Guadecitabine and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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|ClinicalTrials.gov Identifier: NCT02901899|
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : August 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma||Drug: Guadecitabine Other: Laboratory Biomarker Analysis Biological: Pembrolizumab||Phase 2|
I. Measure objective response rate (RR) to guadecitabine and pembrolizumab in subjects with recurrent platinum resistant ovarian cancer (OC).
I. Measure progression free survival (PFS) for the combination of guadecitabine and pembrolizumab.
II. Progression free survival (PFS). III. Measure clinical benefit rate (CBR) for the combination of guadecitabine and pembrolizumab.
IV. Measure toxicity profiles to the combination of guadecitabine and pembrolizumab.
I. NY-ESO-1 and MAGE antigens' promoter methylation (pyrosequencing) and messenger ribonucleic acid (mRNA) expression levels (quantitative reverse transcriptase-polymerase chain reaction [RT-PCR]) will be measured before and after treatment in deoxyribonucleic acid (DNA) (plasma and/or tumor biopsies) and ribonucleic acid (RNA) (tumor biopsies), respectively.
II. Cytokine response (IFN gamma IL2, IL6, IL10, TNF alpha) will be measured in plasma by enzyme-linked immunosorbent assay (ELISA).
III. Measure LINE 1 methylation in DNA extracted from peripheral blood mononuclear cells (PBMCs) (measured on days 1 and 5 of cycles 1 and 2).
IV. Expression of the PD-L1 ligand will be measured by immunohistochemistry (IHC) in archival tumors.
V. Tumor infiltrating lymphocytes (TILs) will be quantified in tumor biopsies before and after treatment (IHC).
Patients receive guadecitabine subcutaneously (SC) on days 1-4 and pembrolizumab intravenously (IV) over 30 minutes on day 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 6 weeks for 1 year, and then every 9 weeks and, once a subject experiences confirmed disease progression or starts a new anticancer therapy, every 3 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label Phase II Trial of Guadecitabine and Pembrolizumab in Platinum Resistant Recurrent Ovarian Cancer|
|Actual Study Start Date :||November 2016|
|Estimated Primary Completion Date :||August 2019|
|Estimated Study Completion Date :||March 2020|
Experimental: Treatment (guadecitabine, pembrolizumab)
Patients receive guadecitabine SC on days 1-4 and pembrolizumab IV over 30 minutes on day 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Objective Response Rate (ORR) [ Time Frame: Up to 3 years ]Imaging scans will be assessed using the Immune Related Response Criteria (irRC) to measure ORR to guadecitabine and pembrolizumab in patients with recurrent platinum resistant Ovarian Cancer.
- Objective Response Rate (ORR) [ Time Frame: Up to 3 years ]Imaging scans will be assessed using The Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to evaluate ORR to guadecitabine and pembrolizumab in patients with recurrent platinum resistant Ovarian Cancer.
- Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]Measure PFS for the combination of guadecitabine and pembrolizumab as evaluated by RECIST v 1.1 assessed from first dose of study treatment until disease progression or death from any cause, assessed for up to 3 years.
- Clinical Benefit Rate (CBR) [ Time Frame: Up to 3 years ]CBR for the combination of guadecitabine and pembrolizumab will be defined according to response assessment criteria that evaluates imaging scans.
- Incidence of Adverse Events [ Time Frame: Up to 3 years ]Assess the toxicity of guadecitabine and pembrolizumab by measuring the number, type, grade, severity, and frequency of adverse events according to the National Cancer Institute Common Terminology Criteria Adverse events (CTCAE) v 4.03.
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): NCT02901899
|Contact: Study Coordinator||(312)email@example.com|
|Contact: Daniela Matei, MD||(312)472-4684|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Daniela E. Matei 312-472-4684 firstname.lastname@example.org|
|Principal Investigator: Daniela E. Matei, MD|
|Sub-Investigator: Emma Barber, MD|
|Sub-Investigator: Shohreh Shahabi, MD|
|Sub-Investigator: Wilberto Nieves-Neira, MD|
|Sub-Investigator: John Lurian, MD|
|The University of Chicago Medicine||Recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Gini Fleming, MD 773-702-6712|
|Principal Investigator: Gini Fleming, MD|
|Northwestern Lake Forest Hospital||Recruiting|
|Lake Forest, Illinois, United States, 60045|
|Contact: Valerine Nelson, MD 312-695-6180|
|Contact: Alok Pant, MD (847)582-2134|
|Sub-Investigator: Valerine Nelson, MD|
|Sub-Investigator: Alok Pant, MD|
|Principal Investigator:||Daniela Matei, MD||Northwestern University|