AzTrials
AzTrials

Metastatic Castration-resistant Prostate CancerPhase 1PORTERNCT03835533

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

A Phase 1 study testing NKTR-214 (Cohort A), Nivolumab (Cohort A, B and C) and Stereotactic body radiation therapy (SBRT) (Cohort B) in people with Metastatic Castration-resistant Prostate Cancer, run by Parker Institute for Cancer Immunotherapy at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
NKTR-214 (Cohort A), Nivolumab (Cohort A, B and C) and Stereotactic body radiation therapy (SBRT) (Cohort B)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
6 sitesUnited States
Study dates
21 Jun 2019to 3 Oct 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Metastatic castration resistant prostate cancer with castrate-level testosterone (< 50 ng/dL) at screening.
  • Disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
  • Provide fresh pre-treatment core needle or incisional biopsy of a metastatic tumor lesion not previously irradiated. Fine needle aspiration is not acceptable.
  • 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.
  • For all participants, in addition to fresh pre-treatment biopsy, consent for archival tissue is required.
  • Must be willing to undergo tumor biopsy(ies) on treatment, if medically feasible.
Show all 15Show fewer
  • Have received and progressed on prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).
  • Participants must discontinue antiandrogen therapy (ie, bicalutamide, flutamide, nilutamide) at least 4-6 weeks prior to registration with no evidence of prostate-specific antigen (PSA) decline after washout.
  • Bicalutamide: Washout period at least 6 weeks
  • Flutamide and nilutamide: Washout period at least 4 weeks
  • Participants must discontinue therapies for mCRPC for 5 half-lives or 28 days, whichever is shorter.
  • Participants will remain on gonadotropin-releasing hormone (GnRH) agents throughout this study.
  • Prior chemotherapy is allowed if no progression of disease on chemotherapy as defined by PCWG3-modified RECIST 1.1.
  • Prior treatment with sipuleucel-T, radium-223, or poly ADP ribose polymerase (PARP) inhibitor (eg, olaparib) is allowed.
  • Tissue biopsy may be performed during washout period.

Who cannot join

  • 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.
  • 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.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Angeles Clinic

    Los Angeles, California, 90025

  • Mount Sinai

    New York, New York, 10029

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of California San Francisco

    San Francisco, California, 94158

Other trials in United States

About this study

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

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).

Read the 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.

Being tested
NKTR-214 (Cohort A), Nivolumab (Cohort A, B and C), Stereotactic body radiation therapy (SBRT) (Cohort B), CDX-301 (Cohort B and C), Poly-ICLC (Cohort B)
Keywords
Metastatic Castration-resistant Prostate Cancer, Immunotherapy, Platform study, NKTR-214, Nivolumab, CDX-301, Poly-ICLC, INO-5151

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NKTR-214 (Cohort A)Drug

    NKTR-214 will be administered intravenously every 3 weeks for up to 2 years

  • Nivolumab (Cohort A, B and C)Drug

    Also called Opdivo

    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.

  • Stereotactic body radiation therapy (SBRT) (Cohort B)Radiation

    Radiation therapy will be administered at 30 - 50 Gy in 1 - 5 doses, starting on Day 1 or 2 of Cycle 1

  • CDX-301 (Cohort B and C)Drug

    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.

  • Poly-ICLC (Cohort B)Drug

    Poly-ICLC will be administered intramuscularly twice weekly for 3 weeks starting on Day 1 of Cycle 1

  • INO-5151 (Cohort C)Drug

    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

  • Cellectra 2000Device

    Electroporation device

Study groups in NCT03835533
Study groupRoleWhat they receive
Cohort A: NKTR-214 + NivolumabExperimentalNot described
Receives: Drug: NKTR-214 (Cohort A); Drug: Nivolumab (Cohort A, B and C)
Cohort B: SBRT + CDX-301 + Poly-ICLC + NivolumabExperimentalNot described
Receives: 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)
Cohort C: CDX-301 + INO-5151 + NivolumabExperimentalNot described
Receives: Drug: Nivolumab (Cohort A, B and C); Drug: CDX-301 (Cohort B and C); Drug: INO-5151 (Cohort C); Device: Cellectra 2000

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

    An AE is any event that either occurs after the initiation of study drug, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, regardless of its relation to the drug. An SAE is any AE that suggests a significant hazard, contraindication, side effect, or untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

    Investigators recorded AEs during each participant interaction. Prior to initiation of study drug, only SAEs that were related to a protocol-mandated intervention were recorded.

    The AE row includes all participants who experienced at least one AE, including SAEs.

    Measured: For AEs, from initiation of study drug through 100 days after last dose, up to 24 months. For SAEs, from signing informed consent (prior to Screening) through 100 days after last dose, up to 24 months.

Secondary outcomes (5)

  1. Composite Response Rate (CRR)

    CRR is a composite endpoint where response is defined as a participant meeting at least one of the following:

    1. circulating tumor cells (CTC) change from unfavorable (≥ 5 cells/7.5 mL of blood) to favorable (<= 4 cells/7.5 mL of blood);
    2. ≥ 50% reduction in Prostate-Specific Antigen (PSA) from baseline, with a repeat assessment confirming the results at least 3 weeks later;
    3. Per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; >=30% decrease in the sum of the longest diameter of target lesions). A repeat tumor assessment must confirm the CR/PR results at least 3 weeks later.

    Measured: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

  2. Disease Control Rate (DCR)

    Per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a complete response (CR) is defined as disappearance of all target and non-target lesions and a partial response (PR) as a >=30% decrease in the sum of the longest diameter of target lesions. A repeat tumor assessment must confirm the CR/PR results at least 3 weeks later. DCR = CR + PR + stable disease lasting at least 6 months.

