Olaparib and Durvalumab to Treat Patients With Metastatic Triple Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03801369|
Recruitment Status : Recruiting
First Posted : January 11, 2019
Last Update Posted : January 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Triple Negative Breast Cancer Breast Cancer ER-Negative PR-Negative HER2-Negative Breast Cancer ER-Negative PR-Negative HER2-Negative Breast Neoplasms Triple-Negative Breast Cancer Triple Negative Breast Cancer Triple-Negative Breast Neoplasm||Drug: Olaparib Biological: Durvalumib||Phase 2|
I. Assess overall response to treatment
I. Assess participant benefit from treatment
II. Determine the time to disease progression following response to study therapy
III. Determine time to first disease progression or death of participants enrolled on the study
IV. Determine survival of participants enrolled on the study
V. Assess safety and tolerability of the proposed therapy
I. Examine response rates depending on tumor characteristics
II. Identify predictive biomarkers of sensitivity to therapy
III. Identify emerging mechanism of resistance to therapy
IV. Determine changes in tumor cells induced by PARP inhibitors
OUTLINE: This is an open-label, single-arm phase II study of olaparib and durvalumab.
Participants with biopsy proven TNBC will undergo a pre-treatment biopsy, after which they will receive a 4 week, single cycle, induction treatment of olaparib (oral, twice a day). At the 4 week mark, participants will then undergo a repeat on-treatment biopsy, following which durvalumab will be administered (IV over 1 hr) every 4 weeks, in addition to olaparib. Treatment courses repeat every 28 days for 12 cycles.
At the completion of all on-study procedures, participants will be considered off-treatment and will be followed every 6 months for disease and survival outcomes up to 1 year. Participants will be asked to submit an optional tumor biopsy in the event of disease progression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Open Label, Study of Olaparib and Durvalumab (MEDI4736) in Patients With Metastatic Triple Negative Breast Cancer|
|Actual Study Start Date :||December 12, 2018|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Experimental: Treatment (Olaparib and Durvalumab)
Participants receive a 4 week, single cycle, induction treatment of olaparib (oral, twice a day). At the 4 week mark, participants will then undergo a repeat on-treatment biopsy, following which durvalumib will be administered (IV over 1 hr) every 4 weeks, in addition to olaparib. Treatment courses repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Given PO (Orally) 300 mg twice daily, for 4 weeks (induction) then every 28 days for up to 12 cycles
Given IV (infusion), 1500 mg over 1 hr starting at 4 weeks (following induction) and repeating every 4 weeks for up to 12 cycles.
Other Name: MEDI4736
- Objective Response Rate (ORR) [ Time Frame: Up to 6 months post treatment ]Using the efficacy analysis set, the estimate of ORR will be measured and reported with 95% exact confidence interval. Participants who achieve a complete response (CR) or a partial response (Pr) on the current protocol will be qualified as achieving a response, and will count towards the ORR measurement.
- Incidence of grade 3+ acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 [ Time Frame: Up to 3 months post treatment ]Incidence will be determined for participants with TNBC that received at least one dose of olaparib and/or durvalumab. The 95% confidence interval will be reported with the point estimate of toxicity rate
- Clinical benefit rate (CBR) for olaparib in combination with durvalumab [ Time Frame: Up to 6 months post treatment ]An estimate of CBR will be measured and reported with 95% exact confidence interval. Participants who achieve a CR, Pr, or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy, and will count towards the CBR measurement.
- Progression-free survival (PFS) for olaparib in combination with durvalumab [ Time Frame: Up to 1 year post treatment ]PFS is defined as the time from first treatment with olaparib (i.e., cycle 1 day 1) to the first of either recurrence or relapse (anywhere in the body), or death at time of last follow-up at 12-months. The estimated distribution of the PFS will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available
- Overall survival (OS) olaparib in combination with durvalumab [ Time Frame: Up to 1 year post treatment ]OS is defined as the time from first treatment with olaparib (i.e., Day 1) to the date of death or last follow-up at 12 months. The estimated distribution of the OS will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.
- Duration of response (DOR) for olaparib in combination with durvalumab [ Time Frame: Up to 6 months post treatment ]The duration of overall response is measured from the time measurement criteria are met for CR or Pr (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. If a participant dies, irrespective of cause, without documentation of recurrent or progressive disease beforehand, then the date of death will be used to denote the response end date.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03801369
|United States, Oregon|
|OHSU Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Zahi Mitri, MD 503-494-9160 email@example.com|
|Principal Investigator: Zahi Mitri, MD|
|Principal Investigator:||Zahi Mitri, MD||OHSU Knight Cancer Institute|