Prostate CancerPhase 2PICK-NEPCNCT03179410
PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer
A Phase 2 study testing Avelumab in people with Prostate Cancer, run by Andrew J. Armstrong, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Avelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2018to 18 Dec 2020
- Phase
- Phase 2
- 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
- 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.
- 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.
- 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:
- 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).
- Measurable disease as defined by modified PCWG3 using iRECIST criteria
- 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.
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- Documented progressive metastatic CRPC based on at least one of the following criteria:
- 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.
- Soft-tissue progression based on new lesions or growth of existing soft tissue metastases.
- Progression of bone disease (evaluable disease) or (new bone lesion(s)) by bone scan.
- Castrate levels of serum total testosterone (<50 ng/dl) OR ongoing documented ADT unless pure small cell prostate cancer is present.
- 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.
- Patients should have received at least one line of approved chemotherapy and/or hormonal therapy
- Previous cytotoxic chemotherapy including cisplatin, carboplatin, oxaliplatin, etoposide, docetaxel, cabazitaxel, and gemcitabine is allowed, up to 3 prior regimens.
- Karnofsky performance status of 70 or higher.
- 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
- Age >18
- 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.
- Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
- Life expectancy of over 3 months as determined by treating physician.
Who cannot join
- 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.
- 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.
- Previous malignancy within 3 years other than non-melanomatous skin cancers or cancers of low malignant potential such as non-invasive urothelial carcinoma.
- Any other on-going chemotherapeutic, biologic, radiopharmaceutical, or investigational agent currently or within 28 days of Cycle 1 Day 1.
- 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.
- 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).
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- Prior organ transplantation including allogeneic stem-cell transplants.
- Active bacterial or viral infections requiring systemic therapy.
- Current active infections with HIV/AIDS, Hepatitis B, and Hepatitis C requiring treatment.
- Live virus vaccination within 4 weeks of the first dose of avelumab (inactivated vaccines are allowed).
- Known prior hypersensitivity to the investigational product or any component formulations, including known severe hypersensitivity reactions to monoclonal antibodies.
- 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.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
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.
- Conditions
- Prostate Cancer
- Being tested
- Avelumab
- Keywords
- metastatic castrate-resistant prostate cancer (mCRPC), neuroendocrine prostate cancer (NEPC)
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
10 mg/kg intravenously every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Neuroendocrine prostate cancer (NEPC) | Experimental | Subjects with neuroendocrine prostate cancer (NEPC). Avelumab will be administered intravenously at a dose of 10 mg/kg every 2 weeks. Receives: Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Overall Response as Determined by iRECIST
Overall response rate is determined by radiographic response assessment utilizing modified Prostate Cancer Working Group 3 (PCWG3) using Immune Response Evaluation Criteria In Solid Tumors Criteria (iRECIST 1.1). iRECIST is the modified RECIST 1.1 for immune-based therapeutics, to measure radiographic response rate in men with metastatic prostate cancer. Patients alive who had not progressed as of the last follow-up, had PFS censored at the last follow-up date. There are five categories overall responses:
iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 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 lesions iSD: immune stable disease in the absence of CR or PD iUPD: immune unconfirmed progressive disease when PD is unconfirmed NE: not evaluable
Measured: baseline to end of treatment (approximately 6 months)
Secondary outcomes (4)
Efficacy of PD-L1 Inhibition With Avelumab as Determined by RECIST1.1
Overall response rate is determined by radiographic response assessment utilizing Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1). Patients alive who had not progressed as of the last follow-up, had PFS censored at the last follow-up date. There are four overall response categories:
Complete Response (CR): disappearance of all target and non-target lesions Progressive Disease (PD): 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 lesions Stable Disease (SD): In the absence of CR and PD Unevaluable (NE)
Measured: baseline to end of treatment (approximately 6 months)
Radiographic Progression Free Survival (rPFS)
Radiographic progression free survival (rPFS) as determined by PCWG3 and RECISTS1.1 criteria. Radiographic progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1), 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 lesions. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median rPFS was estimated using a Kaplan-Meier curve.
