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

NCT03770455 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2018-1236
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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). Metastases must be radiographically evident by whole body bone scintigraphy or CT/MRI scan. 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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  8 Weeks, 6 months

Secondary Outcomes (3)

• PSA Progression-free Survival (PFS)

  pPFS will be assessed 12 months after enrollment of last subject.

• Radiographic Progression-free Survival (PFS)

  rPFS will be assessed 12 months after enrollment of last subject.

• Overall Survival (OS)

  Overall survival with be assessed at 3 years from time of enrollment of last study subject.

Study Arms (1)

Avelumab + 2nd generation ADT

EXPERIMENTAL

Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT

Drug: Avelumab; Drug: 2nd generation ADT (abiraterone or enzalutamide)

Interventions

Avelumab DRUG

Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT

Also known as: Bavencio

Avelumab + 2nd generation ADT

2nd generation ADT (abiraterone or enzalutamide) DRUG

2nd generation ADT (abiraterone or enzalutamide)

Avelumab + 2nd generation ADT

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male based on biological distinctions not self-representation. Subject must have prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Jodi Layton, MD: lead
• EMD Serono: collaborator

Study Sites (1)

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Related Publications (12)

• 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.

  PMID: 27429197 BACKGROUND

• 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.

  PMID: 26028255 BACKGROUND

• 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.

  PMID: 27013479 BACKGROUND

• 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.

  PMID: 23530095 BACKGROUND

• 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.

  PMID: 27433846 BACKGROUND

• 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.

  PMID: 20818862 BACKGROUND

• 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.

  PMID: 25255306 BACKGROUND

• 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.

  PMID: 28410865 BACKGROUND

• 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.

  PMID: 19097774 BACKGROUND

• 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.

  PMID: 26903579 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 36210487 DERIVED

MeSH Terms

Interventions

avelumab; abiraterone; enzalutamide

Limitations and Caveats

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.

Results Point of Contact

• Title: Jodi L. Layton, MD
• Organization: Tulane University School of Medicine

jlayton@tulane.edu

504-988-6121

Study Officials

• Jodi L Layton, MD

  Tulane University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: December 10, 2018
• Study Start: January 25, 2019
• Primary Completion: December 17, 2020
• Study Completion: January 7, 2021
• Last Updated: July 9, 2024
• Results First Posted: January 18, 2022

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 2022
• Access Criteria: To be determined pending publication

Locations

US (1)