Safety and Efficacy of Nivolumab and Imiquimod Combination in Vulvar Squamous Cell Carcinoma Patients

Official title

A Multicentre, Single Arm, Phase 1/2 Study, Aiming to Assess the Safety and Efficacy of Nivolumab and Imiquimod Combination in Vulvar Squamous Cell Carcinoma Patients

Overview

COLOMBE is a multicenter, single arm, phase 1/2 trial designed to evaluate the safety and efficacy of imiquimod cream with IV low dose nivolumab in primary resectable vulvar squamous cell carcinoma patients prior to surgery, leveraging the preoperative "window of opportunity" period, an unavoidable interval due to surgical scheduling.

Interventions

• Drug Imiquimod 5% cream
  At the starting dose (DL1) : 5 consecutive days per week for 4 weeks At DL-1: 3 consecutive days per week for 4 weeks
• Drug Nivolumab
  At DL1 and DL-1: Administration IV at a dose of 40 mg, every two weeks for 6 weeks (3 doses)

Primary outcome measures

• Phase I Safety run-in: Dose-limiting toxicity (DLT) related to imiquimod and/or nivolumab, occurring during the induction period (first 6 weeks of treatment) [Time frame: From Cycle 1 Day 1 to week 6]
• Phase II: To evaluate the clinical efficacy of imiquimod and nivolumab combination in adult patients with resectable primary VSCC [Time frame: From Cycle 1 Day 1 to surgery (up to 3 cycles - each cycle is 14 days)]

Secondary outcome measures (9)

• Evaluation of the Pathological Response [Time frame: At time of surgery]
• Rate of positive margin [Time frame: At time of surgery]
• Rate of positive Sentinel Lymph Node [Time frame: Through study completion, up to 3 years]
• Rate of patients undergoing RT [Time frame: Through study completion, up to 3 years]
• Evaluation of Overall Survival (OS) [Time frame: From Cycle 1 Day 1 to the date of death from any cause (assessed up to 3 years)]
• Recurrence Free Survival (RFS) [Time frame: From Cycle 1 Day 1 to the date of first documented disease recurrence or death (assessed up to 3 years)]
• Evaluation of surgical complications [Time frame: From surgery to short term safety visit (occuring 30 days after surgery)]
• To assess the impact of the proposed induction treatment on patient QoL [Time frame: From enrollment to Short Term Safety Visit (STSV) (assesed up to 30 days following surgery)]
• To define the tolerability of the proposed therapeutic strategy [Time frame: Through study completion, up to 3 years]

Eligibility criteria

Inclusion criteria

I1. Female patient ≥ 18 years of age on day of signing informed consent.

I2. Histologically confirmed primary VSCC, with all of the following characteristics:

• At least 1 lesion that can be measured in at least 1 dimension with ≥ 10 mm in largest diameter
• Clinically stage FIGO I-III (2021 FIGO staging)
• Eligible for primary tumour surgery
• Surgical complexity due to either bulky tumors > 4 cm OR multifocal tumor (defined as the presence of two or more foci of cancer on the vulva), the largest lesion must be ≥ 10 mm and all lesions ≥ 10 mm are designated as "target" lesion(s) for all subsequent tumor evaluations OR any tumor for which a surgical excision would have anatomical or functional consequences deemed significant by the treating surgeon

I3. Availability of a representative formalin-fixed paraffin-embedded (FFPE) sample of the primary tumor tissue (biopsy) with an associated pathology report. This tumor sample must meet the following quality/quantity control criteria: ≥30 % of tumor cells and a tumor surface area ≥ 5mm2

I4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2

I5. Patients with adequate organ function:

• Absolute Neutrophil Count (ANC) ≥ 1 10\^9/L
• Platelets ≥ 100 10\^9/L (without transfusion for platelets within 7 days)
• Hemoglobin ≥ 9 g/dL
• Creatinine clearance according to CKD-EPI ≥ 30 mL/min
• Serum total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert disease for whom a total serum bilirubin ≤ 3 x ULN is acceptable)
• AST and ALT ≤ 3 x ULN

I6. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to C1D1 and must agree to use effective forms of contraception from the time of the negative pregnancy test up to 5 months after the last dose of nivolumab.

I7. Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.

I8. Patients must be covered by a medical insurance.

Exclusion criteria

E1. Patients participating in another clinical trial with therapeutic intent.

E2. Patients previously treated with any anti-cancer treatment including anti-PD-1, anti-PDL1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., CTLA-4, OX 40, CD37).

E3. Patients not respecting the minimal washout period or receiving or anticipation of need during the study of the following medications/procedure:

• Major surgery: 2 weeks
• Live vaccines: 4 weeks
• Systemic corticosteroids (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy: 1 week

E4. Patients with known additional malignancy that is progressing or has required active treatment within the past 3 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin on a location other than the vulva, or carcinoma in situ (e.g. of the breast, cervix or bladder) that have undergone potentially curative therapy are not excluded.

E5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

E6. Patients with evidence of significant uncontrolled infection or concomitant disease, or psychiatric illness/social situations that could affect compliance with the protocol or interpretation of results.

E7. Patients with prior organ or bone marrow transplant.

E8. Patients with known active hepatitis B, C, or HIV infection or any active infection requiring systemic therapy.

E9. Patients with known or suspected active autoimmune disease. Note: Patients with skin disorders (such as vitiligo, psoriasis or alopecia), type I diabetes mellitus, hypothyroidism only requiring hormone replacement or conditions not expected to recur in the absence of an external trigger are eligible.

E10. Pregnant or breastfeeding women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 3 centers

• Groupe Hospitalier Mutualiste de Grenoble — Grenoble
• Centre Léon Bérard — Lyon
• CHU de Saint Etienne — Saint-Priest-en-Jarez

Identifiers

NCT: NCT07679841 · ET25-408

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