Clinical trial; Enzalutamide; TalazoparibEnsayo clínico; Enzalutamida; TalazoparibAssaig clínic; Enzalutamida; TalazoparibWhat is this summary about?
This summary describes the design of an ongoing research study (also known as a clinical trial) called TALAPRO-2. The TALAPRO-2 trial is testing the combination of two medicines called talazoparib and enzalutamide as a first treatment in adult men with metastatic castration-resistant prostate cancer. The study began in December 2017 and has enrolled 1037 adult men with metastatic castration-resistant prostate cancer from 26 countries.
What is metastatic castration-resistant prostate cancer?
Metastatic castration-resistant prostate cancer is a type of cancer that has advanced beyond the prostate and continues to grow even when testosterone levels in the blood are suppressed.
Which medicines are being tested?
The combination of talazoparib plus enzalutamide will be compared with enzalutamide plus placebo. Enzalutamide is approved to treat men with prostate cancer. Talazoparib is not approved to treat men with prostate cancer. A placebo does not contain any active ingredients and is also known as a sugar pill.
What are the aims of the TALAPRO-2 trial?
The TALAPRO-2 trial will find out if combining talazoparib with enzalutamide increases the length of time the men in the study live without their cancer getting worse compared with enzalutamide plus placebo. The study will also measure how long men in the study live and any side effects the men have while they are taking the study medicines. Researchers are also testing the DNA from the tumor cells of all men in the study to find out if they have faulty DNA repair genes.
Clinical Trial Registration: NCT0339519 (ClinicalTrials.gov

