Guadecitabine and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title: An Open Label Phase II Trial of Guadecitabine and Pembrolizumab in Platinum Resistant Recurrent Ovarian Cancer

Status Completed

Clinical Trial Summary

The purpose of this study is to look at how patients respond to treatment with guadecitabine and pembrolizumab. The researchers will also be looking at the amount of time it takes for cancer to get worse when participants take the study drugs. All participants will be treated with guadecitabine and pembrolizumab. Guadecitabine interferes with the cancer cells' DNA and can increase the production of certain proteins, making cancer cells more recognizable by the immune system. Pembrolizumab helps your immune system to kill cancer cells. Thus the combination of guadecitabine and pembrolizumab may increase the ability of the immune system to eliminate cancer cells. Researchers want to find out whether the combination of guadecitabine and pembrolizumab is effective in treating ovarian cancer that has not responded to traditional chemotherapy. Participants will keep receiving treatment until their cancer gets worse, they have side effects, or they decide they don't want to receive the treatment anymore. After stopping treatment, the study doctor will watch participants for side effects and follow their condition every 6-12 weeks. The study aims to keep track of participants' medical conditions for the rest of their lives. This helps us look at the long-term effects of the study drugs.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Measure objective response rate (RR) to guadecitabine and pembrolizumab in subjects with recurrent platinum resistant ovarian cancer (OC).

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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).

OUTLINE:

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. ;

Related Conditions & MeSH terms

• Carcinoma
• Recurrence
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

• NCT number: NCT02901899
• Study type: Interventional
• Source: Northwestern University
• Status: Completed
• Phase: Phase 2
• Start date: November 11, 2016
• Completion date: March 31, 2023