Phase II Evaluation of Cetuximab, Platinum, and Taxane-Based Chemotherapy Followed by Avelumab and Cetuximab in PD-L1 CPS ≥1 Recurrent/Metastatic HNSCC
- Trial ID
- 2024-512053-24-00
- Protocol
- AVEC-119
- Sponsor
- Fondazione GONO Plus
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate if the combination of cetuximab plus platinum and taxane-based chemotherapy followed by **avelumab** and cetuximab maintenance can increase the 6-month progression-free survival (PFS) from 40% to 55% in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with a PD-L1 combined positive score (CPS) between 1 and 19. This is clinically relevant as improving PFS can potentially lead to better long-term outcomes and quality of life for patients with this aggressive cancer type.
Secondary objectives include:
- Evaluating the overall survival (OS) of the treatment regimen in the specified patient population.
- Assessing the overall response rate (ORR) to the treatment.
- Determining the safety and tolerability of the treatment regimen.
- Evaluating the duration of response (DOR) to the treatment.
- Investigating whether the activation of immune properties following anti-EGFR based poly-chemotherapy leads to increased sensitivity to immune checkpoint inhibitors (ICIs)-based therapy.
Participants
The clinical trial involves participants diagnosed with **recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)**. The study population includes both male and female subjects, aged 18 years and older, with no vulnerable populations selected. Participants are required to have adequate liver, renal, and bone marrow function, and an ECOG Performance Status of 0-1. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Subjects must have a histologically or cytologically confirmed diagnosis of HNSCC, with measurable disease according to RECIST Criteria 1.1, and should not have received prior systemic therapy in the recurrent/metastatic setting. Lifestyle considerations such as diet and physical activity are not detailed in the trial data. The selection criteria emphasize the need for participants to provide tissue samples and peripheral blood samples, and allow for prior palliative radiotherapy or surgery within four weeks before study entry. The trial aims to evaluate the efficacy of TPE followed by avelumab and cetuximab maintenance in increasing the 6-month progression-free survival rate in patients with PD-L1 CPS between 1 and 19.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of a treatment regimen involving **cetuximab** and **avelumab** for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with a PD-L1 combined positive score (CPS) of ≥1. This is a single-arm, phase II study with an estimated duration extending until October 31, 2029. The trial aims to increase the 6-month progression-free survival (PFS) from 40% to 55% in the target patient population. The study involves a sequence of treatment phases, starting with cetuximab combined with platinum and taxane-based chemotherapy, followed by maintenance therapy with avelumab and cetuximab.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as adequate liver and renal function, confirmed diagnosis of HNSCC, and measurable disease according to RECIST Criteria 1.1. The trial will include regular follow-up visits to monitor treatment response and safety, with assessments of primary and secondary endpoints such as overall survival, overall response rate, and duration of response. The end-of-study visit will conclude the participant's involvement, with a comprehensive evaluation of treatment outcomes.
The expected length of participant involvement is up to 12 months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. Participants must adhere to the study protocol, including providing necessary biological samples and attending scheduled visits, to remain in the trial. The trial is not categorized as low intervention, emphasizing its focus on assessing both efficacy and safety of the investigational treatment regimen.
Treatment
The clinical trial involves the administration of **Erbitux**, a **solution for infusion** containing the active substance **cetuximab**. Cetuximab is a protein-based therapeutic agent classified under the ATC code L01FE01. The pharmaceutical form is a 5 mg/mL solution intended for **intravenous infusion**. The maximum daily dose is 500 mg, with a total maximum dose of 13,000 mg over a treatment period of up to 12 months. The product is re-packaged and labeled specifically for the clinical trial. Compliance with the dosing schedule is monitored to ensure adherence to the protocol.
Additionally, the trial includes the administration of **Avelumab**, a **concentrate for solution for infusion**. Avelumab is a human monoclonal IgG1 antibody, also protein-based, and is administered via **intravenous administration**. The maximum daily dose for Avelumab is 800 mg, with a total maximum dose of 20,800 mg over a 12-month treatment period. Similar to Erbitux, Avelumab is re-packaged and labeled for the purposes of the clinical trial. Participant compliance with the dosing regimen is closely monitored to maintain the integrity of the study.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the evaluation of the 6-month **progression-free survival** (PFS) rate in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treated with cetuximab plus platinum and taxane-based chemotherapy followed by avelumab and cetuximab maintenance. The primary endpoint aims to determine if this treatment regimen can increase the 6-month PFS from 40% to 55% in patients with a PD-L1 combined positive score (CPS) of ≥1 to <19.
Secondary endpoints include the assessment of overall survival (OS), overall response rate (ORR), safety, and duration of response (DOR) for the same treatment regimen. These efficacy parameters will be measured and collected at specified intervals throughout the trial, using validated clinical criteria and laboratory tests. The trial will employ standard oncological assessment tools to ensure accurate and reliable data collection. The analysis of these endpoints will provide comprehensive insights into the efficacy of the treatment regimen in the specified patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects able to sign the informed consent and ≥18 y-old.
