Metastatic Castration-resistant Prostate CancerPhase 2NCT03770455

Avelumab Plus 2nd-generation ADT in African American Subjects With mCRPC

A Phase 2 study testing Avelumab and 2nd generation ADT (abiraterone or enzalutamide) in people with Metastatic Castration-resistant Prostate Cancer, run by Jodi Layton, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

This is a nonrandomized, open-label trial of avelumab in subjects with metastatic castration-resistant prostate cancer (mCRPC) experiencing PSA or radiographic progression while receiving 2nd generation ADT (abiraterone / enzalutamide/ apalutamide or darolutamide). Read more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Metastatic Castration-resistant Prostate Cancer
What is being tested?: Avelumab and 2nd generation ADT (abiraterone or enzalutamide)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteUnited States
Study dates: 25 Jan 2019to 7 Jan 2021
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

Must be of African descent; Black or African American: A person having origins in any of the black racial groups of Africa. Terms such as "Haitian" or "Negro" can be used in addition to "Black or African American."
Be willing and able to provide written informed consent for the trial.
Be ≥18 years of age on day of signing informed consent.
Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology. Diagnosis must be stated in a pathology report.
Have evidence of metastatic disease as determined by CT/MRI scans and/or bone metastases by whole body bone scintigraphy. (Use MRI if CT is contraindicated, and for imaging of the brain if clinically indicated).
Have documented disease progression within 3 months of screening, as determined by the Investigator, by means of at least one of the following:

Show all 13Show fewer

PSA progression as defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each assessment where the PSA value at screening should be ≥ 2 ng/mL.
Radiographic disease progression in soft tissue or bone with or without PSA progression as determined by Recist 1.1 and/or PCWG3
Have ongoing androgen deprivation with serum testosterone < 50 ng/dL (< 2.0 nM). If the subject is currently being treated with Luteinising Hormone Releasing Hormone (LHRH) agonists or antagonists (for subjects who have not undergone an orchiectomy). This treatment must be continued throughout the study.
Be receiving and tolerating either abiraterone acetate, enzalutamide, apalutamide or darolutamide for at least 8 weeks prior to documented disease progression. Note: the 2nd generation ADT that the patient is currently progression on needs to be the first 2nd gen ADT used in the CRPC setting
Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Appendix D).
Male subjects of reproductive potential must agree practice abstinence from heterosexual activity OR use a highly effective method of contraception, starting at the time of informed consent and continue through 60 days after the last dose of study therapy (see section 6.1.1.)
Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.

Who cannot join

Is currently participating and receiving study therapy in a clinical trial, or has participated in a study of an investigational agent (and received study therapy or used an investigation device) within 4 weeks of the first dose of study treatment.
No more than one line of a 2nd generation ADT (abiraterone acetate /enzalutamide/ apalutamide/darolutamide) for mCRPC is permitted for study entry.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Note: the following are allowed: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intraarticular injection); b. systemic corticosteroids at physiological doses < 10mg/day of prednisone or equivalent; c. steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to mAbs administered more than 4 weeks earlier.
Has had >2 prior systemic chemotherapy agents for mCRPC Note: chemotherapy in the metastatic hormone sensitive prostate cancer (mHSPC) setting is allowed

Show all 21Show fewer

Prior surgery within 4 weeks of initiating study treatment Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to the first dose of trial treatment.
Has any additional malignancy that has required active treatment in the last 3 years.
Exceptions include: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or low-grade Ta or T1 urothelial carcinoma of that bladder that has undergone potentially curative therapy.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Has an active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
Has had prior organ transplantation including allogenic stem-cell transplantation.
Has an active infection requiring systemic therapy.
Has active, clinically significant Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Patients with well controlled HIV will be allowed to be enrolled into the study.
Has Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive).
Has received a live vaccine within 4 weeks of first dose of avelumab; live vaccines are prohibited throughout course of the trial. Inactivated vaccines are allowed.
Has known prior severe hypersensitivity to investigational product or component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.3 Grade > 3).
Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6months prior to enrollment), myocardial infarction (< 6months prior to enrollment), unstable angina, congestive heart failure (> New York Heart Association Classification Class II), or serious cardiac ventricular arrhythmia requiring medication.
Persisting toxicity related to prior therapy (NCI CTCAE v. 4.3 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, 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, immune 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

