Study of the PARP inhibitor AZD9574 Alone and Combined with Other Cancer Medicines to Treat People with Advanced Solid Cancers (CERTIS1 Study)

About the Study

This research involves studying a drug called AZD9574 on its own and in combination with other anti-cancer drugs in people with advanced cancer that has come back or progressed. AZD9574 is a type of targeted therapy known as a PARP inhibitor. The study aims to understand the safety, tolerance, how the drug moves in the body, how it affects the body, and its initial effectiveness.

What the Study Involves

People will be enrolled and assigned to study treatments. This study consists of individual groups each evaluating the safety and effectiveness of the drug AZD9574.

Study Groups:

Group 1

• Part A:
  • Participants with advanced or recurrent (cancer that has come back) ovarian, breast, pancreatic, or prostate cancer who are eligible for a PARP inhibitor will receive increasing doses of the drug AZD9574.
• Part B:
  • Participants with HER2-negative breast cancer who have a BRCA1, BRCA2, PALB2, RAD51C or RAD51d mutation who have not had treatment with a PARP inhibitor will receive the drug AZD9574.

Group 2

• Part A:
  • Participants with IDH 1/2-mutant glioma, commonly observed in lower-grade glioma and secondary glioblastomas, who have not had treatment with a PARP inhibitor will receive increasing doses of the drug AZD9574 in combination with Temozolomide (TMZ.)
     

Study Sites - United States

California

• Los Angeles
  UCLA 
• San Francisco
  UCSF

Illinois

• Chicago
  Robert H. Lurie Comprehensive Cancer Center

Massachusetts

• Boston
  Dana-Farber Cancer Institute

New York

• New York
  Memorial Sloan Kettering

Oregon

• Portland
  OHSU Knight Cancer Institute

Texas

• Houston
  MD Anderson Cancer Center

Study Sites - International

• Australia
• Korea
• Spain
• Sweden

People who:

• are 18 years of age and older.
• are not pregnant or plan to become pregnant during the study and agree to use two methods of contraception while in the study until 3 months after the study.
• have cancer that has recurred or progressed.
• are eligible to receive a PARP inhibitor
• have a visible lump or spot that hasn't been treated with radiation before and can be accurately measured at the beginning of the study.

Group 1 participants who:

• have received platinum chemotherapy for advanced breast cancer are eligible to enter the study provided there has been no evidence of disease progression during the platinum chemotherapy.
• have received prior platinum-based chemotherapy as neoadjuvant/adjuvant treatment (treatment prior to, or after surgery) are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and first dose when enrolled in the study.

Group 2 participants must also meet these criteria:

• must have IDH1/2-mutant glioma.
• should have progressive disease after prior radiation therapy and one prior line of alkylating chemotherapy for their disease.
• have a recurrent disease thar is evaluable by MRI.

People who:

• had major surgery within 4 weeks of the first dose of study medication.
• underwent wide radiation treatment within the last 4 weeks or received limited radiation for relief purposes within the last 2 weeks from the first dose of the study intervention.
• have a history of uncontrolled seizures or with need for administration of more than 2 antiepileptic drugs, or history of epileptic disorder or any seizure history unrelated to tumor.
• have a history of severe brain injury or stroke.
• have any evidence of severe or uncontrolled systemic diseases including active bleeding diathesis, active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).