- Histologically or cytologically confirmed diagnosis of HNSCC
- Confirmed R/M HNSCC (i.e. oral cavity, oropharynx, larynx, hypopharynx) not suitable for curative loco-regional therapy.
- PD-L1 CPS≥1≤19 (assessment allowed either on primary and/or recurrent/metastatic site of disease).
- Measurable disease according to RECIST Criteria 1.1.
- Subjects should not have had prior systemic therapy administered in the R/M HNSCC setting.
- Systemic therapy that was completed more than 6 months prior to signing consent, if given as a part of multimodal curative treatment for locally advanced disease, is allowed.
- ECOG Performance Status (PS) 0-1.
- Adequate bone marrow function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL.
- Adequate liver function: total bilirubin level < 1.5 X Upper Limit of Normal (ULN) (except from known medical reason not interfering with liver function, such as Gilbert syndrome), AP, GGT <3 x ULN and AST and ALT levels ≤ 2.5 × ULN.
- Adequate renal function: calculated or analyzed creatinine clearance ≥ 30 mL/min. For patients with a CrCl between ≥30 and <60 mL/min, carboplatin will be administered at a dose of AUC 5 every 21 days. If CrCl is ≥60 mL/min, cisplatin can be used instead of carboplatin. (Note: Symptomatic peripheral neuropathy NCI-CTC v5.0 grade ≥2 and / or ototoxicity grade ≥2 (except for cases in which ototoxicity is due to trauma or tumor-related mechanical impairment) and/or creatinine clearance < 60 mL/min are acceptable and they must be approached with carboplatin (instead of cisplatin) since the trial start.)
- All patients deemed eligible by the investigator to receive first-line TPE regardless of their participation in the clinical study, will be considered for inclusion
- Archival or fresh tissue of primary disease (i.e. T and/or N and/or M) OR recurrent/metastatic disease available at baseline (before starting TPE) (available as Formalin-Fixed Paraffin-Embedded - FFPE - or as unstained 10-20 slices).
- Participants have to provide peripheral blood samples (at least 8-10 mL stored in EDTA) according the timing described in the translational part of thef Thecurrent
- Palliative radiotherapy and/or surgery within 4 weeks before the study entry are allowed.
Exclusion Criteria
- Nasopharyngeal, salivary gland, nasal sinus, and non-melanoma skin cancers are not allowed.
- Life expectancy lower than 3 months according to the judgement of trial investigator is not allowed.
- Previous chemotherapy, or biological therapy (i.e. Cetuximab), or immunotherapy administered for R/M setting of HNSCC is not allowed.
- Diagnosis of immunodeficiency or subjects receiving systemic steroid therapy (> 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 30 days prior to start of study treatment which cannot be interrupted.
- Known allergic/hypersensitivity reaction to investigational products or any component in their formulations.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with type I diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
- Any diagnosed and/or treated additional malignancy within 5 years before the study entry with the exception of: curatively treated basal cell carcinoma of the skin, curatively treated squamous cell carcinoma of the skin, curatively treated prostate cancer, curatively resected in situ cervical cancer, and curatively resected in situ breast cancer.
- Subjects with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects’ participation for the full duration of the trial, or is not in the best interest of the subject to participate, according to the opinion of the treating investigator.
- Significant neurologic or known psychiatric or substance abuse disorders that would interfere with cooperation and the requirements of the trial.
- 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.
- Prior organ transplantation including allogenic stem-cell transplantation
- Active uncontrolled infection requiring systemic therapy (i.e. IV antibiotics).
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are NOT ELIGIBLE.
- Hepatitis B virus (HBV) Participants with active infectious diseases (a, b): a) Active hepatitis B infection (1, 2) (i.e. Positive test for hepatitis B virus (HBV) DNA) (1) Participants who are HBsAg positive with NEGATIVE HBV-DNA viral load before trial inclusion are ELIGIBLE. Negativization of HBV DNA viral load can be occurred spontaneously or after antiviral treatment (2) Participants with antecedents of hepatitis B (i.e., anti-hepatitis B core [HBc] positive, HBsAg and hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] NEGATIVE) are ELIGIBLE. b) Active hepatitis C infection (3) (i.e. Positive test for hepatitis C virus (HCV) RNA). (3) Participants who have positive anti-HCV antibodies with NEGATIVE HCV-RNA viral load before trial inclusion are ELIGIBLE. Negativization of HCV RNA viral load can be occurred spontaneously or after antiviral treatment
- Live vaccination within 30 days of planned start of study treatment (inactivated vaccines are allowed).
- Pregnancy (absence of pregnancy must be confirmed by negative serum or urine pregnancy test - ß-HCG - for women of childbearing potential) and/or breastfeeding are not allowed. Subjects of childbearing potential willing to use effective contraceptive method [Pearl Index < 1; e.g. oral contraceptive (pill), hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), sterilization, sexual abstinence] for the entire study duration and 30 days post-dosing.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 31 Oct 2024 | 67 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AVELUMAB | Test | — | INTRAVENOUS ADMINISTRATION | 800 | 12 | SUB180078 |
Erbitux 5 mg/mL solution for infusion | Test | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 500 | 12 | PRD3702716 |