    Measured: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

  3. Radiographic Progression-free Survival (rPFS)

    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). Per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1, radiographic progression is defined using 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 non-bone lesions, or at least 2 new bone lesions relative to the first post-treatment scan that are confirmed on a subsequent scan.

    rPFS and confidence intervals were estimated using the Kaplan-Meier method.

    Measured: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

  4. Overall Survival (OS)

    Defined as the time from initiation of study invention until death due to any cause. OS and confidence intervals were estimated using the Kaplan-Meier method.

    Measured: From initiation of study drug until death due to any cause, up to 2.5 years

  5. Overall Survival (OS) at 12 Months

    Defined as the overall survival probability at 12 months, calculated using the Kaplan-Meier method.

    Measured: At 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2019
  2. Study start21 Jun 2019
  3. Primary completion3 Oct 2022
  4. Study completion3 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03835533
Sponsor's protocol ID
PICI0033
Acronym
PORTER
Status last verified
Oct 2023
First submitted
7 Feb 2019
Last updated
12 Apr 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin 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, Valdes-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.

    PubMed 23945592

  • Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, Ganju V, Polikoff J, Saad F, Humanski P, Piulats JM, Gonzalez Mella P, Ng SS, Jaeger D, Parnis FX, Franke FA, Puente J, Carvajal R, Sengelov L, McHenry MB, Varma A, van den Eertwegh AJ, Gerritsen W. Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer. J Clin Oncol. 2017 Jan;35(1):40-47. doi: 10.1200/JCO.2016.69.1584. Epub 2016 Oct 31.

    PubMed 28034081

  • Di Lorenzo G, Buonerba C, Kantoff PW. Immunotherapy for the treatment of prostate cancer. Nat Rev Clin Oncol. 2011 May 24;8(9):551-61. doi: 10.1038/nrclinonc.2011.72.

    PubMed 21606971

  • Drake CG. Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol. 2010 Aug;10(8):580-93. doi: 10.1038/nri2817.

    PubMed 20651745

  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

    PubMed 19097774

  • Flammiger A, Bayer F, Cirugeda-Kuhnert A, Huland H, Tennstedt P, Simon R, Minner S, Bokemeyer C, Sauter G, Schlomm T, Trepel M. Intratumoral T but not B lymphocytes are related to clinical outcome in prostate cancer. APMIS. 2012 Nov;120(11):901-8. doi: 10.1111/j.1600-0463.2012.02924.x. Epub 2012 Jul 4.

    PubMed 23009114

  • Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, Zhao H, Chen J, Chen H, Efstathiou E, Troncoso P, Allison JP, Logothetis CJ, Wistuba II, Sepulveda MA, Sun J, Wargo J, Blando J, Sharma P. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med. 2017 May;23(5):551-555. doi: 10.1038/nm.4308. Epub 2017 Mar 27.

    PubMed 28346412

  • Graff JN, Alumkal JJ, Drake CG, Thomas GV, Redmond WL, Farhad M, Cetnar JP, Ey FS, Bergan RC, Slottke R, Beer TM. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016 Aug 16;7(33):52810-52817. doi: 10.18632/oncotarget.10547.

    PubMed 27429197

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.

    PubMed 20818862

  • Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengelov L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR; CA184-043 Investigators. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):700-12. doi: 10.1016/S1470-2045(14)70189-5. Epub 2014 May 13.

    PubMed 24831977

  • Lee P, Gujar S. Potentiating prostate cancer immunotherapy with oncolytic viruses. Nat Rev Urol. 2018 Apr;15(4):235-250. doi: 10.1038/nrurol.2018.10. Epub 2018 Feb 13.

    PubMed 29434366

  • Lopez-Bujanda Z, Drake CG. Myeloid-derived cells in prostate cancer progression: phenotype and prospective therapies. J Leukoc Biol. 2017 Aug;102(2):393-406. doi: 10.1189/jlb.5VMR1116-491RR. Epub 2017 May 26.

    PubMed 28550116

  • Martin AM, Nirschl TR, Nirschl CJ, Francica BJ, Kochel CM, van Bokhoven A, Meeker AK, Lucia MS, Anders RA, DeMarzo AM, Drake CG. Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance. Prostate Cancer Prostatic Dis. 2015 Dec;18(4):325-32. doi: 10.1038/pcan.2015.39. Epub 2015 Aug 11.

    PubMed 26260996

  • McNeel DG, Bander NH, Beer TM, Drake CG, Fong L, Harrelson S, Kantoff PW, Madan RA, Oh WK, Peace DJ, Petrylak DP, Porterfield H, Sartor O, Shore ND, Slovin SF, Stein MN, Vieweg J, Gulley JL. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma. J Immunother Cancer. 2016 Dec 20;4:92. doi: 10.1186/s40425-016-0198-x. eCollection 2016.

    PubMed 28031820

  • Miller AM, Lundberg K, Ozenci V, Banham AH, Hellstrom M, Egevad L, Pisa P. CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol. 2006 Nov 15;177(10):7398-405. doi: 10.4049/jimmunol.177.10.7398.

    PubMed 17082659

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NKTR-214 (Cohort A), Nivolumab (Cohort A, B and C) and Stereotactic body radiation therapy (SBRT) (Cohort B) in people with Metastatic Castration-resistant Prostate Cancer, run by Parker Institute for Cancer Immunotherapy at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) (time frame: For AEs, from initiation of study drug through 100 days after last dose, up to 24 months. For SAEs, from signing informed consent (prior to Screening) through 100 days after last dose, up to 24 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03835533, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in