CISPLATIN + AZD-1775 In Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03012477|
Recruitment Status : Completed
First Posted : January 6, 2017
Results First Posted : November 23, 2021
Last Update Posted : November 23, 2021
This research study is studying a combination of drugs as a possible treatment for triple-negative breast cancer that has spread to other areas of the body. The names of the study interventions involved in this study are:
|Condition or disease||Intervention/treatment||Phase|
|Triple-negative Metastatic Breast Cancer||Drug: Cisplatin Drug: AZD1775||Phase 2|
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved AZD1775 as a treatment for any type of cancer. Cisplatin is FDA approved for other cancers and has been shown to be an active treatment for breast cancer.
AZD1775 is a drug that is designed to block a protein called Wee-1 which may control the ability of certain cancer cells to grow or divide. Cisplatin works by damaging the DNA inside the cancer cells which prevents them from dividing. By combining AZD1775 and Cisplatin, cancer cells may potentially be more effectively killed.
In this research study, the investigators are looking to determine whether the combination of AZD1775 and cisplatin is an effective treatment for triple negative breast cancer that has spread to other parts of the body.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Cisplatin + AZD1775 in Metastatic Triple-negative Breast Cancer and Evaluation of pCDC2 as a Biomarker of Target Response|
|Actual Study Start Date :||January 18, 2017|
|Actual Primary Completion Date :||May 7, 2019|
|Actual Study Completion Date :||November 30, 2020|
Experimental: cisplatin + AZD1775
Treatment will consist of one cycle of cisplatin monotherapy (cisplatin 75 mg/m2 IV x1) followed by combination therapy of AZD1775 plus cisplatin starting 21 days(1 cycle) later.
AZD1775 will be administered 200 mg as twice daily oral dosing predetermined dosing schedule, in combination with Cisplatin predetermined dosage every 21 days.
At least 10 patients will undergo a research biopsy within 5-48 hours after beginning cisplatin (Cycle 1 Day 1) and then again within 5-8 hours after the last dose of AZD1775 in cycle 2 (Cycle 2 Day 3).
Other Name: Platinol
Wee1 tyrosine kinase inhibitor
- Objective Response Rate [ Time Frame: Evaluated every 6 weeks from the time of their first treatment, per RECIST 1.1. Duration of therapy will depend on individual response, evidence of disease progression and tolerance, up to 1 year ]The objective response rate (ORR) was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
- Median Progression-free Survival (PFS) [ Time Frame: From date of initiation of study treatment until the date of first documented progression or date of death from any cause, whichever came first (approximately 3 years and 11 months ). ]Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
- Change in pCDC2 After Therapy With AZD1775 in Paired Biopsies [ Time Frame: Biopsies will occur 5-48 hours after the C1D1 cisplatin dose (ie. C1D2or C1D3) and 5-8hrs (+/- 24hrs) after the last dose of AZD1775 on C2D3 ]
- Number of p53 Mutations [ Time Frame: Biopsies will occur 5-48 hours after the C1D1 cisplatin dose (ie. C1D2or C1D3) and 5-8hrs (+/- 24hrs) after the last dose of AZD1775 on C2D3 ]
- Number of of BRCA1/2 Mutation [ Time Frame: Biopsies will occur 5-48 hours after the C1D1 cisplatin dose (ie. C1D2or C1D3) and 5-8hrs (+/- 24hrs) after the last dose of AZD1775 on C2D3 ]
- Number of Patients Have Changes in Markers for DNA Damage [ Time Frame: Biopsies will occur 5-48 hours after the C1D1 cisplatin dose (ie. C1D2or C1D3) and 5-8hrs (+/- 24hrs) after the last dose of AZD1775 on C2D3 ]Formalin-fixed, paraffin-embedded (FFPE) biopsy specimens will be subjected to immunohistochemical analyses using standard procedures.
- Correlation Between Next Generation Sequencing of Tumors and Participant Outcomes [ Time Frame: ORR evaluated every 6 weeks from the time of their first treatment; PFS evaluated rom date of initiation of study treatment; Biopsies will occur 5-48 hours after cycle 1 and 5-8hrs after cycle 2. Follow up approximately 3 years and 11 months. ]Correlation compute between ORR and PFS, based on all participants data.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03012477
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Sara Tolaney, MD, MPH||Dana-Farber Cancer Institute|