Tulane University School of Medicine
New Orleans, Louisiana, 70112

Other trials in United States

About this study

Official title: PDL-1 Inhibition With Avelumab and Concurrent Second-generation ADT in African Americans With Castrate-resistant Metastatic Prostate Cancer

Thirteen African American subjects will be enrolled into the initial cohort.

If at least one positive response (PSA decrease by >50% and or radiographic per RECIST 1.1) is found, the study will be expanded to accrue a total of 27 patients. The trial will be conducted in accordance with Good Clinical Practices.

Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and continue their previously started 2nd generation ADT (abiraterone or enzalutamide).

Treatment with avelumab will continue until documented confirmed disease progression, unacceptable AEs, intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the subject, subject discontinuation from the study, noncompliance with trial treatment or procedure requirements, subject receives 52 administrations of avelumab (approximately 2 years), or administrative reasons requiring the cessation of treatment.

After the end of treatment, each subject will be followed for 30 days for AE monitoring (serious AEs will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier). Subjects who discontinue treatment for reasons other than disease progression will remain on study and continue to undergo study-related disease assessments until documented disease progression, initiation of a new non-study prostate cancer treatment, withdrawal of consent, or becoming lost to follow-up. All subjects will enter survival follow up, and will be contacted at their regularly scheduled clinic visit, or by telephone approximately every 6 months, until death or withdrawal of consent or end of study.

Read the detailed description

Thirteen African American subjects will be enrolled into the initial cohort. If at least one positive response (PSA decrease by >50% and or radiographic per RECIST 1.1) is found, the study will be expanded to accrue a total of 27 patients. The trial will be conducted in accordance with Good Clinical Practices.

Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and continue their previously started 2nd generation ADT (abiraterone or enzalutamide).

All subjects will undergo radiographic imaging assessments and PSA assessments to evaluate response to treatment at regular intervals. On study imaging will be assessed every 12 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be adapted per the consensus guidelines of the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as described in Appendix A/B to account for the tumor progression patterns seen in bone metastases in prostate cancer. PSA will be obtained every 2 weeks with PSA progression assessed per PCWG3.

Adverse events (AEs) will be monitored throughout the trial and graded in severity according to the guidelines outlined in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Conditions: Metastatic Castration-resistant Prostate Cancer
Being tested: Avelumab, 2nd generation ADT (abiraterone or enzalutamide)

What participants receive

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

AvelumabDrug
Also called Bavencio
Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT
2nd generation ADT (abiraterone or enzalutamide)Drug
2nd generation ADT (abiraterone or enzalutamide)

Study groups in NCT03770455
Study group	Role	What they receive
Avelumab + 2nd generation ADT	Experimental	Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT Receives: Drug: Avelumab; Drug: 2nd generation ADT (abiraterone or enzalutamide)

What is being measured

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

Prostate-Specific Antigen (PSA) Response Greater Than or Equal to 50%
The primary endpoint is a PSA response at 8 weeks or greater from starting study treatment and with a minimum of 3 treatments administered.
A PSA response is defined as a ≥50% PSA decline at 8 weeks or greater from the time of starting study treatment. The two-stage minimax design of the study will be utilized to determine whether further investigation of the study drug is warranted.
Measured: 8 Weeks, 6 months

Secondary outcomes (3)

