Single low-dose DURValumab IntraTumorally injected in cervical cancer: safety, toxicity and effect on the primary tumour- and lymph node microenvironment.
Completed
- Conditions
- Cervical cancer. Cervix carcinoma. PD-L1 checkpoint inhibition. Checkpoint inhibitor. Immunotherapy. Intratumoral. Human Papillomavirus. Cervixcarcinoom. Baarmoederhalskanker. Durvalumab. Immuuntherapie. Intratumoraal. Humaan Papilloma Virus.
- Registration Number
- NL-OMON29031
- Lead Sponsor
- Academic Medical Center (AMC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 24
Inclusion Criteria
• Age > 18 years at time of study entry
• Willing and able to undergo the planned study procedures
Exclusion Criteria
• Prior treatment with immunotherapy including therapeutic vaccines
• Involvement in the planning and/or conduct of the study
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method This is a phase-I study and therefore we have the following primary objective: to study clinical safety and tolerability a of locally administered single dose of durvalumab in cervical cancer patients scheduled to (radical) hysterectomy with lymph node dissection. This method of administration has not been tested before in cervical cancer patients. We expect the occurrence and severity of AEs to be much lower as compared to intravenous administration of durvalumab. Safety will be evaluated through the analysis of Adverse Events (AE), laboratory tests, physical examination, vital signs and performance status. The Common Terminology Criteria for Adverse Events (CTCAE) v4.03 will be used for the assessment of adverse events. The primary goal of the study is to determine the maximum tolerated dose (MTD) of local injection of durvalumab in cervical cancer patients.
- Secondary Outcome Measures
Name Time Method To study the effects of locally administered durvalumab on<br>the microenvironment and immune status of the primary<br>tumour and the draining lymph nodes as well as on systemic<br>immunity in these patients by:<br /><br>• characterizing the primary tumour and lymph node<br>microenvironment in pre- and post-treatment biopsies by<br>seven colour fluorescent immunohistochemistry.<br /><br>• analyzing viable tumour- and lymph node material<br>(single-cell suspensions) as well as peripheral blood by 8-10<br>multi-colour FACS panels before and after durvalumab<br>treatment.<br /><br>• Assessment of frequencies of HPV-specific T cells<br>(HPV-16 E6/E7) by IFNγ elispot assay using an established in<br>vitro stimulation culture protocol or by MHC-I multimer<br>staining.<br /><br>• Monitoring functional Th1/2/17 activity by ex vivo<br>polyclonal stimulation.