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PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer (PICK-NEPC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03179410
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : March 29, 2019
Information provided by (Responsible Party):
Andrew J. Armstrong, MD, Duke University

Tracking Information
First Submitted Date  ICMJE June 5, 2017
First Posted Date  ICMJE June 7, 2017
Last Update Posted Date March 29, 2019
Actual Study Start Date  ICMJE February 1, 2018
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2017)
Efficacy of PD-L1 inhibition with avelumab as determined by iRECIST [ Time Frame: baseline to end of treatment (approximately 6 months) ]
Overall response rate as determined by a modified PCWG3 using iRECIST radiographic response
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03179410 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2017)
  • Efficacy of PD-L1 inhibition with avelumab as determined by RECIST1.1 [ Time Frame: baseline to end of treatment (approximately 6 months) ]
    Overall response rate as determined by PCWG3 using RECIST1.1 radiographic response
  • Radiographic progression free survival (rPFS) [ Time Frame: baseline to end of treatment (approximately 6 months) ]
    rPFS as determined by a modified PCWG3 with both RECISTS1.1 and iRECIST criteria
  • Overall survival [ Time Frame: 3 years ]
    Number and percent of participants that are alive
  • Toxicity and safety of PD-L1 inhibition with avelumab in men with metastatic neuroendocrine-like prostate cancer [ Time Frame: 28 days post-treatment (approximately 7 months) ]
    Number and Percent of Participants with Adverse Events
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer
Official Title  ICMJE PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer
Brief Summary The purpose of this study is to assess the safety and efficacy of avelumab in patients with metastatic neuroendocrine-like prostate cancer. Eligible men will be started on avelumab every 2 weeks and will stay on therapy until progression or intolerable side effects. The central hypothesis is that PD-L1 inhibition with avelumab will be efficacious based on radiographic responses in a subset of men with metastatic neuroendocrine-like prostate cancer and be reasonably well tolerated, meeting criteria for further study in larger phase 2 and 3 trials based on meeting pre-specified efficacy rates and prolonged PFS in some men.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE Drug: Avelumab
10 mg/kg intravenously every 2 weeks
Study Arms  ICMJE Experimental: Neuroendocrine prostate cancer (NEPC)
Subjects with neuroendocrine prostate cancer (NEPC). Avelumab will be administered intravenously at a dose of 10 mg/kg every 2 weeks.
Intervention: Drug: Avelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 6, 2017)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Neuroendocrine-like prostate cancer, based on histology OR based on clinical presentation as defined by meeting one of the two below criteria. All subjects must submit their primary tumor or metastatic biopsy pathology specimens to the Duke Cancer Institute where they will be centrally reviewed by Duke Pathology. Central Duke pathologic review is not required for screening but rather for confirmation of histologic subtype. Local pathologic review is sufficient for eligibility determination.

    1. Criterion 1: Presence of 1 of 3 histologically proven diagnoses: 1) Primary small cell carcinoma of the prostate, defined by classic histologic features such as small tumor cells with scanty cytoplasm, darkly stained nuclei with homogeneous chromatin pattern. The tumor cells do not form glandular structure but grow as solid sheets with frequent mitotic figures and necrosis; 2) Intermediate atypical carcinoma of the prostate, which has histologic features distinct from small cell carcinoma or adenocarcinoma. The tumor grows as solid sheets or vague glandular structures. The tumor cells have moderate amounts of cytoplasm and centrally located, round and regular nuclei with fine, granular and homogeneous chromatin. Mitosis and necrosis are absent; 3) mixed histology tumors of the prostate, containing both adenocarcinoma and neuroendocrine or small cell components.
    2. Criterion 2: Presence of histologically proven adenocarcinoma of the prostate without any sign of neuroendocrine or small cell histology that is radiographically progressing despite castrate levels of testosterone (<50 ng/mL) with the following poor risk features:

    i. Prior progression despite therapy with either abiraterone acetate and/or enzalutamide ii. At least one of the following: 1) Liver metastases; 2) Bulky radiographic progression (≥2 cm short axis lymph nodes or ≥1 cm long axis visceral metastases) combined with low serum PSA (<10ng/mL); 3) High serum LDH (>1X upper limit of normal).

