Clinical trial NCT02987543: Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)
Official title: A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (PROfound)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: metastatic castration-resistant prostate cancer (mCRPC)
homologous recombination repair (HRR)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
name: Foundation Medicine
name: Myriad Genetics, Inc.
First posted: 2016-12-09
Enrollment: 387
Sex: MALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of olaparib versus enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have homologous recombination repair gene mutations.

Detailed description: This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair (HRR) pathway. Subjects will be divided into two cohorts based on HRR gene mutation status.

Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of enzalutamide or abiraterone acetate) into the trial.

Eligibility criteria: Inclusion criteria

1. Histologically confirmed diagnosis of prostate cancer.
2. Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate and/or enzalutamide) for the treatment of metastatic prostate cancer and/or CRPC .
4. Ongoing therapy with LHRH analog or bilateral orchiectomy.
5. Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
6. Qualifying HRR mutation in tumor tissue.

Exclusion criteria

1. Any previous treatment with PARP inhibitor, including olaparib.
2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy, except if for non-prostate cancer indication and last dose \> 5 years prior to randomization.
3. Other malignancy (including MDS and MGUS) within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥5 years.
4. Subjects with known brain metastases.

Primary outcomes:
measure: Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only
timeFrame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only
timeFrame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
measure: Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B
timeFrame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
measure: Time to Pain Progression - Cohort A Only
timeFrame: Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
measure: Overall Survival (OS) - Cohort A Only
timeFrame: Approximately 35 months after the first patient was randomised.
Other outcomes:
Locations:
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country: United States
facility: Research Site
state: Alaska
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
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state: Arizona
city: Duarte
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state: California
city: San Diego
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state: District of Columbia
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city: Barretos
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city: Chicoutimi
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city: Montreal
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city: Montreal
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city: Odense C
country: Denmark
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city: BESANCON Cedex
country: France
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city: Bordeaux Cedex
country: France
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city: Lille
country: France
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city: Lyon Cedex 08
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city: Vandoeuvre les Nancy
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country: Germany
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city: Ramat Gan
country: Israel
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country: Israel
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city: Ancona
country: Italy
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city: Arezzo
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city: Brescia
country: Italy
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city: Meldola
country: Italy
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city: Milano
country: Italy
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city: Milano
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city: Modena
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city: Napoli
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city: Trento
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city: Bunkyo-ku
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Shinjuku-ku
country: Japan
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city: Suita-shi
country: Japan
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city: Sunto-gun
country: Japan
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city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
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city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
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city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Amsterdam
country: Netherlands
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city: Hilversum
country: Netherlands
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city: Leiden
country: Netherlands
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city: Nijmegen
country: Netherlands
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city: Tilburg
country: Netherlands
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city: Zwolle
country: Netherlands
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city: Lørenskog
country: Norway
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city: Gerona
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Malaga
country: Spain
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city: Oviedo
country: Spain
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city: Sevilla
country: Spain
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city: Göteborg
country: Sweden
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city: Solna
country: Sweden
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city: Changhua City
country: Taiwan
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city: Kaohsiung
country: Taiwan
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city: Kaohsiung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Tainan
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taoyuan City
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
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city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
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city: Istanbul
country: Turkey
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city: Karsiyaka
country: Turkey
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Romford
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: The Institute of Cancer Research, United Kingdom
name: Johann de Bono, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University, United States of America
name: Maha Hussain, M.D., FACP, FASCO
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roubaud G, Ozguroglu M, Penel N, Matsubara N, Mehra N, Kolinsky MP, Procopio G, Feyerabend S, Joung JY, Gravis G, Nishimura K, Gedye C, Padua C, Shore N, Thiery-Vuillemin A, Saad F, van Alphen R, Carducci MA, Desai C, Brickel N, Poehlein C, Del Rosario P, Fizazi K. Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study. Eur J Cancer. 2022 Jul;170:73-84. doi: 10.1016/j.ejca.2022.04.016. Epub 2022 May 19.
citation: Matsubara N, Nishimura K, Kawakami S, Joung JY, Uemura H, Goto T, Kwon TG, Sugimoto M, Kato M, Wang SS, Pang ST, Chen CH, Fujita T, Nii M, Shen L, Dujka M, Hussain M, de Bono J. Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Jpn J Clin Oncol. 2022 May 5;52(5):441-448. doi: 10.1093/jjco/hyac015.
citation: Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. doi: 10.1016/S1470-2045(22)00017-1. Epub 2022 Feb 11.
citation: Hussain M, Corcoran C, Sibilla C, Fizazi K, Saad F, Shore N, Sandhu S, Mateo J, Olmos D, Mehra N, Kolinsky MP, Roubaud G, Ozguroglu M, Matsubara N, Gedye C, Choi YD, Padua C, Kohlmann A, Huisden R, Elvin JA, Kang J, Adelman CA, Allen A, Poehlein C, de Bono J. Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib). Clin Cancer Res. 2022 Apr 14;28(8):1518-1530. doi: 10.1158/1078-0432.CCR-21-3940.
citation: Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Ozguroglu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. doi: 10.1056/NEJMoa2022485. Epub 2020 Sep 20.
citation: de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. doi: 10.1056/NEJMoa1911440. Epub 2020 Apr 28.