PSA Progression-free Survival (PFS)
PSA progression-free survival (pPFS) defined as the time from enrollment until PSA progression by Prostate Cancer Working Group 3 (PCWG3) or death, whichever occurs earlier. Subjects without pPFS at the time of data cut-off will be censored at the date of last adequate cancer assessment. PSA progression-free survival will be reported using Kaplan-Meier estimates, with 95% confidence interval for median time-to-event.
Measured: pPFS will be assessed 12 months after enrollment of last subject.
Radiographic Progression-free Survival (PFS)
Radiographic progression-free survival (rPFS) defined as the time from enrollment until radiographic progression by PCWG3 or death, whichever occurs earlier. Subjects without rPFS at the time of data cut-off will be censored at the date of last known to be alive. Radiographic progression-free survival will be reported using Kaplan-Meier estimates, with 95% confidence interval for median time-to-event.
Measured: rPFS will be assessed 12 months after enrollment of last subject.
Overall Survival (OS)
Overall survival (OS) defined as the time from enrollment until death on study. Subjects who are alive at the time of data cut-off will be censored at the date of last known to be alive. OS will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.
Measured: Overall survival with be assessed at 3 years from time of enrollment of last study subject.

Timeline

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

25 Jan 20197 Jan 2021

First posted10 Dec 2018
Study start25 Jan 2019
Primary completion17 Dec 2020
Study completion7 Jan 2021

Why it stopped: Early signs of progression and learned experience that the assumed time period between psa progression and radiographic progression was shorter than expected

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 (12)Papers the sponsor has linked to this study.
Other trials for Metastatic Castration-resistant 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: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03770455
Sponsor's protocol ID: 2018-1236
Status last verified: Jun 2024
First submitted: 5 Oct 2018
Last updated: 9 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: all collected IPD, all IPD that underlie results in a publication

Publications

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
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.
PubMed 26028255
Dominguez-Valentin M, Joost P, Therkildsen C, Jonsson M, Rambech E, Nilbert M. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urol. 2016 Mar 24;16:15. doi: 10.1186/s12894-016-0130-1.
PubMed 27013479
Raymond VM, Mukherjee B, Wang F, Huang SC, Stoffel EM, Kastrinos F, Syngal S, Cooney KA, Gruber SB. Elevated risk of prostate cancer among men with Lynch syndrome. J Clin Oncol. 2013 May 10;31(14):1713-8. doi: 10.1200/JCO.2012.44.1238. Epub 2013 Mar 25.
PubMed 23530095
Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, Beightol M, Morrissey C, Nghiem B, Cheng HH, Montgomery B, Walsh T, Casadei S, Berger M, Zhang L, Zehir A, Vijai J, Scher HI, Sawyers C, Schultz N, Kantoff PW, Solit D, Robson M, Van Allen EM, Offit K, de Bono J, Nelson PS. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016 Aug 4;375(5):443-53. doi: 10.1056/NEJMoa1603144. Epub 2016 Jul 6.
PubMed 27433846
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
Pritchard CC, Morrissey C, Kumar A, Zhang X, Smith C, Coleman I, Salipante SJ, Milbank J, Yu M, Grady WM, Tait JF, Corey E, Vessella RL, Walsh T, Shendure J, Nelson PS. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat Commun. 2014 Sep 25;5:4988. doi: 10.1038/ncomms5988.
PubMed 25255306
Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, Harmenberg U, McDermott DF, Choueiri TK, Richardet M, Tomita Y, Ravaud A, Doan J, Zhao H, Hardy H, George S. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Eur Urol. 2017 Sep;72(3):368-376. doi: 10.1016/j.eururo.2017.03.037. Epub 2017 Apr 12.
PubMed 28410865
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
Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.
PubMed 26903579
Sartor et al. Overall Survival Analysis of African American and Caucasian Patients Receiving Sipuleucel-T: Preliminary Data from the Proceed Registry. J Urol, Vol 197: 4, April 2017.
Hawkins CM, Barata PC, Cotogno P, Davis G, Jaeger E, Ledet E, Miller P, Lewis B, Sartor O, Layton J. Black Patients with Metastatic Castrate-Resistant Prostate Cancer Have a Shorter Time Interval Between PSA and Clinical Progression on Novel Hormonal Therapies plus Avelumab. Oncologist. 2023 Mar 17;28(3):276-e158. doi: 10.1093/oncolo/oyac203.
PubMed 36210487

