A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02498613
Recruitment Status : Active, not recruiting
First Posted : July 15, 2015
Last Update Posted : November 8, 2023
|Condition or disease
|Advanced Malignant Solid Neoplasm Metastatic Lung Non-Small Cell Carcinoma Metastatic Lung Small Cell Carcinoma Metastatic Pancreatic Adenocarcinoma Metastatic Triple-Negative Breast Carcinoma Pancreatic Ductal Adenocarcinoma Stage III Breast Cancer AJCC v7 Stage III Lung Non-Small Cell Cancer AJCC v7 Stage III Lung Small Cell Carcinoma AJCC v7 Stage III Pancreatic Cancer AJCC v6 and v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIA Lung Non-Small Cell Cancer AJCC v7 Stage IIIA Lung Small Cell Carcinoma AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIB Lung Non-Small Cell Cancer AJCC v7 Stage IIIB Lung Small Cell Carcinoma AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7 Stage IV Lung Non-Small Cell Cancer AJCC v7 Stage IV Lung Small Cell Carcinoma AJCC v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Triple-Negative Breast Carcinoma Unresectable Lung Small Cell Carcinoma Unresectable Pancreatic Adenocarcinoma Unresectable Pancreatic Carcinoma Unresectable Triple-Negative Breast Carcinoma
|Other: 18F-Fluoromisonidazole Drug: Cediranib Maleate Other: Laboratory Biomarker Analysis Drug: Olaparib Procedure: Positron Emission Tomography
I. To determine the objective response rate (ORR) of cediranib (cediranib maleate) plus olaparib in combination in patients with advanced or metastatic solid tumors of the following tumor types: non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC).
I. To assess the safety and tolerability of oral administration of cediranib in combination with olaparib in patients with select advanced solid tumors.
II. To estimate progression free survival (PFS) in each tumor cohort.
I. To estimate the prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in tumors using the BROCA panel and to correlate tumor regression with mutations status. (Integrated) II. To evaluate changes in tumor hypoxia on cediranib treatment compared to baseline by [F-18] fluoromisonidazole (FMISO) positron emission tomography/computed tomography (PET/CT) in patients with NSCLC.
III. To evaluate levels of angiogenesis/inflammatory markers including VEGF at baseline and on treatment.
IV. To evaluate levels of circulating tumor deoxyribonucleic acid (ctDNA) at baseline and on treatment.
Patients receive cediranib maleate orally (PO) once daily (QD) on day 1. Patients undergoing FMISO scan also receive olaparib PO twice daily (BID) beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks and then every 4 weeks thereafter.
|Study Type :
|Interventional (Clinical Trial)
|Estimated Enrollment :
|Single Group Assignment
|None (Open Label)
|A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors
|Actual Study Start Date :
|August 31, 2016
|Estimated Primary Completion Date :
|December 31, 2023
|Estimated Study Completion Date :
|December 31, 2023
Experimental: Treatment (cediranib maleate, olaparib)
Patients receive cediranib maleate PO QD on day 1. Patients undergoing FMISO scan also receive olaparib PO BID beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity.
Drug: Cediranib Maleate
Other: Laboratory Biomarker Analysis
Procedure: Positron Emission Tomography
- Objective response rate [ Time Frame: Up to 4 weeks after completion of study treatment ]Measured by Response Evaluation Criteria in Solid Tumors version 1.1. The exact two-sided 95% confidence interval for the objective response rate will be reported.
- Incidence of adverse events [ Time Frame: Up to 4 weeks after completion of study treatment ]Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percentages and frequencies for categorical parameters, will be presented. Adverse medical events will be tabulated. National Cancer Institute toxicity grade 3 and grade 4 laboratory abnormalities will be listed.
- Progression-free survival [ Time Frame: The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 4 weeks after completion of study treatment ]Estimated using the Kaplan-Meier method with the 95% confidence intervals. Thomas and Grunkemeier confidence interval will be reported. The possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.
- Prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in each tumor cohort [ Time Frame: Up to 2 years ]In the first 20 endpoint-evaluable patients with non-small cell lung cancer and 20 endpoint-evaluable patients with triple negative breast cancer, the exploratory analyses will be done using Fisher's exact tests, Mann-Whitney U tests or McNemar's test depending on the type of data observed.
- Changes in tumor hypoxia by imaging [ Time Frame: Baseline to post-cediranib monotherapy ]Measured by 18F-fluoromisonidazole positron emission tomography/computed tomography scans (non-small cell lung cancer). For the pre- and post-cediranib therapy outcome analysis, paired t- test or Wilcoxon signed-rank test will be applied for the continuous variables.
- Changes in level of circulating tumor deoxyribonucleic acid (ctDNA) (all cohorts) [ Time Frame: Baseline to post therapy ]Will be assessed using paired t- test or Wilcoxon signed-rank.
- Changes in levels of angiogenesis/ inflammatory markers (angiome panel) (all cohorts) [ Time Frame: Baseline to post-therapy ]Will be assessed using paired t- test or Wilcoxon signed-rank.
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): NCT02498613
|United States, California
|UC San Diego Moores Cancer Center
|La Jolla, California, United States, 92093
|University of California Davis Comprehensive Cancer Center
|Sacramento, California, United States, 95817
|UC San Diego Medical Center - Hillcrest
|San Diego, California, United States, 92103
|UCSF Medical Center-Mount Zion
|San Francisco, California, United States, 94115
|United States, Connecticut
|Smilow Cancer Center/Yale-New Haven Hospital
|New Haven, Connecticut, United States, 06510
|New Haven, Connecticut, United States, 06520
|United States, Florida
|Moffitt Cancer Center-International Plaza
|Tampa, Florida, United States, 33607
|Moffitt Cancer Center
|Tampa, Florida, United States, 33612
|United States, Massachusetts
|Dana-Farber Cancer Institute
|Boston, Massachusetts, United States, 02215
|United States, Michigan
|Wayne State University/Karmanos Cancer Institute
|Detroit, Michigan, United States, 48201
|Weisberg Cancer Treatment Center
|Farmington Hills, Michigan, United States, 48334
|United States, Tennessee
|Vanderbilt University/Ingram Cancer Center
|Nashville, Tennessee, United States, 37232
|United States, Texas
|M D Anderson Cancer Center
|Houston, Texas, United States, 77030
|United States, Virginia
|Virginia Commonwealth University/Massey Cancer Center
|Richmond, Virginia, United States, 23298
|Canada, British Columbia
|BCCA-Vancouver Cancer Centre
|Vancouver, British Columbia, Canada, V5Z 4E6
|University Health Network-Princess Margaret Hospital
|Toronto, Ontario, Canada, M5G 2M9
|Joseph W Kim
|Yale University Cancer Center LAO