Olaparib in Treating Patients With Metastatic or Advanced Urothelial Cancer With DNA-Repair Defects
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03375307|
Recruitment Status : Recruiting
First Posted : December 18, 2017
Last Update Posted : April 1, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Bladder Carcinoma Advanced Urothelial Carcinoma Metastatic Bladder Urothelial Carcinoma Metastatic Urothelial Carcinoma Stage III Bladder Cancer AJCC v8 Stage IIIA Bladder Cancer AJCC v8 Stage IIIB Bladder Cancer AJCC v8 Stage IV Bladder Cancer AJCC v8 Stage IVA Bladder Cancer AJCC v8 Stage IVB Bladder Cancer AJCC v8||Procedure: Biospecimen Collection Drug: Olaparib||Phase 2|
I. To evaluate the efficacy of olaparib in two cohorts of patients with metastatic/advanced urothelial carcinoma (UC) pre-selected by DNA-repair defects as measured by overall response rate (ORR).
I. To describe the effect of therapy on progression free survival (PFS). II. To describe the effect of therapy on overall survival (OS). III. To describe the safety/tolerability and drug-related toxicities of olaparib.
IV. To follow patients without the pre-selected DNA-repair defects for survival.
I. To determine the proportion of patients with DNA-repair pathway-mutated genes in metastatic UC (patient cohort referred for screening).
II. To correlate levels of baseline circulating tumor cells (CTCs) with survival in untreated patients.
III. To explore tumor-mutational profiles in metastatic tumor biopsies, saliva "normal" DNA, changes in tumor or peripheral immune characteristics, or tumor associated somatic mutation load in blood DNA in response to treatment.
IV. To explore changes in plasma cytokines and correlate with clinical response.
V. To correlate levels of circulating endothelial cells with clinical outcome. VI. To correlate levels of circulating tumor cells (CTCs) with clinical outcome.
VII. To correlate peripheral immune and DNA damage response transcriptional signatures with clinical outcomes.
VIII. To determine the effectiveness of using next-generation sequencing (NGS) to identify DNA-repair pathway gene defects in tumor samples and circulating DNA and identify patients with UC suitable for PARP inhibition.
IX. To determine the expression of Schlafen 11 (SLFN11) in tumor versus (vs.) stroma cells, and the potential tumor heterogeneity based on SLFN11 expression.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients that have cancer-associated DNA-repair gene mutations receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients that do not have cancer-associated DNA-repair gene mutations undergo blood sample collection at baseline.
After completion of study treatment, patients are followed up at 4 weeks, every 2 months for 1 year, then every 3 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Olaparib (AZD2281) in Patients With Metastatic/Advanced Urothelial Carcinoma With DNA-Repair Defects|
|Actual Study Start Date :||August 3, 2018|
|Estimated Primary Completion Date :||August 21, 2023|
|Estimated Study Completion Date :||August 21, 2023|
Experimental: Cohort I (olaparib)
Patients that have cancer-associated DNA-repair gene mutations receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Cohort II (biospecimen collection)
Patients that do not have cancer-associated DNA-repair gene mutations undergo blood sample collection at baseline.
Procedure: Biospecimen Collection
Undergo blood collection
- Overall response rate (ORR) [ Time Frame: Up to 5 years ]Will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). ORR will be reported along with 95% exact confidence intervals.
- Progression free survival (PFS) [ Time Frame: From the date of olaparib initiation to investigator-assessed clinical progression or radiographic progression (by RECIST), or death from any cause, whichever occurs first, assessed up to 5 years ]PFS will be determined using a Kaplan-Meier curve, with probabilities at various time points indicated along with appropriate confidence intervals.
- Incidence of adverse events [ Time Frame: Up to 5 years ]Will be assessed according to the Common Terminology Criteria for Adverse Events version 5.0.
- Individual deoxyribonucleic acid (DNA)-repair defects [ Time Frame: Up to 5 years ]The association between individual DNA-repair defects and ORR will be determined using Fisher's exact test.
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): NCT03375307
|United States, California|
|UC San Diego Moores Cancer Center||Recruiting|
|La Jolla, California, United States, 92093|
|Contact: Site Public Contact 858-822-5354 email@example.com|
|Principal Investigator: Rana R. McKay|
|Los Angeles County-USC Medical Center||Active, not recruiting|
|Los Angeles, California, United States, 90033|
|USC / Norris Comprehensive Cancer Center||Active, not recruiting|
|Los Angeles, California, United States, 90033|
|USC Norris Oncology/Hematology-Newport Beach||Active, not recruiting|
|Newport Beach, California, United States, 92663|
|UC Irvine Health/Chao Family Comprehensive Cancer Center||Recruiting|
|Orange, California, United States, 92868|
|Contact: Site Public Contact 877-827-8839 firstname.lastname@example.org|
|Principal Investigator: Arash Rezazadeh Kalebasty|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Site Public Contact 916-734-3089|
|Principal Investigator: Mamta Parikh|
|United States, Colorado|
|University of Colorado Hospital||Suspended|
|Aurora, Colorado, United States, 80045|
|United States, Kentucky|
|University of Kentucky/Markey Cancer Center||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: Site Public Contact 859-257-3379|
|Principal Investigator: Peng Wang|
|United States, Maryland|
|NCI - Center for Cancer Research||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Site Public Contact 800-411-1222|
|Principal Investigator: Andrea B. Apolo|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Contact: Site Public Contact 405-271-8777 email@example.com|
|Principal Investigator: Abhishek Tripathi|
|Principal Investigator:||Andrea B Apolo||National Cancer Institute LAO|