Testing the Sequential Combination of the Anti-cancer Drugs Olaparib Followed by Adavosertib (AZD1775) in Patients With Advanced Solid Tumors With Selected Mutations and PARP Resistance, STAR Study
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|ClinicalTrials.gov Identifier: NCT04197713|
Recruitment Status : Suspended (Other - FDA Clinical Hold)
First Posted : December 13, 2019
Last Update Posted : July 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Metastatic Malignant Solid Neoplasm Refractory Malignant Solid Neoplasm Unresectable Malignant Solid Neoplasm||Drug: Adavosertib Drug: Olaparib||Phase 1|
I. To determine the safety and tolerability of olaparib in sequential treatment with adavosertib (AZD1775).
II. To establish the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of this sequential schedule in patients with advanced solid tumors in a post-poly adenosine diphosphate (ADP) ribose polymerase inhibitor (PARPi) population.
III. To assess the safety and toxicity profile of the sequential treatment of olaparib and AZD1775 in a post-PARPi population.
I. To assess putative predictive biomarkers of response and resistance to the sequential treatment of olaparib and AZD1775 in a post-PARPi population.
II. To evaluate a novel experimental trial design involving sequential dosing of olaparib and AZD1775 in a post-PARPi population.
III. To observe and record anti-tumor activity.
OUTLINE: This is a dose-escalation study of adavosertib.
Patients receive olaparib orally (PO) twice daily (BID) on days 1-5 and 15-19 of each cycle and adavosertib PO once daily (QD) on days 8-12 and 22-26 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Sequential Trial of Agents Against DNA Repair (STAR)|
|Actual Study Start Date :||April 15, 2020|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||June 30, 2023|
Experimental: Treatment (olaparib, adavosertib)
Patients receive olaparib PO BID on days 1-5 and 15-19 of each cycle and adavosertib PO QD on days 8-12 and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Incidence and severity of dose-limiting toxicities [ Time Frame: Up to 28 days ]
- Incidence of adverse events [ Time Frame: Up to 30 after administration of last dose of study drug ]Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Anti-tumor activity [ Time Frame: Up to 2 years ]Will correlate antitumor activity of the sequentially-administered combination of olaparib and adavosertib (AZD1775) with the detection of putative predictive biomarkers of response and resistance.
- Maximum tolerated dose (MTD) [ Time Frame: Up to 2 years ]Will assess if an MTD can be safely established using sequentially administered combination olaparib and AZD1775.
- Overall response rate (ORR) ( complete response [CR] + partial response [PR]) [ Time Frame: Up to 2 years ]We will estimate ORR with 95% confidence intervals (CI). Inferences and estimation are based on the exact binomial test.
- Duration of response (DOR) [ Time Frame: 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, assessed up to 2 years ]Will use the Kaplan-Meier method to estimate DOR in these distributions.
- Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years ]Will use the Kaplan-Meier method to estimate PFS in these distributions.
- Overall survival (OS) [ Time Frame: From start of treatment to time of death, assessed up to 2 years ]Will use the Kaplan-Meier method to estimate OS in these distributions.
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): NCT04197713
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Timothy A Yap||University of Texas MD Anderson Cancer Center LAO|