Cervical cancer. Cervix carcinoma. PD-L1 checkpoint inhibition. Checkpoint inhibitor. Immunotherapy. Intratumoral. Human Papillomavirus. Cervixcarcinoom. Baarmoederhalskanker. Durvalumab. Immuuntherapie. Intratumoraal. Humaan Papilloma Virus.
Conditions
Interventions
This is a non-randomized, single-arm, open-label, phase I
study. Patients with cervical cancer who are scheduled for
(radical) hysterectomy
with lymph node dissection will be enrolled at the AMC. Two
Sponsors
Academic Medical Center (AMC)
Eligibility
Inclusion criteria
Inclusion criteria: • Age > 18 years at time of study entry • Willing and able to undergo the planned study procedures • World Health Organisation (WHO) performance status of 0 or 1 • Written informed consent • Histologically confirmed cervical cancer of al histological types • Scheduled to undergo (radical) hysterectomy with lymph node dissection • No indication of an active infectious disease: HIV, HCV and HBV negative • No history of autoimmune disease or systematic underlying disease which might affect immunocompetence • Adequate bone marrow function • Subjects must either be of non-reproductive potential or must have a negative urine pregnancy test upon study entry • Ability of subject to understand Dutch language
Exclusion criteria
Exclusion criteria: • Prior treatment with immunotherapy including therapeutic vaccines • Involvement in the planning and/or conduct of the study • Participation in a study with another investigational drug within 30 days prior to enrolment in this study * Major surgery within 28 days before inclusion (conization or biopsy is not major surgery) • Severe cardiac, respiratory, or metabolic disease • Use of oral anticoagulant drugs (except ascal) • Severe infections requiring antibiotics • Lactation or pregnancy • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 • Active or prior documented autoimmune disease within the past 2 years • Active or prior documented inflammatory bowel disease • History of primary immunodeficiency/allogeneic organ transplant/previous clinical diagnosis of tuberculosis/ uncontrolled intercurrent illness • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| To study the effects of locally administered durvalumab on the microenvironment and immune status of the primary tumour and the draining lymph nodes as well as on systemic immunity in these patients by: • characterizing the primary tumour and lymph node microenvironment in pre- and post-treatment biopsies by seven colour fluorescent immunohistochemistry. • analyzing viable tumour- and lymph node material (single-cell suspensions) as well as peripheral blood by 8-10 multi-colour FACS panels before and after durvalumab treatment. • Assessment of frequencies of HPV-specific T cells (HPV-16 E6/E7) by IFNγ elispot assay using an established in vitro stimulation culture protocol or by MHC-I multimer staining. • Monitoring functional Th1/2/17 activity by ex vivo polyclonal stimulation. | — |
Contacts
Public ContactMonica Legdeur
VUmc-Cancer Center Amsterdam, CCA 2 - 48
Outcome results
None listed