Treating Metastatic Solid Tumors with an Inherited or Acquired Gene Mutation Using the PARP Inhibitor Talazoparib

About the Study

This study is looking whether the drug talazoparib (also known as Talzenna) is safe and effective for treating people with advanced solid cancers (including breast, gastric, ovarian, pancreatic, prostate or other solid tumors) in people with an inherited mutation (found through genetic testing) or an acquired mutation (found with biomarker testing) in ATM, ATR, BRCA1, BRCA2, BRIP1, BAP1, BARD1, CDK12, CHEK1, CHEK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L or other genes. Talazoparib is a type of targeted therapy known as a PARP inhibitor. 

This study is open to people who have previously been treated with a PARP inhibitor treatment and people who have not been previously treated with a PARP inhibitor. 

What the Study Involves

Participants will receive talazoparib orally once daily for 28 days. This cycle will be repeated every 28 days as long as there isn’t disease progression or unacceptable side effects. Participants will undergo biopsy at the start of the study and 4 hours after talazoparib dose on day 1 of cycle 2. Participants can elect to have another biopsy, either at the start of the next cycle or at the time of disease progression.

Study Locations

Florida

• Gainesville
  University of Florida Health Science Center - Gainesville
  Lead Researcher: Thomas George, MD
  Contact: [email protected] 

Maryland

• Bethesda
  National Cancer Institute Developmental Therapeutics Clinic
  Lead Researcher: A.P. Chen, MD
  Contact: [email protected] 

Oklahoma

• Oklahoma City
  University of Oklahoma Health Sciences Center
  Lead Researcher: Abdul Rafeh Naqash, MD 
  Contact:  [email protected] 

Adults with the following may be eligible:

• Solid tumors (tumor site must be able to be biopsied) and documented inherited or tumor mutations in genes involved in DNA repair, such as:
  • BRCA1 or BRCA2, ATM, ATR, BRIP1, BAP1, BARD1, CDK12, CHEK1, CHEK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L, ARID1A, OR
  •  FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN
• Recurrent, locally advanced, or metastatic disease; disease has progressed after at least one standard therapy OR no acceptable standard treatment option exists
• Able to swallow oral medications (tablets or capsules). 
• Life expectancy > 3 months
• Patients with ovarian cancer:
  • Should have one prior platinum-based therapy
• Patients with pancreatic cancer:
  • Should have received prior platinum-containing therapy
• Patients with breast cancer:
  • Patients with HER2+ breast cancer should have had 2 prior therapies for metastatic cancer, including anti-HER2 therapy
  • Patients who are eligible for a PARP inhibitor must have had prior PARP inhibitor treatment (except talazoparib - patients who have previously received talazoparib are ineligible for the study)
• Patients with gastric cancer:
  • Patients with HER2+ gastric cancer should have had received anti-HER2 therapy for metastatic cancer
• Patients with prostate cancer:
  • Patients who are eligible for a PARP inhibitor must have had prior PARP inhibitor treatment (except talazoparib - patients who have previously received talazoparib are ineligible for the study)

People with the following may not be eligible: 

• people must wait 4 weeks after chemotherapy or radiation to start the study or 6 weeks for nitrosoureas or mitomycin C.
  • Must be at least 2 weeks since any prior administration of a study drug in another trial and be at least 1 week from palliative radiation therapy.
  • Patients who have had prior monoclonal antibody therapy must have completed that therapy at least 6 weeks prior to enrollment in the study.
• had prior treatment with talazoparib.
• receiving any other investigational agents.
• active brain metastases or carcinomatous meningitis.
• illnesses such as ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness.
• pregnant people and people who are currently lactating.
• people who require the use of anticoagulants such as warfarin.
• history of prior cancer within the past 3 years (other than certain types of skin cancers that have been controlled).
• HIV-infected patients on effective antiretroviral therapy with undetected viral load within 6 months are eligible.