CETUXIMAB for Recurrent metastatic head and neck squamous cell carcinoma

Stratification factors

• Local PD-L1 CPS (CPS ≥1)

Inclusion criteria

• {"criterion_text":"- 1)\tPatients (male, female, divers) must be ≥18 years of age"}
• {"criterion_text":"- 10) Patient is willing to assess Quality of Life throughout the study"}
• {"criterion_text":"- 11) Adequate hematologic function: Absolute neutrophil count (ANC) ≥1,500/μL, platelets ≥100,000/μL, hemoglobin ≥9.0 g/dL."}
• {"criterion_text":"- 12) Adequate hepatic function: Total bilirubin ≤1.5 × the upper limit of normal (ULN), AST and ALT ≤2.5 × ULN."}
• {"criterion_text":"- 13) Adequate renal function: Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min as calculated by the Cockcroft-Gault formula."}
• {"criterion_text":"- 14) Women of childbearing potential (WOCBP) must have a negative pregnancy test and agree to use highly effective contraception throughout the study and for at least 30 days after last treatment administration. Men must agree to use adequate contraception. a) For female participants: i) Confirmed post-menopausal state (defined as amenorrhea for at least 12 months), or ii) For women of childbearing potential (WOCBP): (1) Negative serum pregnancy test (β‐hCG) before inclusion/randomization, and (2) Practicing a highly effective birth control method (failure rate of less than 1%): I. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral/intravaginal/ transdermal), or II. progestogen-only hormonal contraception associated with inhibition of ovulation (oral/injectable/implantable), or III. intrauterine device (IUD), or IV. intrauterine hormone-releasing system (IUS), or V. bilateral tubal occlusion, or VI. vasectomised partner, or VII. heterosexual abstinence."}
• {"criterion_text":"- 2) Histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is not amenable to curative treatment. Primary tumors in the nasopharynx or cancer of unknown origin are excluded."}
• {"criterion_text":"- 3) Local PD-L1 CPS results for stratification with an expression score ≥1."}
• {"criterion_text":"- 4) Local p16 IHC indicating HPV association for oropharyngeal primary tumor"}
• {"criterion_text":"- 5) Measurable disease based on RECIST 1.1 criteria."}
• {"criterion_text":"- 6) Eastern Cooperative Oncology Group (ECOG) performance status of ≤1."}
• {"criterion_text":"- 7) No prior systemic therapy administered in the recurrent or metastatic setting prior chemoradiation for locally advanced disease is allowed if completed at least 6 months before randomization. Systemic therapy, including anti-PD-(L)1 therapy, given as part of multimodal treatment for locally advanced disease is allowed and must be completed >6 months prior to signing consent. Any toxicity resulting from previous systemic treatment must be resolved or shall not exceed grade 1 based on CTCAE v.5 grading."}
• {"criterion_text":"- 8) Availability of archived tumor tissue (Block or at least 20 slides)"}
• {"criterion_text":"- 9) Documentation of disease progression following curative intended treatment"}
• {"criterion_text":"- 15) Written informed consent obtained from the patient prior to any study-specific procedures."}

Exclusion criteria

• {"criterion_text":"- 1)\tActive or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis."}
• {"criterion_text":"- 10) Participation in another clinical trial with an investigational product within 4 weeks prior to randomization or until End of trial of the individual participant."}
• {"criterion_text":"- 11) Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial"}
• {"criterion_text":"- 12) Organ transplantation: Prior organ transplantation including allogenic stem-cell transplantation."}
• {"criterion_text":"- 13) Cardiovascular disease: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."}
• {"criterion_text":"- 14) Vaccination: Vaccination within 4 weeks of the first dose of study medication and while on trials is prohibited except for administration of inactivated vaccine"}
• {"criterion_text":"- 15) Laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study."}
• {"criterion_text":"- 2)\tPatients not willing to assess QoL at the defined timepoints"}
• {"criterion_text":"- 3)\tActive autoimmune disease requiring systemic immunosuppressive treatment. Patients with controlled autoimmune disease not requiring systemic immunosuppressive treatment including diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Current use of immunosuppressive medication, EXCEPT for the following: a.\tintranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b.\tSystemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c.\tSteroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).”"}
• {"criterion_text":"- 4) Infectious diseases as below: a. Active infection requiring systemic treatment, b. Known HIV infection, unless the participant can meet all the following criteria: i) Documented evidence of plasma HIV-1 RNA persistently <50 copies)/mL confirmed ≤3 months prior to AND at Screening; unless undetectable viral load is defined differently by local guidelines and agreed with the spnsor. In the >3 to 12 months prior to Screening, plasma HIV-1 RNA consistently <50 copies/mL is required; if single/isolated increases ≥50 copies/mL occurred and are thought not to be persistent andnot associated with antiretroviral resistance as per investigator assessment, the participant would be eligible AND ii) CD4 cell count ≥350 cells/mm3 over past 12 months and at Screening (and no measurement <350 cells/mm3 during that period) AND iii) Must be on an uninterrupted combination antiretroviral therapy regimen for at least 3 months prior to Screening, with combination antiretroviral therapy regimen consistent with locally recommended guidelines c. Participants who test positive for HCV antibodies and have positive HCV RNA. d. Untreated chronic hepatitis B or chronic HBV inactive carriers with HBV DNA >500 IU/mL (or >2500 copies/mL) at screening. Patients with chronic hepatitis B (HBsAg-positive) are eligible if they are on adequate antiviral prophylaxis (e.g., entecavir or tenofovir) per local standards and agree to continued monitoring."}
• {"criterion_text":"- 5) Severe uncontrolled systemic disease (e.g., severe chronic obstructive pulmonary disease, severe cardiac disease)."}
• {"criterion_text":"- 6) Participant has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis"}
• {"criterion_text":"- 7) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured."}
• {"criterion_text":"- 8) History of severe hypersensitivity reactions to monoclonal antibodies or any components of the study drugs."}
• {"criterion_text":"- 9) Pregnant or breastfeeding women."}
• {"criterion_text":"- 16) Patients who are institutionalized by order of court or public authority"}
• {"criterion_text":"- 17) Patients who might be dependent on the sponsor/ investigator or the trial site"}

Primary endpoints

• {"endpoint_text":"- Assessment of quality of life (QoL) regarding role functioning at 18 weeks after the initiation of treatment, measured by the standardized QLQ-C30 questionnaire.","definition_or_measurement_approach":"Measured by the standardized EORTC QLQ-C30 questionnaire at 18 weeks after treatment initiation; assesses QoL role functioning domain."}

Secondary endpoints

• {"endpoint_text":"- Progression-Free Survival (PFS): PFS is defined as the time from the date of randomization to the date of the first documentation of objective disease progression or death due to any cause, whichever occurs first. To assess the difference between treatment arm A and treatment arm B in terms of progression-free survival (PFS), an exploratory analysis of the HR including a two-sided 95% CI will be carried out.","definition_or_measurement_approach":"Time from randomization to first documented objective disease progression or death from any cause; exploratory HR analysis with two-sided 95% CI."}
• {"endpoint_text":"- Overall Survival (OS): OS is defined as the time from the date of randomization to the date of death due to any cause. To assess the difference between treatment arm A and treatment arm B in terms of overall survival (OS), an exploratory analysis of the HR including a two-sided 95% CI will be carried out.","definition_or_measurement_approach":"Time from randomization to death from any cause; exploratory HR analysis with two-sided 95% CI."}
• {"endpoint_text":"- Objective Response Rate (ORR): ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR) according to RECIST 1.1 criteria. To assess the difference between treatment arm A and treatment arm B in terms of Objective Response Rate (ORR) an exploratory analysis of the HR including a two-sided 95% CI will be carried out.","definition_or_measurement_approach":"Proportion of patients achieving CR or PR per RECIST 1.1; exploratory comparative analysis with two-sided 95% CI."}
• {"endpoint_text":"- Duration of Response (DOR): DOR is defined as the time from the first documentation of response (CR or PR) to the date of the first documentation of disease progression or death due to any cause, whichever occurs first. To assess whether the difference between treatment arm A and treatment arm B in terms of Duration of Response an exploratory analysis of the HR including a two-sided 95% CI will be carried out.","definition_or_measurement_approach":"Time from first documented response to progression or death; exploratory HR analysis with two-sided 95% CI."}
• {"endpoint_text":"- Exploratory: Quality of Life (QoL): Additional exploratory QoL assessments are conducted using other validated instruments to capture a broader range of patient-reported outcomes which will be assessed with EORTC QLQ H&N35.","definition_or_measurement_approach":"Additional QoL assessed using EORTC QLQ-H&N35 instrument."}
• {"endpoint_text":"- Exploratory: Perceived Stress Questionnaire (PSQ-20): The German version of the Perceived Stress Questionnaire (PSQ-20) by Fliege, Rose, Arck, Levenstein and Klapp (2001) was provided as an instrument for recording stress. The aim is to record the extent of the currently perceived stress factors and the experience of one's own stress on a cognitive and emotional level. It is not the source of the stress that should be stated, but the reaction to it. The factors worry, tension, joy and demands ar","definition_or_measurement_approach":"Perceived stress measured using the German PSQ-20 instrument to assess cognitive and emotional reaction to stress (PSQ-20)."}

Germany

Earliest CTIS Part Ii Submission Date

30-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

18

Number Of Sites

5

Number Of Participants

126

Primary sponsor

Full Name

Charite Universitaetsmedizin Berlin KöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Labor Berlin Charite Vivantes GmbH","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Essen AöR","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Medizinische Hochschule Hannover","duties_or_roles":"code:4","organisation_type":"Educational Institution"}
• {"country":"Germany","full_name":"Universitaetsklinikum Essen AöR (apotheke)","duties_or_roles":"code:14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Aachen AöR (apotheke)","duties_or_roles":"code:14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Klinikum Der Landeshauptstadt Stuttgart gKAöR","duties_or_roles":"code:14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Aachen AöR (central lab?)","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Medizinische Hochschule Hannover (Studien.Apotheke)","duties_or_roles":"code:14","organisation_type":"Educational Institution"}
• {"country":"Germany","full_name":"Klinikum Der Landeshauptstadt Stuttgart gKAöR (other contact)","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Charite Universitaetsmedizin Berlin KöR (sponsor contact)","duties_or_roles":"code:1, code:12, code:6, code:7, code:8","organisation_type":"Hospital/Clinic/Other health care facility"}