NCT06856213

Study of Cetuximab Plus/Minus Weekly Paclitaxel After Progression To First-Line Pembrolizumab Plus Platinum-5FU in Subjects With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck.

TTCC-2022-02: A Phase II, Multicenter, Randomized Study of Cetuximab Plus/ Minus Weekly Paclitaxel After Progression To First-Line Pembrolizumab Plus Platinum-5FU in Subjects With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (ERBIOTAX)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 65 (estimated)
• Sponsor: Grupo Español de Tratamiento de Tumores de Cabeza y Cuello · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Squamous cell carcinoma of the head and neck (SCCHN) arises from epithelial cells and occurs in the oral cavity, pharynx and larynx. SCCHN is the seventh most common cancer worldwide with an annual incidence of approximately 90.000 cases per year in Europe. Recurrent / metastatic SCCHN remains a grievous diagnosis and optimal treatment options after progression to first-line ICI treatment are not determined yet. Previous reports showed that cetuximab plus paclitaxel after progression to ICI therapy may have an enhanced activity as second line after ICI therapy ERBIOTAX is multi-center, open-label, randomized, non-comparative two-arm, phase 2 trial Investigator Initiated Study. The primary study aims is to evaluate the efficacy of weekly cetuximab combined with paclitaxel (Arm A) or cetuximab monotherapy (Arm B) after progression to pembrolizumab plus platinum / 5-FU. The efficacy of treatment will be assessed through objective response rate (ORR). Patients will be randomized in a 2:1 ratio to ERBITAX (cetuximab + paclitaxel) and cetuximab, respectively, assigning 2 patients to Arm A and 1 patient to Arm B out of 3 patients. No stratification for the randomization process is planned as this is a non-comparative study. A total of 65 evaluable patients will be included in the trial; 41 in Arm A and 24 in Arm B. The main hypothesis is that treatment with the cetuximab +/- paclitaxel regimen maybe more effective after immune checkpoint inhibitors (ICI) failure in patients with recurrent/metastatic head and neck squamous cell carcinoma.

Detailed description

1. Objectives Primary Objective -The study aims to evaluate the efficacy of weekly cetuximab combined with paclitaxel (Arm A) or cetuximab monotherapy (Arm B) after progression to pembrolizumab plus platinum / 5-FU. The efficacy of treatment will be assessed through objective response rate (ORR). Secondary Objectives * To evaluate clinical outcomes such as disease control rate (DCR), progression free survival (PFS), and overall survival (OS). * To evaluate the quality of life of patients with recurrent/metastatic head and neck squamous cell carcinoma treated with cetuximab and paclitaxel or cetuximab monotherapy. * To evaluate safety of the intended treatment regimen based on the frequency and severity of adverse events and Treatment-emergent adverse events (TEAEs) assessed by NCI CTCAE v5.0. Exploratory objectives * To evaluate the genomic/transcriptomic/proteomic alterations in baseline and on-treatment tumor samples. * To evaluate ctDNA dynamics between baseline and on-treatment plasma samples. Immunophenotyping of tumor samples. 2. Endpoints Primary Endpoint Confirmed objective response rate (ORR) according to RECIST V1.1 criteria Secondary Efficacy Endpoints * Disease Control Rate (DCR) . Median PFS * Median OS * Health-related quality of life (HRQoL), assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) version 3, the head and neck specific module QLQ-H\&N35 and EuroQol EQ-5D Secondary Safety Endpoints * Frequency and severity of adverse events and Treatment-related adverse events (TRAEs) assessed by NCI CTCAE v5.0 * Rate of completion of C2D8, C4D8 and C6D8 of Cetuximab +/- Paclitaxel Exploratory endpoints * Presence of genomic/transcriptomic/proteomic alterations * ctDNA dynamics through study treatment * Immunophenotype of tumor and blood samples 3. Study Design The ERBIOTAX trial is a multicenter, open-label, randomized, non-comparative two-cohort, Phase II clinical trial of cetuximab either as monotherapy or in combination with paclitaxel in patients with SCCHN progressing on or after pembrolizumab plus platinum-based chemotherapy as first-line combination therapy. Additional details on the eligibility criteria of the study are found in protocol. The primary aim of the study is to evaluate the efficacy of weekly cetuximab combined with paclitaxel (Arm A) or cetuximab monotherapy (Arm B) after progression to pembrolizumab plus platinum / 5-FU. The efficacy of treatment will be assessed through ORR. The design includes a screening phase in which patient eligibility is addressed, a treatment phase with cetuximab, either as a single agent or combined with paclitaxel, and a follow-up phase. Signed informed consent form (ICF) will be obtained prior to the start of the specified screening window. Procedures conducted as part of the subject's routine clinical management (e.g., blood count determinations and imaging studies) prior to signing of ICF may be used for screening or for defining baseline data, provided these procedures are conducted as specified in the protocol.Patients will be randomized in a 2:1 ratio to ERBITAX and cetuximab, respectively. 4. Study population The trial will include 65 evaluable patients with recurrent/metastatic head and neck squamous cell carcinoma (41 in group A and 24 in group B). 5. Study Treatments Patients will be randomized (2:1 ratio) to cetuximab + paclitaxel (ERBITAX) (Arm A) or to cetuximab monotherapy (Arm B). The complete schedule of treatment is detailed below: ARM A: Cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 + Paclitaxel 80mg/m2 (D1, D8 and D15 each 3-weeks cycle) for 4 cycles. Then, monotherapy maintenance with cetuximab at a dose of 500 mg/m2 will be administered biweekly (D1 and D15; Q4W) until disease progression or death, unacceptable toxicity or patient withdrawal of consent\*. ARM B: Cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 (D1, D8 and D15 each 3-weeks cycle) for 4 cycles. Then, maintenance with cetuximab at a dose of 500 mg/m2 will be administered biweekly (D1 and D15; Q4W) until disease progression or death, unacceptable toxicity or patient withdrawal of consent.

Conditions

• Recurrent / Metastatic Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Cetuximab	Cetuximab 250 mg/m2 will be administered as an intravenous infusion over 60 minutes. Cetuximab loading dose is 400 mg/m2 infusion and will be administered over 120 minutes. During maintenance, cetuximab at 500 mg/m2 will be administered as an intravenous infusion over 120 minutes.
DRUG	Paclitaxel	Paclitaxel at a dose of 80 mg/m² will be administered after cetuximab as an intravenous infusion over 60 minutes weekly.

Timeline

• Start date: 2025-06-18
• Primary completion: 2028-10-01
• Completion: 2028-10-01
• First posted: 2025-03-04
• Last updated: 2025-08-21

Locations

11 sites across 1 country: Spain