Pembrolizumab With Axitinib in Recurrent Endometrial Cancer
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|ClinicalTrials.gov Identifier: NCT04197219|
Recruitment Status : Withdrawn (PI is leaving institution)
First Posted : December 13, 2019
Last Update Posted : November 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Endometrial Cancer||Drug: Pembrolizumab Drug: Axitinib||Phase 2|
This is a Phase 2, open label study of pembrolizumab in combination with axitinib in adult women with recurrent endometrial cancer with deficient mismatch repair system. Twenty-six participants in total will be enrolled into the study. All participants enrolled will receive pembrolizumab as standard of care combined with axitinib.
Axitinib is approved by the Food and Drug Administration (FDA) for treatment in certain participants with advanced renal cell cancer but is considered investigational (experimental) in this study. However, it is not FDA approved for recurrent endometrial cancer. Axitinib is a type of drug called a tyrosine kinase inhibitor. It is thought to work by blocking tumor vasculature and decreasing the blood supply to the tumor. Also it has been shown to improve the function of immune cells within the tumor which may enable them to kill the tumor.
Pembrolizumab is an immunotherapy that is FDA approved to treat participants with recurrent endometrial cancer with deficient mismatch repair system (dMMR). dMMR means having genetic changes within the tumor that make it unstable and potentially able to benefit from immunotherapy. Pembrolizumab works by improving the function of the immune cells enabling them to kill cancer cells.
Axitinib given in combination with pembrolizumab has not been tested for endometrial cancer. In this study the combination of axitinib and pembrolizumab is experimental because it is not approved by the Food and Drug Administration (FDA).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pembrolizumab With Axitinib in Recurrent Endometrial Cancer With Deficient Mismatch Repair System Post PD1 Exposure: Phase II Trial|
|Estimated Study Start Date :||February 1, 2021|
|Estimated Primary Completion Date :||January 1, 2025|
|Estimated Study Completion Date :||December 1, 2026|
Experimental: Pembrolizumab & axitinib
All participants enrolled will receive pembrolizumab as standard of care (SOC) combined with axitinib. Axitinib will be self-administered orally twice daily at 5 mg. On days when both drugs are administered, axitinib will be administered first, followed by pembrolizumab. Treatment will continue until disease progression or unacceptable grade 3/4 toxicities. For patients with a complete response to therapy, maintenance therapy with both drugs will be continued for 12 months.
200 mg IV day 1 of each cycle every 21 days
5 mg PO BID continuously
- Objective response rate (ORR) at 12 weeks by RECIST 1.1 [ Time Frame: Up to 12 weeks from start of treatment ]
Percent of participants with ORR, defined as those having either a partial or complete response (according to RECIST 1.1) per investigator determination at 12 weeks from the date of study enrollment.
Complete response (CR): Disappearance of all target lesions
Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
- Average overall Survival (OS) [ Time Frame: Assessed up to 60 months ]Average number in months from the date of study enrollment to the date of death (any cause) or last known date of follow up if otherwise lost to follow up.
- Clinical benefit rate [ Time Frame: Up to 12 weeks from start of treatment ]Clinical benefit, defined by percent of participants with ORR and stable disease at 12 weeks
- Number of participants with grade 3 and 4 immune and non-immune related toxicities assessed via NCI CTCAE v.5.03 [ Time Frame: 90 days from end of treatment ]Number of participants with grade 3 and 4 immune and non-immune related toxicities assessed via National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.03
- Average progression-free survival (PFS) [ Time Frame: 12 months from end of treatment ]Average number of months from the date of study enrollment to the date of an event of disease progression (according to RECIST 1.1) per investigator determination or to the date of death (any cause).
- Translational endpoints [ Time Frame: 12 months from end of treatment ]Translational markers to predict resistance and response to therapy. Identify genomic, immune related markers that can predict response and/or resistance to the combined therapy.
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): NCT04197219
|Principal Investigator:||Haider Mahdi, MD||Cleveland Clinic Women's Health Institute|