Talazoparib for Advanced Cancer
Recruiting in Palo Alto (17 mi)
+3 other locations
Overseen ByA P Chen
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must be taking: GnRH agonists
Must not be taking: Investigational agents
Disqualifiers: Active brain metastases, Uncontrolled illness, others
No Placebo Group
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial studies if talazoparib works in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and has mutation(s) in deoxyribonucleic acid (DNA) damage response genes who have or have not already been treated with another PARP inhibitor. Talazoparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. All patients who take part on this study must have a gene aberration that changes how their tumors are able to repair DNA. This trial may help scientists learn whether some patients might benefit from taking different PARP inhibitors "one after the other" and learn how talazoparib works in treating patients with advanced cancer who have aberration in DNA repair genes.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking medications that might affect the activity of talazoparib, the principal investigator will review your case to determine eligibility. Patients on certain anticoagulants like warfarin are excluded, but low-dose warfarin is allowed.
Is Talazoparib safe for humans?
Talazoparib has been shown to have a manageable safety profile in patients with advanced breast cancer and metastatic prostate cancer, meaning that while it can cause side effects, they are generally considered controllable.
12345How is the drug Talazoparib unique for treating advanced cancer?
Talazoparib is unique because it is an oral drug that specifically targets and inhibits PARP enzymes, which are crucial for repairing damaged DNA in cancer cells. This mechanism, known as synthetic lethality, is particularly effective in patients with BRCA mutations, offering better outcomes compared to traditional chemotherapy.
12467Eligibility Criteria
Adults with advanced cancer and specific DNA repair gene mutations, who have progressed after standard therapy or lack treatment options. They must be able to swallow pills, have a life expectancy over 3 months, acceptable blood counts and organ function, and women must use contraception. Excluded are those with HIV, recent chemotherapy or radiotherapy, lactating women, pregnant women, prior talazoparib treatment.Inclusion Criteria
Your absolute neutrophil count is at least 1,500 per microliter.
I am using a reliable birth control method.
I can take care of myself but might not be able to do heavy physical work.
+16 more
Exclusion Criteria
You are taking any other experimental medications.
I have not had chemotherapy or radiotherapy recently.
I have received monoclonal antibody therapy recently.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive talazoparib orally once daily on days 1-28 of each cycle, with cycles repeating every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and blood sample collection, as well as CT scan or MRI throughout the study.
28 days per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days post-treatment.
30 days
Participant Groups
The trial is testing Talazoparib's effectiveness in patients with advanced cancers that have spread and contain DNA repair gene mutations. It involves taking the drug to see if it prevents cancer cells from repairing their DNA damage which may lead to cell death.
1Treatment groups
Experimental Treatment
Group I: Treatment (talazoparib)Experimental Treatment5 Interventions
Patients receive talazoparib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and blood sample collection as well as CT scan or MRI throughout the study.
Talazoparib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Talzenna for:
- Deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer
🇪🇺 Approved in European Union as Talzenna for:
- Monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Oklahoma Health Sciences CenterOklahoma City, OK
National Institutes of Health Clinical CenterBethesda, MD
National Cancer Institute Developmental Therapeutics ClinicBethesda, MD
University of Florida Health Science Center - GainesvilleGainesville, FL
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Talazoparib: First Global Approval. [2020]Talazoparib (TALZENNA™) is an oral inhibitor of the polyadenosine 5'-diphosphoribose polymerase (PARP) enzymes, which play a critical role in repairing DNA single-strand breaks. It has been developed by Pfizer and was recently approved in the USA for the treatment of adults with deleterious or suspected deleterious germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer (as detected by a US FDA-approved assay). A regulatory assessment for talazoparib in this patient population is underway in the EU, with talazoparib also undergoing development for use in metastatic castration-resistant prostate cancer and various solid tumours, and as neoadjuvant therapy in early triple negative breast cancer. This article summarizes the milestones in the development of talazoparib leading to its first approval for the treatment of adults with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative, locally advanced or metastatic breast cancer.
Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial. [2021]Talazoparib (1 mg/day) exhibited promising efficacy and safety in patients with advanced breast cancer during ABRAZO (NCT02034916); this study evaluated patient-reported outcomes (PROs).
A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). [2021]Label="PURPOSE">To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer.
Talazoparib to treat BRCA-positive breast cancer. [2019]Talazoparib tosylate (BMN-673, Talzenna; Pfizer) is an oral poly [ADP-ribose] polymerase (PARP) inhibitor (PARPi) that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of germline BRCA-mutated locally advanced or metastatic breast cancer (BC). In preclinical and clinical studies, talazoparib exerted superior efficacy and offered a significant clinical benefit in advanced or metastatic BC patients harboring germline BRCA mutations compared with other PARPi and standard chemotherapy regimens through the concept of synthetic lethality. Thus, this review provides insight into the results of preclinical and clinical studies, highlights the current challenges of talazoparib and suggests innovative approaches to further improve its clinical efficacy and expand the use of talazoparib in advanced BC and/or triple-negative BC treatments beyond BRCA mutations.
Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1. [2023]Talazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations.
Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. [2021]Label="PURPOSE">Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (gBRCA-positive) and operable breast cancer.
Talazoparib Bests Chemo for Breast Cancer. [2019]Patients with advanced or metastatic HER2-negative breast cancer and germline BRCA1/2 mutations may benefit from talazoparib, according to data from a phase III trial. Compared with chemotherapy, the investigational PARP inhibitor induced some complete responses, prolonged progression-free survival, and improved patients' overall quality of life.