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
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RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer

All Metastatic Castration-resistant Prostate Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: PDL-1 Inhibition With Avelumab and Concurrent Second-generation ADT in African Americans With Castrate-resistant Metastatic Prostate Cancer
ClinicalTrials.gov ID: NCT03770455
Acronym / sponsor ID: 2018-1236
Conditions: Metastatic Castration-resistant Prostate Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Early signs of progression and learned experience that the assumed time period between psa progression and radiographic progression was shorter than expected
Enrolment: 8 participants (actual)
Lead sponsor: Jodi Layton, MDUniversity, hospital or other
Collaborators: EMD Serono
Study start: 25 Jan 2019 (actual)
Primary completion: 17 Dec 2020 (actual)
Study completion: 7 Jan 2021 (actual)
First posted: 10 Dec 2018 (actual)
Results: Posted 18 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Thirteen African American subjects will be enrolled into the initial cohort.

Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and continue their previously started 2nd generation ADT (abiraterone or enzalutamide).

Detailed description

Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and continue their previously started 2nd generation ADT (abiraterone or enzalutamide).

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Avelumab + 2nd generation ADT	Experimental	Drug: Avelumab, Drug: 2nd generation ADT (abiraterone or enzalutamide)Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Must be of African descent; Black or African American: A person having origins in any of the black racial groups of Africa. Terms such as "Haitian" or "Negro" can be used in addition to "Black or African American."
Be willing and able to provide written informed consent for the trial.
Be ≥18 years of age on day of signing informed consent.
Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology. Diagnosis must be stated in a pathology report.
Have evidence of metastatic disease as determined by CT/MRI scans and/or bone metastases by whole body bone scintigraphy. (Use MRI if CT is contraindicated, and for imaging of the brain if clinically indicated).

Key exclusion criteria (21 listed)

Is currently participating and receiving study therapy in a clinical trial, or has participated in a study of an investigational agent (and received study therapy or used an investigation device) within 4 weeks of the first dose of study treatment.
No more than one line of a 2nd generation ADT (abiraterone acetate /enzalutamide/ apalutamide/darolutamide) for mCRPC is permitted for study entry.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Note: the following are allowed: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intraarticular injection); b. systemic corticosteroids at physiological doses < 10mg/day of prednisone or equivalent; c. steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to mAbs administered more than 4 weeks earlier.

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
AvelumabAlso: BavencioAvelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT	Drug	Avelumab + 2nd generation ADT
2nd generation ADT (abiraterone or enzalutamide)2nd generation ADT (abiraterone or enzalutamide)	Drug	Avelumab + 2nd generation ADT

Primary outcome

Prostate-Specific Antigen (PSA) Response Greater Than or Equal to 50%
Time frame: 8 Weeks, 6 months
The primary endpoint is a PSA response at 8 weeks or greater from starting study treatment and with a minimum of 3 treatments administered. A PSA response is defined as a ≥50% PSA decline at 8 weeks or greater from the time of starting study treatment. The two-stage minimax design of the study will be utilized to determine whether further investigation of the study drug is warranted.

3 secondary outcomes

PSA Progression-free Survival (PFS)
Time frame: pPFS will be assessed 12 months after enrollment of last subject.
Radiographic Progression-free Survival (PFS)
Time frame: rPFS will be assessed 12 months after enrollment of last subject.
Overall Survival (OS)
Time frame: Overall survival with be assessed at 3 years from time of enrollment of last study subject.

