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

NCT07679841 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: ET25-408
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Vulvar Squamous Cell Carcinoma

Keywords

vulvar squamous cell carcinoma; nivolumab; imiquimod

Outcome Measures

Primary Outcomes (2)

• 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)

  Dose-limiting toxicity (DLT) defined as any adverse event (AE) related to imiquimod and/or nivolumab, occurring during the induction period (first 6 weeks of treatment, i.e., DLT period) and graded according to the NCI-CTCAE V6.0 classification: * Grade 4 non-laboratory AE including skin toxicity; * Grade 3 non-laboratory AE lasting \>14 days despite optimal supportive care with the following exceptions: Influenza-like symptoms and application site reaction related to imiquimod * Any grade 3 or grade 4 laboratory value with clinical symptoms requiring medical intervention or hospitalization, and persisting for more than 14 days; * Any imiquimod site application AE or nivolumab related AE postponing the surgery of at least 14 days * Any other AE evaluated as clinically significant by investigator and sponsor, for instance delaying the nivolumab administration for more than 14 days * Any toxic death, grade 5 AE

  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

  Clinical ORR (objective response rate) as per RECIST 1.1 category documented by calipers using standardized digital photography with reference ruler at the time of surgery

  From Cycle 1 Day 1 to surgery (up to 3 cycles - each cycle is 14 days)

Secondary Outcomes (9)

• Evaluation of the Pathological Response

  At time of surgery

• Rate of positive margin

  At time of surgery

• Rate of positive Sentinel Lymph Node

  Through study completion, up to 3 years

• Rate of patients undergoing RT

  Through study completion, up to 3 years

• Evaluation of Overall Survival (OS)

  From Cycle 1 Day 1 to the date of death from any cause (assessed up to 3 years)

Other Outcomes (5)

• To study the impact of the treatment on the Tumour Microenvironment (TME) immune profile : Changes in CD8 infiltrate

  Through study completion, up to 3 years

• To study the impact of the treatment on the Tumour Microenvironment (TME) immune profile: CD8/FOXP3 ratio

  Through study completion, up to 3 years

• To study the impact of the treatment on the Tumour Microenvironment (TME) immune profile : T effector memory cells

  Through study completion, up to 3 years

Study Arms (1)

Adult female patient with VSCC

EXPERIMENTAL

Patients must have histologically confirmed diagnosis of vulvar squamous cell carcinoma (VSCC).

Drug: Imiquimod 5% cream; Drug: Nivolumab

Interventions

Imiquimod 5% cream DRUG

At the starting dose (DL1) : 5 consecutive days per week for 4 weeks At DL-1: 3 consecutive days per week for 4 weeks

Adult female patient with VSCC

Nivolumab DRUG

At DL1 and DL-1: Administration IV at a dose of 40 mg, every two weeks for 6 weeks (3 doses)

Adult female patient with VSCC

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (3)

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, France

Location

Centre Léon Bérard

Lyon, France

Location

CHU de Saint Etienne

Saint-Priest-en-Jarez, France

Location

MeSH Terms

Interventions

Imiquimod; Nivolumab

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Olivia LE SAUX, MD, PhD

CONTACT

+33469856483; olivia.lesaux@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: July 1, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 1, 2026

Record last verified: 2026-06

Locations

FR (3)