Olaparib with Cediranib or Ceralasertib for People with Advanced or Metastatic Breast Cancer and with a BRCA1 or BRCA2 Mutation

About the Study

This study is for people with a BRCA1 or BRCA2 genetic mutation, with metastatic, HER2-negative breast cancer who were previously treated with a PARP inhibitor. The study will look at how well the drug Olaparib works when combined with either Cediranib or Ceralasertib in reducing the size of cancer and expanding the length of time patients respond well to the treatment.  

What the Study Involves

Participants are assigned to one of two groups in this study. They are followed for 30 days after completion of study treatment.

Group1

Participants will take Olaparib orally twice a day and Cediranib orally once a day on day 1 to day 28. They will continue with the cycles until the treatment stops working or causes serious side effects.

Group2

Participants will take Olaparib orally twice a day on day 1 to day 28 and Ceralasertib orally once a day on day 1 to day 7. They will continue with cycles until the treatment stops working or causes serious side effects.

Study Site

Texas

MD Anderson Cancer Center
Houston, Texas 77030

Assigned female at birth aged 18 years and older, who meet the following criteria:

All groups

• Have advanced or metastatic breast cancer that is HER2 negative with a BRCA1 or BRCA2 mutation. People with Estrogen receptor positive (ER+) breast cancer must have disease progression after previous endocrine therapy or these treatments are inappropriate.
• Have a life expectancy of more than 16 weeks
• Have a negative pregnancy test prior to study treatment and during study
• Use contraception 30 days prior to first treatment, for duration of the treatment, and at least 1 month after finishing the trial treatment
• Are willing to follow study schedule and instructions
• Have measurable diseases that can be detected with a CT or MRI scan
• Are willing to have a biopsy of the metastatic lesion before starting trial treatment
• Are willing to provide blood samples before starting treatment and at the end of the study
• Have been treated with any PARP inhibitor for at least 4 months
• Are able to swallow oral medication
• Do not have gastrointestinal illnesses that interfere with the absorption of medications
• Have adequate kidney and thyroid function

Group1

• Have adequate blood pressure (systolic blood pressure [SBP] =< 140 mmHg; diastolic blood pressure [DBP] =< 90 mmHg) that is checked within 2 weeks prior to the trial study and on maximum of 3 antihypertensive medications.

People under 18 years old and who:

• Had surgery, chemotherapy or radiation therapy within 3 weeks prior to start the study treatment
• Have had previous treatment with Ceralasertib and Cediranib
• Had severe side effects from previous treatment
• Have not recovered from side effects of treatments that they received more than 3 weeks
• Receive any other investigational treatment within the past 4 weeks
• Have untreated brain metastases, symptoms of brain metastases, or spinal cord compression
• Have received prior treatment with a drug known as a VEGF inhibitor
• Have history of allergic reactions to the ingredients of Olaparib or Cediranib or Ceralasertib
• Use complementary alternative medications including natural herbal products within 7 days prior to study treatment
• Have other invasive cancers within the past 5 years except skin cancer, breast cancer and cervix cancer on early stages
• Have other uncontrolled illness including heart disease, lung disease, active infection or a severe mental illness that would limit the ability to participate in the study
• Undergone surgery, open biopsy, or injury within 28 days prior to starting Cediranib
• Have bowel obstruction, something blocks your intestines and causes pain and discomfort, within 3 months before the study treatment
• Have significant bleeding within the last 1 month prior to study enrollment
• Have an infection in the stomach, within the 3 months prior to study enrollment
• Need intravenous (IV) fluids or total parenteral nutrition
• Have myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) 
• Have infections including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
• Have uncontrolled seizures
• Are pregnant or are breast feeding
• Have prior bone marrow transplant
• Have progression disease within 1 months after finishing platinum-based chemotherapy
• (Group1) Have a bleeding disease
• (Group2) diagnosis with ataxia telangiectasia (Louis-Bar syndrome)