Results and safety

Results posted to the registry on 18 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Avelumab + 2nd Generation ADT	8	5

Primary outcome: Prostate-Specific Antigen (PSA) Response Greater Than or Equal to 50%

Time frame: 8 Weeks, 6 months

Population analysed: Study closed early due to safety concerns. None of the participants reached the 8 weeks time point pre-specified for this analysis and hence PSA response data were not collected.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year, 8 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Avelumab + 2nd Generation ADT	4 of 5 (80%)	4 of 5 (80%)	1 of 1

Limitations and caveats (from the sponsor): Study did not reach target number of participants needed to reach target power for statistically reliable results due to poor recruitment during Coronavirus Disease 2019 (COVID-19) pandemic and early termination of study. Study closed early due to safety concerns regarding rapid clinical progression of several participants, therefore, the secondary outcome measures were not analyzed and no data was reported for those outcome measures, so they were deleted from the study record.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27429197Graff 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.
Background: PubMed 26028255Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.
Background: PubMed 27013479Dominguez-Valentin M, Joost P, Therkildsen C, Jonsson M, Rambech E, Nilbert M. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urol. 2016 Mar 24;16:15. doi: 10.1186/s12894-016-0130-1.
Background: PubMed 23530095Raymond VM, Mukherjee B, Wang F, Huang SC, Stoffel EM, Kastrinos F, Syngal S, Cooney KA, Gruber SB. Elevated risk of prostate cancer among men with Lynch syndrome. J Clin Oncol. 2013 May 10;31(14):1713-8. doi: 10.1200/JCO.2012.44.1238. Epub 2013 Mar 25.
Background: PubMed 27433846Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, Beightol M, Morrissey C, Nghiem B, Cheng HH, Montgomery B, Walsh T, Casadei S, Berger M, Zhang L, Zehir A, Vijai J, Scher HI, Sawyers C, Schultz N, Kantoff PW, Solit D, Robson M, Van Allen EM, Offit K, de Bono J, Nelson PS. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016 Aug 4;375(5):443-53. doi: 10.1056/NEJMoa1603144. Epub 2016 Jul 6.
Background: PubMed 20818862Kantoff 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.
Background: PubMed 25255306Pritchard CC, Morrissey C, Kumar A, Zhang X, Smith C, Coleman I, Salipante SJ, Milbank J, Yu M, Grady WM, Tait JF, Corey E, Vessella RL, Walsh T, Shendure J, Nelson PS. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat Commun. 2014 Sep 25;5:4988. doi: 10.1038/ncomms5988.
Background: PubMed 28410865Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, Harmenberg U, McDermott DF, Choueiri TK, Richardet M, Tomita Y, Ravaud A, Doan J, Zhao H, Hardy H, George S. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Eur Urol. 2017 Sep;72(3):368-376. doi: 10.1016/j.eururo.2017.03.037. Epub 2017 Apr 12.
Background: PubMed 19097774Eisenhauer 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.
Background: PubMed 26903579Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.
BackgroundSartor et al. Overall Survival Analysis of African American and Caucasian Patients Receiving Sipuleucel-T: Preliminary Data from the Proceed Registry. J Urol, Vol 197: 4, April 2017.
Derived from this study: PubMed 36210487Hawkins CM, Barata PC, Cotogno P, Davis G, Jaeger E, Ledet E, Miller P, Lewis B, Sartor O, Layton J. Black Patients with Metastatic Castrate-Resistant Prostate Cancer Have a Shorter Time Interval Between PSA and Clinical Progression on Novel Hormonal Therapies plus Avelumab. Oncologist. 2023 Mar 17;28(3):276-e158. doi: 10.1093/oncolo/oyac203.
Individual participant dataSharing planned: Yes. all collected IPD, all IPD that underlie results in a publication

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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.

Jodi L Layton, MD principal investigator

Tulane University School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 13 inclusion and 21 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: stopped early, as of the sponsor's last update on 9 Jul 2024. 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 18 Jan 2022). 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?

Prostate-Specific Antigen (PSA) Response Greater Than or Equal to 50% (time frame: 8 Weeks, 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 NCT03770455, which also lists 12 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 9 Jul 2024.