Measured: baseline to end of treatment (approximately 6 months)
Overall Survival
Length of patient's life after starting study
Measured: Up to 23.5 months
Toxicity and Safety of PD-L1 Inhibition With Avelumab in Men With Metastatic Neuroendocrine-like Prostate Cancer
Number of Participants with Adverse Events
Measured: 28 days post-treatment (approximately 7 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2017
- Study start1 Feb 2018
- Primary completion9 Jan 2020
- Study completion18 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrew J. Armstrong, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andrew J. Armstrong, MD, Duke University
- Investigators
- Andrew Armstrong, MD, ScM, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03179410
- Sponsor's protocol ID
- Pro00080869
- Acronym
- PICK-NEPC
- Status last verified
- Feb 2021
- First submitted
- 5 Jun 2017
- Last updated
- 5 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Brown LC, Halabi S, Somarelli JA, Humeniuk M, Wu Y, Oyekunle T, Howard L, Huang J, Anand M, Davies C, Patel P, Staats J, Weinhold KJ, Harrison MR, Zhang T, George DJ, Armstrong AJ. A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer. Prostate Cancer Prostatic Dis. 2022 Apr;25(4):762-769. doi: 10.1038/s41391-022-00524-7. Epub 2022 Mar 15.
PubMed 35292724
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer
- ClinicalTrials.gov ID
- NCT03179410
- Acronym / sponsor ID
- PICK-NEPC / Pro00080869
- Conditions
- Prostate Cancer
- Keywords
- metastatic castrate-resistant prostate cancer (mCRPC), neuroendocrine prostate cancer (NEPC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Andrew J. Armstrong, MDUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 9 Jan 2020 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 7 Jun 2017 (actual)
- Results
- Posted 5 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neuroendocrine prostate cancer (NEPC) | Experimental | Drug: AvelumabSubjects with neuroendocrine prostate cancer (NEPC). Avelumab will be administered intravenously at a dose of 10 mg/kg every 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
- Measurable disease as defined by modified PCWG3 using iRECIST criteria
- 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.
- Documented progressive metastatic CRPC based on at least one of the following criteria:
- Castrate levels of serum total testosterone (<50 ng/dl) OR ongoing documented ADT unless pure small cell prostate cancer is present.
Key exclusion criteria (14 listed)
- 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.
- 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.
- Previous malignancy within 3 years other than non-melanomatous skin cancers or cancers of low malignant potential such as non-invasive urothelial carcinoma.
- Any other on-going chemotherapeutic, biologic, radiopharmaceutical, or investigational agent currently or within 28 days of Cycle 1 Day 1.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Avelumab10 mg/kg intravenously every 2 weeks | Drug | Neuroendocrine prostate cancer (NEPC) |
Primary outcome
Number of Participants With Overall Response as Determined by iRECIST
Time frame: baseline to end of treatment (approximately 6 months)
Overall response rate is determined by radiographic response assessment utilizing modified Prostate Cancer Working Group 3 (PCWG3) using Immune Response Evaluation Criteria In Solid Tumors Criteria (iRECIST 1.1). iRECIST is the modified RECIST 1.1 for immune-based therapeutics, to measure radiographic response rate in men with metastatic prostate cancer. Patients alive who had not progressed as of the last follow-up, had PFS censored at the last follow-up date. There are five categories overall responses: iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 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 lesions iSD: immune stable disease in the absence of CR or PD iUPD: immune unconfirmed progressive disease when PD is unconfirmed NE: not evaluable
4 secondary outcomes
Efficacy of PD-L1 Inhibition With Avelumab as Determined by RECIST1.1
Time frame: baseline to end of treatment (approximately 6 months)
Radiographic Progression Free Survival (rPFS)
Time frame: baseline to end of treatment (approximately 6 months)
Overall Survival
Time frame: Up to 23.5 months
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35292724Brown LC, Halabi S, Somarelli JA, Humeniuk M, Wu Y, Oyekunle T, Howard L, Huang J, Anand M, Davies C, Patel P, Staats J, Weinhold KJ, Harrison MR, Zhang T, George DJ, Armstrong AJ. A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer. Prostate Cancer Prostatic Dis. 2022 Apr;25(4):762-769. doi: 10.1038/s41391-022-00524-7. Epub 2022 Mar 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Armstrong, MD, ScM principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avelumab in people with Prostate Cancer, run by Andrew J. Armstrong, MD at 1 site 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 21 inclusion and 14 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 5 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 5 Mar 2021). 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 Overall Response as Determined by iRECIST (time frame: baseline to end of treatment (approximately 6 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 NCT03179410, which also lists 1 linked publication.
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 5 Mar 2021.