  2. Measurable disease as defined by modified PCWG3 using iRECIST criteria
  3. Available tumor tissue for pathologic review and correlative studies. Tumor tissue (localized or metastatic) does not need to be received but rather identified and available (slides and/or blocks) to be sent to Duke.
  4. Documented progressive metastatic CRPC based on at least one of the following criteria:

    1. PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL. Note: If confirmed rise is the only indication of progression, a minimal starting value of 1.0 ng/mL is acceptable, unless pure small-cell carcinoma.
    2. Soft-tissue progression based on new lesions or growth of existing soft tissue metastases.
    3. Progression of bone disease (evaluable disease) or (new bone lesion(s)) by bone scan.
  5. Castrate levels of serum total testosterone (<50 ng/dl) OR ongoing documented ADT unless pure small cell prostate cancer is present.
  6. Previous use of radiation to metastatic site(s) at any time prior to enrollment is allowed, provided that this site is not the only measurable disease present or unless that solitary site is progressing following radiation.
  7. Patients should have received at least one line of approved chemotherapy and/or hormonal therapy
  8. Previous cytotoxic chemotherapy including cisplatin, carboplatin, oxaliplatin, etoposide, docetaxel, cabazitaxel, and gemcitabine is allowed, up to 3 prior regimens.
  9. Karnofsky performance status of 70 or higher.
  10. Acceptable initial laboratory values within 14 days of Cycle 1 Day 1 according to the below table:

    ANC ≥ 1500/µl Hemoglobin ≥ 9.0 g/dL(prior transfusion permitted) Platelet count ≥ 100,000/µl Creatinine ≤ 2.0 x the institutional upper limit of normal (ULN) OR creatinine clearance >30 ml/min Potassium ≥ 3.5 mmol/L (within institutional normal range) Bilirubin ≤ 1.5 x ULN (unless documented Gilbert's disease) SGOT (AST) ≤ 2.5x ULN, or <5x ULN in patients with documented liver metastases SGPT (ALT) ≤ 2.5x ULN or <5x ULN in patients with documented liver metastases

  11. Age >18
  12. Highly effective contraception for male subjects with childbearing potential throughout the study and for at least 60 days after last avelumab treatment administration if the risk of conception exists.
  13. Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
  14. Life expectancy of over 3 months as determined by treating physician.

Exclusion Criteria:

  1. Prior usage of PD-1 inhibitors, programed-death ligand 1 and/or 2 inhibitors, CTLA-4 inhibitors including but not limited to ipilimumab, nivolumab, avelumab, durvalumab, tremelimumab, and pembrolizumab.
  2. Active on-going immunologic or autoimmune disease including but not limited to systemic or cutaneous lupus erythematosus, cutaneous psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, sicca syndrome, polymyalgia rheumatica, polyarteritis nodosa, granulomatous polyangiitis, microscopic polyangiitis, polyarteritis nodosa, temporal arteritis, giant cell arteritis, dermatomyositis, Kawasaki disease.
  3. Previous malignancy within 3 years other than non-melanomatous skin cancers or cancers of low malignant potential such as non-invasive urothelial carcinoma.
  4. Any other on-going chemotherapeutic, biologic, radiopharmaceutical, or investigational agent currently or within 28 days of Cycle 1 Day 1.
  5. Prior use of abiraterone and other hormonal agents used to treat prostate cancer are permitted but abiraterone acetate should be stopped prior to study treatment initiation.
  6. Current usage of immunosuppressant medication except for a) intranasal, inhaled, and topical corticosteroids and b) systemic corticosteroids equivalent to ≤ 10 mg/day of prednisone, c) steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication).
  7. Prior organ transplantation including allogeneic stem-cell transplants.
  8. Active bacterial or viral infections requiring systemic therapy.
  9. Current active infections with HIV/AIDS, Hepatitis B, and Hepatitis C requiring treatment.
  10. Live virus vaccination within 4 weeks of the first dose of avelumab (inactivated vaccines are allowed).
  11. Known prior hypersensitivity to the investigational product or any component formulations, including known severe hypersensitivity reactions to monoclonal antibodies.
  12. Clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  13. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, Grade 2 anemia, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  14. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julia Rasmussen, MS, RN, BSN 919-681-1030
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03179410
Other Study ID Numbers  ICMJE Pro00080869
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Andrew J. Armstrong, MD, Duke University
Study Sponsor  ICMJE Andrew J. Armstrong, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew Armstrong, MD, ScM Duke University
PRS Account Duke University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP