IPILIMUMAB for Head and neck squamous cell carcinoma | Oral cavity squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- 18 years of age or older\n- Patients willing and able to understand the Dutch study information and protocol requirements and comply with the treatment/intervention schedule, scheduled visits, and other requirements of the study.\n- Primary advanced oral cavity squamous cell carcinoma (HNSCC) o Stage III-IVA according to TNM version 8.0 of the UICC/AJCC staging manual.\n- Primary tumour site: o Malignant neoplasm of other and unspecified parts of tongue (C02.0-C02.3, C02.8-9) o Malignant neoplasm of gum (C03) o Malignant neoplasm of floor of mouth (C04) o Malignant neoplasm of hard palate (C05.0, C05.8-9) o Malignant neoplasm of other and unspecified parts of mouth (C06)\n- Indication for SOC*\n- No prior systemic oncological therapy\n- No prior radiotherapy to the head and neck\n- No immunosuppression\n- World Health Organisation (WHO) performance status of 0-2\n- Screening laboratory values must meet the following criteria: o WBC ≥ 2.0x109 /L o Neutrophils ≥1.5x109 /L o Platelets ≥100 x109 /L o Hemoglobin ≥5.5 mmol/L o Creatinine ≤1.5x upper limit of normal (ULN) o AST ≤ 1.5 x ULN o ALT ≤ 1.5 x ULN o Bilirubin ≤1.5 X ULN (except patients with Gilbert Syndrome, who are eligible when total bilirubin < 3.0 mg/dL) o Women of child-bearing potential (WOCBP) must use appropriate method(s) of con-traception. They should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required time for nivolumab to undergo five x T1/2, ipilimumab has a much shorter T1/2) after the last dose of the IMP. o WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) prior to the start of ICB."}

Exclusion criteria

• {"criterion_text":"- Inoperable OSCC (Stage IVB)\n- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids (up to 10 mg of prednisone per day is allowed)\n- Patients who are pregnant or breastfeeding\n- History of allergy to study drug components and/or history of severe hypersensitivity to any monoclonal antibody\n- Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion\n- Distantly metastasized (Stage IVC) OSCC\n- Prior irradiation in the head and neck area.\n- Prior anti-PD(L)1 or anti-CTLA4 immune checkpoint-blockade.\n- Prior diagnosed malignancies, except malignancies with a 2 year survival rate of over >90% (eg. certain skin cancers, low-grade prostate carcinoma) and where treatment does not interfere with the treatment of patients included in this trial.\n- Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)\n- Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C antibody (HCV Ab)\n- Subjects with any active autoimmune disease or a documented history of autoimmune disease, except: o Subjects with vitiligo o Resolved childhood asthma/atopy o Residual hypothyroidism due to an autoimmune condition requiring only hormone replacement o Psoriasis without the need for systemic treatment o Any condition not expected to recur in the absence of an external trigger.\n- Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity or AEs"}

Primary endpoints

• {"endpoint_text":"- The percentage of patients in arm A with a CCR and organ preservation of the face and oral cavity at 24 months of FU*. Success is defined with a lower bound of the 95% CI >10%.","definition_or_measurement_approach":"CCR (complete clinical response) assessed at 24 months follow-up; success defined as lower bound of the 95% confidence interval > 10%."}
• {"endpoint_text":"- Non-inferiority of arm A compared to arm B in Recurrence Free Survival (RFS) after a minimum FU of 24 months since randomisation for each patient. An event is defined as disease progression to unresectable disease before surgery or before adjuvant (C)RT, OR recurrent disease after treatment, OR death due to any cause.","definition_or_measurement_approach":"Recurrence Free Survival (RFS) measured from randomisation with minimum follow-up of 24 months; event defined as progression to unresectable disease before surgery or before adjuvant (C)RT, OR recurrent disease after treatment, OR death from any cause."}

Secondary endpoints

• {"endpoint_text":"- The CCR rate in ARM A at 12 and 18 months","definition_or_measurement_approach":"CCR assessed in Arm A at 12 and 18 months follow-up."}
• {"endpoint_text":"- To assess the difference in Qol between Arm A and B on all domains of the EORTC QLQ H&N43 and the EORTC QLQ-C30, EQ-5D-5L, HADS. • And between the responders in Arm A vs Arm B. • And between the non-responders of Arm A vs Arm B. • And between responders and non-responders of arm A","definition_or_measurement_approach":"Quality of life measured using EORTC QLQ-H&N43, EORTC QLQ-C30, EQ-5D-5L, and HADS across specified comparisons."}
• {"endpoint_text":"- Compare other survival endpoints between Arm A and B (Locoregional control (LRC), dis-tant metastasis free survival (DMFS), Disease specific survival (DSS), Recurrence Free Sur-vival (RFS), Event Free Survival (EFS) and Overall survival (OS)) at 12, 18 and 24 months FU","definition_or_measurement_approach":"Multiple time-to-event survival endpoints (LRC, DMFS, DSS, RFS, EFS, OS) assessed at 12, 18 and 24 months follow-up."}
• {"endpoint_text":"- Compare AEs and ir-AEs in both arms using the CTCAE v5.0 and Clavien-Dindo up to 100 days after last treatment (immunotherapy, surgery or adjuvant (C)RT)","definition_or_measurement_approach":"Adverse events and immune-related AEs graded by CTCAE v5.0 and surgical complications by Clavien-Dindo up to 100 days after last treatment."}
• {"endpoint_text":"- Cost-effectiveness of ARM A will be compared to ARM B in terms of incremental costs and quality adjusted life years","definition_or_measurement_approach":"Health economic comparison using incremental costs and QALYs."}
• {"endpoint_text":"- Treatment duration and stops of ARM A will be compared to ARM B.","definition_or_measurement_approach":"Compare duration of oncological treatment and treatment interruptions between arms."}
• {"endpoint_text":"- Extent of surgery (type and hours), RT( days and total Gy), chemotherapy (typaeand cumulative dose), days of admission on the ward, visits, other interventions, etc. • Comparison between ARM A and B • Between the responders in Arm A vs Arm B. • And between the non-responders of Arm A vs Arm B. • And between responders and non-responders of arm A","definition_or_measurement_approach":"Clinical resource and intervention metrics (surgical extent/duration, RT days and total Gy, chemo type/cumulative dose, admission days, visits) compared between arms and responder subgroups."}

Netherlands

Earliest CTIS Part Ii Submission Date

27-11-2025

Latest Decision Or Authorization Date

12-12-2025

Processing Time Days

15

Number Of Sites

7

Number Of Participants

308

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands