Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)

Metastatic Castration-resistant Prostate Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02987543
• Other study ID #: D081DC00007
• Secondary ID: 2016-000300-28
• Status: Completed
• Phase: Phase 3
• Start date: February 6, 2017
• Est. completion date: February 15, 2023

Study information

• Verified date: September 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 387
• Est. completion date: February 15, 2023
• Est. primary completion date: June 4, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• olaparib
300 mg (2x 150 mg tablets) twice daily
• enzalutamide
160 mg (4 x 40 mg capsules) once daily
• abiraterone acetate
1,000 mg (4 x 250 mg tablets) once daily
• abiraterone acetate
1,000 mg (2 x 500 mg tablets) once daily
• enzalutamide
160 mg (4 x 40 mg tablets) once daily

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	La Rioja
Argentina	Research Site	Rosario
Australia	Research Site	Adelaide
Australia	Research Site	Box Hill
Australia	Research Site	Clayton
Australia	Research Site	Greenslopes
Australia	Research Site	Herston
Australia	Research Site	Macquarie University
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	Randwick
Australia	Research Site	Waratah
Austria	Research Site	Graz
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Austria	Research Site	Wien
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Curitiba
Brazil	Research Site	Florianópolis
Brazil	Research Site	Passo Fundo
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Ribeirao Preto
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo Andre
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Oakville	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Denmark	Research Site	Odense C
France	Research Site	BESANCON Cedex
France	Research Site	Bordeaux Cedex
France	Research Site	Caen
France	Research Site	Lille
France	Research Site	Lyon Cedex 08
France	Research Site	Marseille cedex 09
France	Research Site	Montpellier
France	Research Site	Paris
France	Research Site	Poitiers Cedex
France	Research Site	Saint Herblain
France	Research Site	Toulouse Cedex 09
France	Research Site	Vandoeuvre les Nancy
France	Research Site	Villejuif
Germany	Research Site	Bergisch Gladbach
Germany	Research Site	Berlin
Germany	Research Site	Bremen
Germany	Research Site	Duisburg
Germany	Research Site	Düsseldorf
Germany	Research Site	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Holzminden
Germany	Research Site	Jena
Germany	Research Site	Köln
Germany	Research Site	Magdeburg
Germany	Research Site	Nürnberg
Germany	Research Site	Nürtingen
Germany	Research Site	Tübingen
Germany	Research Site	Wuppertal
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Petach-Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Zerifin
Italy	Research Site	Ancona
Italy	Research Site	Arezzo
Italy	Research Site	Bari
Italy	Research Site	Brescia
Italy	Research Site	Meldola
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Trento
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Fukuoka
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kashihara-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kawagoe-shi
Japan	Research Site	Kita-gun
Japan	Research Site	Koto-ku
Japan	Research Site	Kyoto-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Mitaka-shi
Japan	Research Site	Miyazaki-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sakura-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Suita-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Hilversum
Netherlands	Research Site	Leiden
Netherlands	Research Site	Nijmegen
Netherlands	Research Site	Tilburg
Netherlands	Research Site	Zwolle
Norway	Research Site	Lørenskog
Spain	Research Site	Gerona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Oviedo
Spain	Research Site	Sevilla
Sweden	Research Site	Göteborg
Sweden	Research Site	Solna
Taiwan	Research Site	Changhua City
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan City
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Karsiyaka
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Romford
United Kingdom	Research Site	Sutton
United States	Research Site	Albany	New York
United States	Research Site	Anchorage	Alaska
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbus	Ohio
United States	Research Site	Duarte	California
United States	Research Site	Durham	North Carolina
United States	Research Site	Germantown	Tennessee
United States	Research Site	Jeffersonville	Indiana
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Myrtle Beach	South Carolina
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Orleans	Louisiana
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Salisbury	North Carolina
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Santa Barbara	California
United States	Research Site	Spokane	Washington
United States	Research Site	Springfield	Oregon
United States	Research Site	Syracuse	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Towson	Maryland
United States	Research Site	Tualatin	Oregon
United States	Research Site	Tucson	Arizona
United States	Research Site	Tucson	Arizona
United States	Research Site	Washington	District of Columbia
United States	Research Site	Wheeling	West Virginia

Sponsors (4)

Lead Sponsor	Collaborator
AstraZeneca	Foundation Medicine, Inc., Merck Sharp & Dohme LLC, Myriad Genetics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only	The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).	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	Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only	ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.	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	Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B	The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.	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	Time to Pain Progression - Cohort A Only	Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.	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).
Secondary	Overall Survival (OS) - Cohort A Only	Number of Participants with Overall Survival (OS) - Cohort A only.	Approximately 35 months after the first patient was randomised.

External Links

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