A Phase II Randomized Clinical Trial Comparing Two Cycles Versus Four Cycles of Combination Therapy with Cetuximab, Avelumab, Cisplatin, and Docetaxel in Patients with Recurrent Metastatic Head and Neck Cancer - AVETUX-HN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09], Diseases [C] - Neoplasms [C04]

Trial duration

15 Dec 2025 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-521738-27-00

WHO UTN

U1111-1326-5486

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Efficacy

To compare the quality of life at 18 weeks after treatment initiation between two cycles and four cycles of combination therapy with Cetuximab, Avelumab, Cisplatin, and Docetaxel.

Secondary objectives 6

1. To estimate the difference in PFS between the two treatment arms
2. To estimate the difference in OS between the two treatment arms
3. To estimate the difference in ORR between the two treatment arms
4. To estimate the difference in DOR between the two treatment arms
5. Exploratory: To evaluate QoL.
6. Exploratory: To evaluate perceived Stress in both treatment groups.

Conditions and MedDRA coding

Recurrent Metastatic Head and Neck Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1) Patients (male, female, divers) must be ≥18 years of age
2. 10) Patient is willing to assess Quality of Life throughout the study
3. 11) Adequate hematologic function: Absolute neutrophil count (ANC) ≥1,500/μL, platelets ≥100,000/μL, hemoglobin ≥9.0 g/dL.
4. 12) Adequate hepatic function: Total bilirubin ≤1.5 × the upper limit of normal (ULN), AST and ALT ≤2.5 × ULN.
5. 13) Adequate renal function: Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min as calculated by the Cockcroft-Gault formula.
6. 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.
7. 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.
8. 3) Local PD-L1 CPS results for stratification with an expression score ≥1.
9. 4) Local p16 IHC indicating HPV association for oropharyngeal primary tumor
10. 5) Measurable disease based on RECIST 1.1 criteria.
11. 6) Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
12. 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.
13. 8) Availability of archived tumor tissue (Block or at least 20 slides)
14. 9) Documentation of disease progression following curative intended treatment
15. 15) Written informed consent obtained from the patient prior to any study-specific procedures.

Exclusion criteria 17

1. 1) Active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
2. 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.
3. 11) Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
4. 12) Organ transplantation: Prior organ transplantation including allogenic stem-cell transplantation.
5. 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.
6. 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
7. 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.
8. 2) Patients not willing to assess QoL at the defined timepoints
9. 3) Active 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. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).”
10. 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.
11. 5) Severe uncontrolled systemic disease (e.g., severe chronic obstructive pulmonary disease, severe cardiac disease).
12. 6) Participant has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
13. 7) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
14. 8) History of severe hypersensitivity reactions to monoclonal antibodies or any components of the study drugs.
15. 9) Pregnant or breastfeeding women.
16. 16) Patients who are institutionalized by order of court or public authority
17. 17) Patients who might be dependent on the sponsor/ investigator or the trial site

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Assessment of quality of life (QoL) regarding role functioning at 18 weeks after the initiation of treatment, measured by the standardized QLQ-C30 questionnaire.

Secondary endpoints 6

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Hindenburgdamm 30, Lichterfelde Lichterfelde

City

Berlin

Postcode

12203

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

PD Dr. Konrad Klinghammer

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

PD Dr. Konrad Klinghammer

Third parties 10

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

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