Vulvar Squamous Cell CarcinomaPhase 1/2COLOMBENCT07679841
Safety and Efficacy of Nivolumab and Imiquimod Combination in Vulvar Squamous Cell Carcinoma Patients
A Phase 1/2 study testing Imiquimod 5% cream and Nivolumab in people with Vulvar Squamous Cell Carcinoma, run by Centre Leon Berard at 11 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Vulvar Squamous Cell Carcinoma
- What is being tested?
- Imiquimod 5% cream and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 11 sitesFrance
- Study dates
- Sep 2026to Sep 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
France11 sites
CH de Bourg-en-Bresse
Bourg-en-Bresse
Juliette REURE, MD, +330474454339, jreure@ch-bourg01.fr
Juliette REURE
Centre Jean Perrin
Clermont-Ferrand
Elsa KALBACHER, +33473278080, elsa.kalbacher@clermont.unicancer.fr
Elsa KALBACHER
CHU Clermont-Ferrand
Clermont-Ferrand
Rémi FILLATRE, MD, +33473751635, rfillatre@chu-clermontferrand.fr
Rémi FILLATRE
Groupe Hospitalier Mutualiste de Grenoble
Grenoble
Elise BONNET, MD, +33476285232, elise.bonnet@ghm-grenoble.fr
Elise BONNET, MD
Centre Oscar Lambret
Lille
Anne-Sophie NAVARRO, MD, +33320295959, a-navarro@o-lambret.fr
Anne-Sophie NAVARRO
Centre Léon Bérard
Lyon
Olivia LE SAUX, MD, PHD, +33469856483, olivia.lesaux@lyon.unicancer.fr
Olivia LE SAUX, MD, PhD
HCL - Centre Hospitalier Lyon Sud
Lyon
Nathalie BONNIN, MD, +33478861771, nathalie.bonnin@chu-lyon.fr
Nathalie BONNIN, MD
Hôpital Privé Jean Mermoz
Lyon
Olfa DERBEL, MD, +33437538725, o.derbelmermoz@gmail.com
Olfa DERBEL
Institut Paoli-Calmettes
Marseille
Renaud SABATIER, MD, +33491223847, sabatierr@ipc.unicancer.fr
Renaud SABATIER
CHU de Saint Etienne
Saint-Priest-en-Jarez
Simon NANNINI, MD, PhD, +33477822592, Simon.nannini@chu-st-etienne.fr
Simon NANNINI, MD, PhD
IUCT Oncopole Claudius Regaud
Toulouse
Alejandra MARTINEZ, MD, PhD, +33531155366, martinez.alejandra@iuct-oncopole.fr
Alejandra MARTINEZ
About this study
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
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
- Being tested
- Imiquimod 5% cream, Nivolumab
- Keywords
- vulvar squamous cell carcinoma, nivolumab, imiquimod
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imiquimod 5% creamDrug
At the starting dose (DL1) : 5 consecutive days per week for 4 weeks At DL-1: 3 consecutive days per week for 4 weeks
NivolumabDrug
At DL1 and DL-1: Administration IV at a dose of 40 mg, every two weeks for 6 weeks (3 doses)
| Study group | Role | What they receive |
|---|---|---|
| Adult female patient with VSCC | Experimental | Patients must have histologically confirmed diagnosis of vulvar squamous cell carcinoma (VSCC). Receives: Drug: Imiquimod 5% cream; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: From Cycle 1 Day 1 to surgery (up to 3 cycles - each cycle is 14 days)
Secondary outcomes (9)
Evaluation of the Pathological Response
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%.
Measured: At time of surgery
Rate of positive margin
Rate of patients with positive margin defined as <8mm
Measured: At time of surgery
Rate of positive Sentinel Lymph Node
Rate of patients with positive Sentinel Lymph Node (SLN)
Measured: Through study completion, up to 3 years
Rate of patients undergoing RT
Rate of patients undergoing radiotherapy
Measured: Through study completion, up to 3 years
Evaluation of Overall Survival (OS)
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.
Measured: From Cycle 1 Day 1 to the date of death from any cause (assessed up to 3 years)
Recurrence Free Survival (RFS)
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.
Measured: From Cycle 1 Day 1 to the date of first documented disease recurrence or death (assessed up to 3 years)
Evaluation of surgical complications
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
Measured: From surgery to short term safety visit (occuring 30 days after surgery)
To assess the impact of the proposed induction treatment on patient QoL
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
Measured: From enrollment to Short Term Safety Visit (STSV) (assesed up to 30 days following surgery)
To define the tolerability of the proposed therapeutic strategy
Incidence and severity of AE according to NCI CTCAE V6.0
Measured: Through study completion, up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vulvar Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Centre Leon BerardThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07679841
- Sponsor's protocol ID
- ET25-408
- Acronym
- COLOMBE
- Status last verified
- Jun 2026
- First submitted
- 15 Jun 2026
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07679841
- Acronym / sponsor ID
- COLOMBE / ET25-408
- Conditions
- Vulvar Squamous Cell Carcinoma
- Keywords
- vulvar squamous cell carcinoma, nivolumab, imiquimod
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Centre Leon BerardUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2029 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 1 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adult female patient with VSCC | Experimental | Drug: Imiquimod 5% cream, Drug: NivolumabPatients must have histologically confirmed diagnosis of vulvar squamous cell carcinoma (VSCC). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- I1. Female patient ≥ 18 years of age on day of signing informed consent.
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imiquimod 5% creamAt the starting dose (DL1) : 5 consecutive days per week for 4 weeks At DL-1: 3 consecutive days per week for 4 weeks | Drug | Adult female patient with VSCC |
| NivolumabAt DL1 and DL-1: Administration IV at a dose of 40 mg, every two weeks for 6 weeks (3 doses) | Drug | Adult female patient with VSCC |
Primary outcome
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
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
9 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
Related trials for Vulvar Squamous Cell Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1/2
E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers
HPV-Associated Cervical Carcinoma, HPV-Related Carcinoma
RecruitingPhase 2
E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers
Cervical Cancer, Throat Cancer
RecruitingObservational study
Evaluation of a Point-of-Care, AI-Powered Spectroscopy Device for Triage of Suspicious Vulvar Lesions: A Pilot Study
Vulvar Intraepithelial Neoplasia, HPV-Independent, Vulvar Squamous Cell Carcinoma
Active, not recruitingPhase 2
Agnostic Therapy in Rare Solid Tumors
Urachal Cancer, Parathyroid Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Imiquimod 5% cream and Nivolumab in people with Vulvar Squamous Cell Carcinoma, run by Centre Leon Berard at 11 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Olivia LE SAUX, MD, PhD (+33469856483, olivia.lesaux@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.