Agarwal, Neeraj

Azad, Arun

Carles Galceran, Joan

Dunshee, Curtis

Fay, Andre P

Shore, Neal

Future Oncology

English

Scientia, Dipòsit d’Informació Digital del Departament de Salut

part of10.2217/fon-2022-0389 © 2022 The AuthorsEnzalutamide: (EN-zuh-LOO-tuh-mide)Talazoparib: (tal-a-ZOE-pa-rib) Plain Language Summary of PublicationFirst draft submitted: 14 April 2022; Accepted for publication: 18 July 2022; Published online: 11 August 2022Plain language summary of the design  of the TALAPRO-2 study comparing  talazoparib and enzalutamide versus  enzalutamide and placebo in men with  metastatic castration-resistant prostate cancerNeeraj Agarwal¹, Arun Azad², Neal D Shore³, Joan Carles⁴, Andre P Fay⁵, Curtis Dunshee⁶, Lawrence Ivan Karsh⁷, Maria Luisa Paccagnella⁸,  Nicola Di Santo⁹, Mohamed Elmeliegy¹⁰, Xun Lin¹⁰, Akos Czibere¹¹ & Karim Fizazi¹²¹Huntsman Cancer Institute (NCI-CCC) at the University of Utah, Salt Lake City, UT, USA; ²Peter MacCallum Cancer Centre, Melbourne, Australia; ³Carolina Urologic Research Center, Myrtle Beach, SC, USA; ⁴Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, Spain; ⁵PUCRS School of Medicine Grupo Oncoclínicas, Porto Alegre, Brazil; ⁶Urological Associates of Southern Arizona, Tucson, AZ, USA; ⁷The Urology Center of Colorado, Denver, CO, USA; ⁸Pfizer Inc., Groton, CT, USA; ⁹Pfizer Inc., Durham, NC, USA;  ¹⁰Pfizer Inc., La Jolla, CA, USA; ¹¹Pfizer Inc., Cambridge, MA, USA; ¹²Institut Gustave Roussy, University of Paris-Saclay, Villejuif, FranceSummaryWhat is this summary about?This summary describes the design of an ongoing research study (also known as a clinical trial) called TALAPRO-2. The TALAPRO-2 trial is testing the combination of two medicines called talazoparib and enzalutamide as a first treatment in adult men with metastatic castration-resistant prostate cancer. The study began in December 2017 and has enrolled 1037 adult men with metastatic castration-resistant prostate cancer from 26 countries.What is metastatic castration-resistant prostate cancer?Metastatic castration-resistant prostate cancer is a type of cancer that has advanced beyond the prostate and continues to grow even when testosterone levels in the blood are suppressed. Which medicines are being tested?The combination of talazoparib plus enzalutamide will be compared with enzalutamide plus placebo. Enzalutamide is approved to treat men with prostate cancer. Talazoparib is not approved to treat men with prostate cancer. A placebo does not contain any active ingredients and is also known as a sugar pill. What are the aims of the TALAPRO-2 trial?The TALAPRO-2 trial will find out if combining talazoparib with enzalutamide increases the length of time the men in the study live without their cancer getting worse compared with enzalutamide plus placebo. The study will also measure how long men in the study live and any side effects the men have while they are taking the study medicines. Researchers are also testing the DNA from the tumor cells of all men in the study to find out if they have faulty DNA repair genes.Who is this article for?Where can I find the original article on which this summary is based?You can read the original article published in the journal Future Oncology for free at: https://www.futuremedicine.com/doi/10.2217/fon-2021-0811This summary was written by the authors of the original article to help patients and their caregivers, as well as health professionals, better understand the 2-part design of the TALAPRO-2 study.How to say (double-click on the icon to play sound)...ISSN 1479-6694Future Oncol. (2022) 18(27), 2979–2986 2979Plain Language Summary of Publication Agarwal, Azad, Shore and co-authorsfuture science groupWhat is metastatic castration-resistant prostate cancer?Castration-ResistantCan grow despite the  lower level of  testosterone in the bloodProstate cancer is one of the most common cancers in men. It forms in the tissues of the prostate, a male reproductive gland found below the bladder.Most prostate cancers need male sex hormones (also called androgens), such as testosterone, for them to grow.• Hormones work by carrying messages from one part of the body to another.Lowering testosterone levels in the blood is a common treatment for prostate cancer. • This may be done through surgery to remove the testicles (known as surgical castration) or testosterone suppression therapy (known as chemical castration). – Testosterone suppression therapy includes medications that lower the production of testosterone in the testicles.• Prostate cancer that stops growing or shrinks when treated with medicines that lower testosterone levels in the blood is called castration-sensitive prostate cancer. • In some men, surgical or chemical castration may work at first and later stop working. For other men, it may not work at all. In both cases, this type of cancer is called castration-resistant prostate cancer. – If the cancer does not respond to treatments that lower testosterone levels in the blood and it has spread beyond the prostate to other sites in the body, it is known as metastatic castration-resistant prostate cancer (also called mCRPC for short). MetastaticCancer that has spread  to other sites in  the bodym CRProstate CancerPCmCRPCFuture Oncol. (2022) 18(27)2980TALAPRO-2 study on metastatic castration-resistant prostate cancer Plain Language Summary of Publication future science group www.futuremedicine.comWhat is the role of DNA damage in prostate cancer?DNA is a molecule that tells cells in the body how and when to make proteins. – Proteins control how a living thing will look and function. – Genes are a part of DNA that tells cells in the body how to make proteins.  