Frame: At 9 months ]
    Defined as CR, PR, or stable disease (SD) for 9 months as best response by Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  3. Radiographic progression-free survival (rPFS) [ Time Frame: Up to 2.5 years ]
    Defined as time from initiation of study intervention to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first)

  4. Overall survival (OS) [ Time Frame: Up to 2.5 years ]
    Defined as the time from initiation of study invention until death due to any cause

  5. Overall survival (OS) at 12 months [ Time Frame: At 12 months ]
    Defined as the time from initiation of study invention until death due to any cause



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Metastatic castration resistant prostate cancer with castrate-level testosterone (< 50 ng/dL) at screening.
  2. Disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
  3. Provide fresh pre-treatment core needle or incisional biopsy of a metastatic tumor lesion not previously irradiated. Fine needle aspiration is not acceptable.

    1. Additionally, if a pre-treatment biopsy is not medically feasible for participants with bone only disease, formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be provided.
    2. For all participants, in addition to fresh pre-treatment biopsy, consent for archival tissue is required.
  4. Must be willing to undergo tumor biopsy(ies) on treatment, if medically feasible.
  5. Have received and progressed on prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).
  6. Participants must discontinue antiandrogen therapy (ie, bicalutamide, flutamide, nilutamide) at least 4-6 weeks prior to registration with no evidence of PSA decline after washout.

    1. Bicalutamide: Washout period at least 6 weeks
    2. Flutamide and nilutamide: Washout period at least 4 weeks
  7. Participants must discontinue therapies for mCRPC for 5 half-lives or 28 days, whichever is shorter.

    1. Participants will remain on gonadotropin-releasing hormone (GnRH) agents throughout this study.
    2. Prior chemotherapy is allowed if no progression of disease on chemotherapy as defined by PCWG3-modified RECIST 1.1.
    3. Prior treatment with sipuleucel-T, radium-223, or poly ADP ribose polymerase (PARP) inhibitor (eg, olaparib) is allowed.
    4. Tissue biopsy may be performed during washout period.

Key Exclusion Criteria:

  1. Has a diagnosis of immunodeficiency or conditions that need systemic corticosteroid replacement therapy > 10 mg/day prednisone (or equivalent) or other immunosuppressive medications within 28 days prior to the first dose of study intervention. Inhaled steroids are permitted if necessary.
  2. Has any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring systemic treatment, or other conditions under control are permitted to enroll.
  3. Has a known history of active TB (Bacillus Tuberculosis).
  4. Has known history of, or any evidence of active, non-infectious pneumonitis.
  5. Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS), or any positive test for hepatitis B or hepatitis C virus representing acute or chronic disease.
  6. Has received a live vaccine within 30 days of planned start of study intervention.

    Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed.

  7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention 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 7 days prior to study intervention. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

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): NCT03835533


Contacts
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Contact: Recruiting sites have contact information. Please contact the site directly. If there is no contact info, please email porter0033@parkerici.org

Locations
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United States, California
Angeles Clinic Recruiting
Los Angeles, California, United States, 90025
Contact: Saba Mukarram    310-231-2181    smukarram@theangelesclinic.org   
Principal Investigator: Kristopher Wentzel, MD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Rebecca Holman, CCRP    415-476-2958    Rebecca.Holman@ucsf.edu   
Principal Investigator: Lawrence Fong, MD         
United States, New York
Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Matthew Galsky, MD    212-659-5452    matthew.galsky@mssm.edu   
Principal Investigator: Matthew Galsky, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Patient Referral Service    800-525-2225    referran@mskcc.org   
Principal Investigator: Karen Autio, MD MSc         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Julie Graff, MD    503-220-8262    graffj@ohsu.edu   
Sponsors and Collaborators
Parker Institute for Cancer Immunotherapy
Bristol-Myers Squibb
Celldex Therapeutics
Cancer Research Institute, New York City
Inovio Pharmaceuticals
Oncovir, Inc.
Investigators
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Study Director: Ramy Ibrahim, MD Parker Institute for Cancer Immunotherapy

Publications:
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjörd JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jäger N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, López-Otín C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdés-Mas R, van Buuren MM, van 't Veer L, Vincent-Salomon A, Waddell N, Yates LR; Australian Pancreatic Cancer Genome Initiative; ICGC Breast Cancer Consortium; ICGC MMML-Seq Consortium; ICGC PedBrain, Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR. Signatures of mutational processes in human cancer. Nature. 2013 Aug 22;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14. Erratum in: Nature. 2013 Oct 10;502(7470):258. Imielinsk, Marcin [corrected to Imielinski, Marcin].
Sydes MR, Spears MR, Mason MD, Clarke NW, Dearnaley DP, de Bono JS, Attard G, Chowdhury S, Cross W, Gillessen S, Malik ZI, Jones R, Parker CC, Ritchie AWS, Russell JM, Millman R, Matheson D, Amos C, Gilson C, Birtle A, Brock S, Capaldi L, Chakraborti P, Choudhury A, Evans L, Ford D, Gale J, Gibbs S, Gilbert DC, Hughes R, McLaren D, Lester JF, Nikapota A, O'Sullivan J, Parikh O, Peedell C, Protheroe A, Rudman SM, Shaffer R, Sheehan D, Simms M, Srihari N, Strebel R, Sundar S, Tolan S, Tsang D, Varughese M, Wagstaff J, Parmar MKB, James ND; STAMPEDE Investigators. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018 May 1;29(5):1235-1248. doi: 10.1093/annonc/mdy072.

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Responsible Party: Parker Institute for Cancer Immunotherapy
ClinicalTrials.gov Identifier: NCT03835533     History of Changes
Other Study ID Numbers: PICI0033
First Posted: February 8, 2019    Key Record Dates
Last Update Posted: November 18, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Parker Institute for Cancer Immunotherapy:
Metastatic Castration-resistant Prostate Cancer
Immunotherapy
Platform study
NKTR-214
Nivolumab
CDX-301
Poly-ICLC
INO-5151
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Poly I-C
Nivolumab
Carboxymethylcellulose Sodium
Poly ICLC
Antineoplastic Agents, Immunological
Antineoplastic Agents
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents