We aim to determine feasibility, safety and efficacy of TDLN-targeted immune checkpoint inhibition in different doses (nivolumab) in patients with cervical cancer.
Objective: We aim to determine feasibility, safety and efficacy of TDLN-targeted immune checkpoint inhibition in different doses (nivolumab) in patients with cervical cancer. Trial design: This is a single-arm, single-center phase 1 study to evaluate the feasibility and dose-finding of neoadjuvant nivolumab in newly diagnosed cervical cancer patients. Two 3-weekly subcutaneous administrations of nivolumab (5, 10, 15, or 30 mg) will be given in the inner-upper thigh, targeting the tumor-draining lymph nodes. Treatment will occur between diagnosis and standard-of-care surgery, followed by adjuvant therapy. The dose levels are based on the established bioavailability and previous reports of biological activity. Subjects participate in the study for 11 weeks with late follow-up visits after 3 and 6 months. Trial population: The study will include female patients aged 18 and older with newly diagnosed cervical cancer (FIGO stage \< IB3) who are eligible for standard-of-care surgery. Participants must not be pregnant or breastfeeding and must provide informed consent. Key exclusion criteria include prior systemic immunotherapy, recent systemic anti-cancer therapy, live vaccines, active infections, autoimmune diseases requiring treatment, known CNS metastases, and other malignancies within the last three years. Patients with hypersensitivity to nivolumab or severe comorbidities, including active pneumonitis or immunodeficiency, will be excluded. Intervention: Nivolumab (5, 10, 15, or 30 mg), subcutaneous Q3W for a total of 2 administrations per patient, integrated into standard-of-care protocol prior to surgery. Based on the well-established timelines, the interval between diagnosis and standard-of-care (SoC) surgery is sufficient to treat patients with two administrations of nivolumab without interfering with standard treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Subcutaneous injection of nivolumab
University Medical Centre Groningen
Groningen, Netherlands
RECRUITINGFeasibility: Proportion of participants undergoing planned standard surgical treatment after 2 cycles of TDLN-targeted neoadjuvant ICI without treatment-related delay or cancellation.
Feasibility will be assessed as the proportion of participants who complete 2 cycles of neoadjuvant TDLN-targeted immune checkpoint inhibition and subsequently undergo planned standard surgical treatment without treatment-related delay or cancellation.
Time frame: Through study completion, an average of 2 months per patient
Pathologic response rate
At least one partial pathologic response (pPR) must be observed, irrespective of dose level. All further pathologic responses will be reported on using descriptive statistics for the estimated percentage of viable remaining cancer cells at the end of the study period and defined based on work in other cancers such as melanoma, breast and colorectal cancer with: * pPR - \<90% vital tumor cells * pNCR - \<10% vital tumor cells in the tumor * pCR - the complete absence of viable cancer cells in the tumor
Time frame: Tumor tissue will be collected during standard-of-care surgery
Safety and toxicity
Adverse events be monitored in the current trial using GCP guidelines. All AEs will be followed until they have abated, or until a stable situation has been reached. The reporting period for all AEs begins with signing the ICF. Patients will visit the hospital in weeks 12, 21 and 33 to monitor potential long-term effects of the nivolumab.
Time frame: Through study completion, an average of 2 months per patient
Radiologic responses
MRI will be performed at baseline (SoC diagnostic workup) and will be compared to MRI performed prior to surgery (week 11). Tumor response will be classified according to RECIST 1.1: * Complete Response (CR): Disappearance of all target lesions. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest-sum-on-study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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Time frame: MRI is before start of study drug and 3 weeks after the second/last dose of study drug