Genes give you your height, natural hair color, and eye color.Every day, processes inside the cell and events outside the cell (like radiation from the sun) damage DNA. DNA is important, so the cell uses systems made of proteins to find and repair the damage in the DNA. – If the cell cannot repair the damaged DNA, there is a risk the cell might grow into cancer.  In most cases, the cell dies to prevent this. In rare cases, the cell might not die and a tumor may develop.Some men with prostate cancer have faulty DNA repair genes in their tumors. Faulty DNA repair genes make faulty DNA repair proteins. – Sometimes faulty DNA repair genes cause cancer because the cell cannot repair DNA  very well.  – Faulty DNA repair genes can also make the tumor sensitive to some cancer treatments, including talazoparib.Talazoparib is a PARP inhibitor. A PARP inhibitor stops PARP proteins from working.If talazoparib stops PARP proteins from working and the DNA repair proteins are faulty at the same time, the tumor cells cannot grow. This means the tumor cells are more likely to die than cells with normal DNA repair proteins.What is talazoparib?PARP proteins are important for finding damaged DNA. PARP stands for poly(ADP-ribose) polymerase.2981Plain Language Summary of Publication Agarwal, Azad, Shore and co-authorsfuture science groupWhat is enzalutamide?Enzalutamide is approved to treat men with prostate cancer.Enzalutamide works by stopping androgens (like testosterone) from helping prostate cancer cells to grow.Enzalutamide may make the tumor cells behave like they have faulty DNA repair systems, even if the cells do not have faulty DNA repair genes.Why are researchers studying the combination of talazoparib and enzalutamide?  TALAPRO-2 will find out if combining talazoparib with enzalutamide will increase the length of time the men in the study live without their cancer getting worse when compared with men receiving enzalutamide and placebo.   Earlier studies suggest that talazoparib and enzalutamide may work  well together:  –  Enzalutamide may make the cancer cells more sensitive to talazoparib. –  Androgens (like testosterone) also need PARP proteins to help cancer cells grow. Therefore, talazoparib may make cancer cells more sensitive to enzalutamide.Future Oncol. (2022) 18(27)2982TALAPRO-2 study on metastatic castration-resistant prostate cancer Plain Language Summary of Publication future science group www.futuremedicine.comWho is taking part in the TALAPRO-2 study?Do not have significant problems with their heart, veins or arteries, kidney, liver, blood, or brain; or tumor-related issues with their spinal cord; or other previous cancersProgressive disease means the cancer is growing, spreading, or getting worse Prostate cancer is considered progressive if the man’s prostate-specific antigen  (also known as PSA) values increase, or if scans show growth or spread of the cancer in the bones or other tissues in the body PSA is a protein made by the prostate gland and found in the blood.  In men who have prostate cancer, levels of PSA are often higher than in men  who do not have prostate cancerThe TALAPRO-2 study is a Phase 3 study.   A Phase 3 study takes place after the early testing stages to find out if a treatment works in a larger number of patients with a particular disease. Enrollment for the TALAPRO-2 study took place in two parts. It began in December 2017 and is now complete after enrolling 1037 adult men (19 men in part 1 and 1018 men in part 2). All men have mCRPC with mild (or no) symptoms and have the following characteristics:1037 men with mCRPCAble to walk and carry out  light workCurrently taking drugs to lower testosterone levels in the blood or have undergone surgical castrationProgressive diseaseHave not taken any previous cancer treatments for their mCRPC that could reach their whole body (known as systemic treatments) or had recent radiation treatment or  recent surgery2983Plain Language Summary of Publication Agarwal, Azad, Shore and co-authorsfuture science group• Part 1 of the TALAPRO-2 study is complete and involved 19 men.• The aim of part 1 was to find out which dose of talazoparib should be used safely in combination with enzalutamide in part 2 of the study. • Part 2 enrollment is complete (no additional men will be enrolled). The goal was to enroll  1018 men.  – Men with and without errors in DNA repair genes are included in the study.All of the men in part 2 of the study are taking enzalutamide: Part 1 of the TALAPRO-2 studyPart 2 of the TALAPRO-2 studyA placebo does not contain any active ingredients (it is also known as a sugar pill).  