COLOMBE - 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

Sponsor-declared trial summary

Key facts

Sponsor

Centre Leon Berard

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Decision date (initial)

2026-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

PHRC interrégional

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Phase I : Safety run-in: to evaluate the safety of imiquimod and nivolumab combination in adult patients with resectable primary VSCC
Phase 2: to evaluate the clinical efficacy of imiquimod and nivolumab combination in adult patients with resectable primary VSCC

Secondary objectives 3

1. To further evaluate the clinical efficacy of imiquimod and nivolumab combination in the target population
2. To assess the impact of the proposed induction treatment on patient QoL
3. To define the tolerability of the proposed therapeutic strategy

Conditions and MedDRA coding

Vulvar Squamous Cell Carcinoma (VSCC) patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. I1. Female patient ≥ 18 years of age on day of signing informed consent.
2. 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
3. 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
4. I4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
5. I5. Patients with adequate organ function: Absolute Neutrophil Count (ACN) ≥ 1 109/L, Platelets ≥ 100 109/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
6. 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.
7. 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.
8. I8. Patients must be covered by a medical insurance.

Exclusion criteria 10

1. E1. Patients participating in another clinical trial with therapeutic intent.
2. E2. Patients previously treated with any anti-cancer treatment including anti-PD-1, anti-PD-L1, 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).
3. 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)
4. 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.
5. E5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
6. 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.
7. E7. Patients with prior organ or bone marrow transplant.
8. E8. Patients with known active hepatitis B, C, or HIV infection or any active infection requiring systemic therapy.
9. 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.
10. E10. Pregnant or breastfeeding women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety run-in: 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 (see protocol)
2. Phase 2: Clinical ORR as per RECIST 1.1 category documented by calipers using standardized digital photography with reference ruler at the time of surgery

Secondary endpoints 9

1. 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%.
2. Rate of patients with positive margin defined as <8mm
3. Rate of patients with positive Sentinel Lymph Node (SLN)
4. Rate of patients undergoing radiotherapy
5. Surgical complications: see section 7.7 of protocol
6. Overall Survival (OS): 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.
7. 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.
8. Quality of life questionnaire (EORTC QLQ C-30 and QLQ-VU34)
9. Safety: Incidence and severity of AE according to NCI CTCAE V6.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Leon Berard

Sponsor organisation

Centre Leon Berard

Address

28 Rue Laennec

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Centre Leon Berard

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Leon Berard

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications