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NCT Number: NCT07679841

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

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.

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Key information

Conditions

Vulvar Squamous Cell Carcinoma

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Groupe Hospitalier Mutualiste de Grenoble, Grenoble, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Nivolumab

Drug

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

Primary outcomes

  1. 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

    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

  2. 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)

    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

Secondary outcomes

  1. Evaluation of the Pathological Response

    Time frame: At time of surgery

    The pathological tumor response (pTR) is defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (<10%), pTR-1 (10%-49%), pTR-2 (≥50%), pTR-3 (100%, complete response). The pTR will be quantified in increments of 10%.

  2. Rate of positive margin

    Time frame: At time of surgery

    Rate of patients with positive margin defined as <8mm

  3. Rate of positive Sentinel Lymph Node

    Time frame: Through study completion, up to 3 years

    Rate of patients with positive Sentinel Lymph Node (SLN)

  4. Rate of patients undergoing RT

    Time frame: Through study completion, up to 3 years

    Rate of patients undergoing radiotherapy

  5. 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)

    Overall survival defined as the time between treatment initiation (C1D1) and death from any cause. Patients still alive at the time of analysis will be censored at the date of last news they are known to be alive.

  6. 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)

    Recurrence Free Survival (RFS): defined as the time from C1D1 to the first documented disease recurrence or death from any cause, whichever occurs first. Patients who are alive and without evidence of recurrence at the time of analysis will be censored at the date of their last disease assessment.

  7. Evaluation of surgical complications

    Time frame: From surgery to short term safety visit (occuring 30 days after surgery)

    The frequency of surgical complications:

    • The percentage of wound breakdown (dehiscence) in the vulva defined as larger than one third of the length of excision.
    • The percentage of wound breakdown (dehiscence) in the groins defined as larger than one third of the length of excision.
    • The percentage of wound infection in the vulva defined as a clinical infection (e.g. the presence of a purulent exudate and/or a positive culture with the presence of erythema, oedema, and localized pain involving skin and subcutaneous tissue) which requires antibiotic therapy
    • The percentage of wound infection in the groins defined as a clinical infection (e.g. the presence of a purulent exudate and/or a positive culture with the presence of erythema, oedema, and localized pain involving skin and subcutaneous tissue) which requires antibiotic therapy.
    • The percentage of patients with lymphocyst formation defined by greater than 4 cm in diameter and confirmed by puncture or ultrasound

  8. 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 assess the impact of the proposed induction treatment on patient QoL with Quality of Life questionnaires:

    • EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30): scores range from 0 to 100, with higher scores indicating better functioning/global health status but worse symptoms
    • EORTC QLQ-VU34 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Vulva Cancer module with 34 questions): scores range from 0 to 100, with higher scores indicating better functioning/global health status but worse symptoms

  9. To define the tolerability of the proposed therapeutic strategy

    Time frame: Through study completion, up to 3 years

    Incidence and severity of AE according to NCI CTCAE V6.0

Other outcomes

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

    Time frame: Through study completion, up to 3 years

    Exploratory analyses in pretreatment tumour biopsies versus surgical specimen will be performed in an effort to understand the impact of the treatment by nivolumab and imiquimod combination on the Tumor Microenvironment (TME) immune profile.

    Exploratory data will be summarized using descriptive statistics (e.g. N, medians, inter-quartile range, and mean, standard deviation, minimum and maximum for continuous variables and frequency counts and percentages for categorical variables). The relationship between TME immune profile and efficacy variables will be assessed using appropriate multivariate models.

    The exploratory analyses will include the following : changes in CD8 infiltrate

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

    Time frame: Through study completion, up to 3 years

    Exploratory analyses in pretreatment tumour biopsies versus surgical specimen will be performed in an effort to understand the impact of the treatment by nivolumab and imiquimod combination on the Tumor Microenvironment (TME) immune profile.

    Exploratory data will be summarized using descriptive statistics (e.g. N, medians, inter-quartile range, and mean, standard deviation, minimum and maximum for continuous variables and frequency counts and percentages for categorical variables). The relationship between TME immune profile and efficacy variables will be assessed using appropriate multivariate models.

    The exploratory analyses will include the following : CD8/FOXP3 ratio

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

    Time frame: Through study completion, up to 3 years

    Exploratory analyses in pretreatment tumour biopsies versus surgical specimen will be performed in an effort to understand the impact of the treatment by nivolumab and imiquimod combination on the Tumor Microenvironment (TME) immune profile.

    Exploratory data will be summarized using descriptive statistics (e.g. N, medians, inter-quartile range, and mean, standard deviation, minimum and maximum for continuous variables and frequency counts and percentages for categorical variables). The relationship between TME immune profile and efficacy variables will be assessed using appropriate multivariate models.

    The exploratory analyses will include the following : T effector memory cells functional analysis (cytokine production of interferon gamma)

  4. To study the impact of the treatment on the Tumour Microenvironment (TME) immune profile: immune checkpoints expression (PD-1, TIGIT, TIM3, CTLA4, CD39)

    Time frame: Through study completion, up to 3 years

    Exploratory analyses in pretreatment tumour biopsies versus surgical specimen will be performed in an effort to understand the impact of the treatment by nivolumab and imiquimod combination on the Tumor Microenvironment (TME) immune profile.

    Exploratory data will be summarized using descriptive statistics (e.g. N, medians, inter-quartile range, and mean, standard deviation, minimum and maximum for continuous variables and frequency counts and percentages for categorical variables). The relationship between TME immune profile and efficacy variables will be assessed using appropriate multivariate models.

    The exploratory analyses will include the following : immune checkpoints expression (PD-1, TIGIT, TIM3, CTLA4, CD39)

  5. To identify biomarkers as predictive factors of efficacy

    Time frame: Through study completion, up to 3 years

    Exploratory analyses to identify biomarkers as predictive factors of efficacy will be performed.

    Exploratory data will be summarized using descriptive statistics (e.g. N, medians, inter-quartile range, and mean, standard deviation, minimum and maximum for continuous variables and frequency counts and percentages for categorical variables). The relationship between biomarker and efficacy variables will be assessed using appropriate multivariate models.

    The biomarkers analyzed will include the following :

    • HPV dependent vs HPV independent VSCC (p16 IHC status)
    • TP53 mutation
    • TME immune profile
    • PD-L1 expression

Study contacts

Contact information is provided by the study sponsor or research team.

Olivia LE SAUX, MD, PhD

CONTACT

[email protected]

+33469856483

Sponsors and collaborators

Lead sponsor

Centre Leon Berard

Other

Registry information

Official study 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

Acronym: COLOMBE

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Jul 1, 2026
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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