The placebo and study drugs look alike. Sometimes, people feel their disease has improved just because they are taking a pill, even if it is only a placebo. This study is using a placebo pill to make sure that any changes to the men’s cancer are due to talazoparib in combination with enzalutamide, and not just because the men are taking an extra pill.Neither the men in the study nor the health professionals looking after them  will know whether the men are taking talazoparib or placebo.Based on the results of  part 1, researchers found  the appropriate starting  dose of talazoparib to be  0.5 mg per day Half of the men were randomly assigned to also receive talazoparibThe dose of enzalutamide is 160 mg per dayThe other half of the men are taking a placebo instead of talazoparibFuture Oncol. (2022) 18(27)2984TALAPRO-2 study on metastatic castration-resistant prostate cancer Plain Language Summary of Publication future science group www.futuremedicine.comWhat are the aims of the TALAPRO-2 study?How long men live without their cancer getting worsetalazoparib + enzalutamidemonths monthsenzalutamide + placebo• Part 2 of the TALAPRO-2 study will find out if combining talazoparib with enzalutamide, as a man’s first treatment for mCRPC, will increase the length of time the men in the study live without their cancer getting worse compared with enzalutamide plus placebo.  – Researchers will investigate these treatments in men with and without errors in selected DNA repair genes.• The men will have diagnostic imaging (CT, MRI, and bone scan) every 8 to 12 weeks to measure changes in the size  or number of sites with cancer outside of the prostate. – The scan results will tell researchers if the cancer is shrinking, growing, or staying the same.• Researchers will also look at other outcomes such as how long the men in the study live overall and any side effects they may have. – A side effect is a reaction (expected or unexpected) to a medicine or treatment you take.A CT scan uses a computer linked to an x-ray machine to make detailed pictures of areas inside  the body. The pictures are taken from different angles and are used to create  images of tissues and organs An MRI uses radio waves and a powerful magnet linked to a computer to make detailed pictures of areas inside the body. These pictures can show the difference between  normal tissue and tissue that may be cancer2985Plain Language Summary of Publication Agarwal, Azad, Shore and co-authorsfuture science groupWhere is the study taking place?TALAPRO-2 is currently studying men in 26 countriesArgentinaAustraliaBelgiumBrazilCanadaChileChinaCzech RepublicFinlandFranceGermanyHungaryIsraelItalyJapanNew ZealandNorwayPeruPolandPortugalRepublic of KoreaSouth AfricaSpainSwedenUnited KingdomUnited StatesWhere can I find more information?Original articleThe full title of the original article is 'Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design'. You can read the article for free at:  https://www.futuremedicine.com/doi/full/10.2217/fon-2021-0811The full citation of the original article is: Agarwal N, Azad A, Shore ND et al.: Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design.  Future Oncol. 18(4) doi.org/10.2217/fon-2021-0811Trial registration siteYou can read more about the Phase 3 TALAPRO-2 study at the following trial registration website:  Clinicaltrials.gov - trial number NCT03395197For more information on clinical studies in general, please visit:https://www.clinicaltrials.gov/ct2/about-studies/learnhttp://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-clinical-trials-areEducational resourcesYou can read more about prostate cancer on the American Society of Clinical Oncology Cancer.Net website at:  https://www.cancer.net/cancer-types/prostate-cancerPatient-focused information on prostate cancer from the NIH is available at: https://www.cancer.gov/types/prostateFinancial & competing interests disclosureFull author disclosure information can be found in the original article.Writing support for this summary was provided by Emily Messina of CMC AFFINITY, a division of IPG Health Health Medical Communications, and was funded by Pfizer.Who is sponsoring this study?The TALAPRO-2 trial is sponsored by Pfizer Inc. Astellas Pharma Inc. is providing enzalutamide. Pfizer and the authors would like to thank all of the men who participated or are participating in this study and their families, as well as the treating physicians, research nurses, study coordinators, and operations staff.Technical abbreviations CT stands for computed tomography. DNA stands for deoxyribonucleic acid. mCRPC stands for metastatic castration-resistant prostate cancer. MRI stands for magnetic resonance imaging. PARP stands for poly(ADP-ribose) polymerase. PSA stands for prostate-specific antigen.Future Oncol. (2022) 18(27)2986

Plain language summary of the design of the TALAPRO-2 study comparing talazoparib and enzalutamide versus enzalutamide and placebo in men with metastatic castration-resistant prostate cancer

https://scientiasalut.gencat.cat/bitstream/11351/8661/1/plain_language_summary_design_talapro_2_study_comparing_talazoparib_enzalutamide_versus_enzalutamide_placebo_men_metastatic_castration_resistant_prostate_cancer_2022.pdf

Plain language summary of the design of the TALAPRO-2 study comparing talazoparib and enzalutamide versus enzalutamide and placebo in men with metastatic castration-resistant prostate cancer

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