Combination ATR inhibitor and PARP Inhibitor in Recurrent Ovarian Cancer (CAPRI)

About the Study

This study will look at how well patients with recurrent ovarian, primary peritoneal or fallopian tube cancer respond to treatment with a targeted therapy known as an ATR inhibitor when combined with the PARP inhibitor Olaparib.

Type of Study

This is an open-label, non-randomized, phase 2 study.

• All participants will receive the same study drugs in different combinations
• All participants will know which medication they are receiving.
• The study will have four different groups of participants. Participants will be assigned to a group based on tumor testing, genetic testing, platinum sensitivity and number of prior treatments.

What the Study Entails:

• All patients will receive the PARP inhibitor olaparib (Lynparza) and the ATR inhibitor AZD6738
• The doses of each drug will depend on the participant's assigned study group (see below)
• Study participants will be followed for 2 years.

Study Group A

Participants assigned to this group have recurrent high grade serous ovarian, primary peritoneal or fallopian tube cancer for which standard curative treatments are no longer effective. These participants will receive: 

• 300 mg olaparib orally twice daily for 28 days.
• 160mg AZD6738 will be administered orally once daily on days 1 to 7.

Study Group B

Participants assigned to this group have recurrent high grade serous ovarian, primary peritoneal or fallopian tube cancer for which standard curative treatments are no longer effective. Participants must have 3 or fewer courses of chemotherapy since developing platinum-resistance. These participants will receive:

• 300 mg olaparib orally twice daily for 28 days.
• 160mg AZD6738 will be administered orally once daily on days 1 to 7.

For Study Group C

Participants assigned to this group have recurrent high grade serous ovarian, primary peritoneal or fallopian tube cancer for which standard curative treatments are no longer effective. Participants in this group must have received prior treatment with a PARP inhibitor, must have platinum sensitive disease, and must have either an inherited BRCA mutation or tumor mutation in BRCA1, BRCA2 or another "HRD gene" (for example PALB2) or biomarker testing that show that their tumor is HRD-positive. These participants will receive:

• 300 mg olaparib orally twice daily for 28 days.
• 160mg AZD6738 will be administered orally once daily on days 1 to 7.

For Study Group D1

Participants in this group may have any type of non-mucinous epithelial ovarian cancer (including clear cell or endometrioid types). Participants may be either platinum-sensitive or platinum-resistant. These participants will receive: 

• Patients will take a lower dose of olaparib (100-200 mg daily on a 28-day cycle).
• A higher dose of AZD6738 (160-320 mg daily for about 14 days) will be administered.

For Study Group D2

Participants assigned to this group have recurrent high grade serous ovarian, primary peritoneal or fallopian tube cancer for which standard curative treatments are no longer effective. Participants in this group must have received prior treatment with a PARP inhibitor, must have platinum sensitive disease, and must have either an inherited BRCA mutation or tumor mutation in BRCA1, BRCA2 or another "HRD gene" (for example PALB2) or biomarker testing that show that their tumor is HRD-positive. These participants will receive:

• Patients will take a lower dose of olaparib (100-200 mg daily on a 28-day cycle).
• A higher dose of AZD6738 (160-320 mg daily for about 14 days) will be administered.

Study Sites:

Maryland
Baltimore, MD
Johns Hopkins University School of Medicine
Contact Mary Kate Jones by email at: [email protected]  

Massachusetts
Boston, MA
Dana-Farber Cancer Institute                              
Contact: Kim MacNeill by email at: [email protected]  

Pennsylvania
Philadelphia, PA
Hospital of the University of Pennsylvania         
Contact: Diego Rodriguez by phone: 215-614-0234  or by [email protected]  
Contact: Fiona Simpkins, MD by phone 215-662-7336 or by email:  [email protected]   

People who belong to any of these groups may participate:

• Group A: recurrent high grade serous ovarian cancer for which standard curative treatments are no longer effective. 
• Group B: recurrent high grade serous ovarian cancer for which standard curative treatments are no longer effective. Participants must have received 3 or fewer courses of chemotherapy since developing platinum-resistance. 
• Group C: recurrent high grade serous ovarian cancer for which standard curative treatments are no longer effective. Participants in this group must have received prior treatment with a PARP inhibitor, must have platinum sensitive disease, and must have an inherited or tumor BRCA mutation or tumor mutation or a tumor mutation in or another "HRD gene" (for example PALB2) or biomarker testing that show that their tumor is HRD-positive.
• Group D1: any type of non-mucinous epithelial ovarian cancer (including clear cell or endometrioid types). Participants may be either platinum-sensitive or platinum-resistant. 
• Group D2: recurrent high grade serous ovarian cancer for which standard curative treatments are no longer effective. Participants in this group must have received prior treatment with a PARP inhibitor, must have platinum sensitive disease, and must have either an inherited BRCA mutation or tumor mutation in BRCA1, BRCA2 or another "HRD gene" (for example PALB2) or biomarker testing that show that their tumor is HRD-positive. 

• Have brain metastases diagnosed within the last year
• Have had prior treatment with AZD6738 or other cell cycle checkpoint inhibitors such as other ATM or ATR inhibitor, WEE-1 inhibitor, or CHK1 (or 1/2) inhibitor, 
• Have a serious cardiac condition
• Have had another active invasive malignancy within the last five years (Contact the study team for a list of exceptions.)
• Are immunocompromised or HIV-positive on highly active antiretroviral therapy (HAART)
• Patients whose disease progressed during first line platinum therapy are excluded for Study Groups A, B, C, D2.