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.

NCT06856213 | Recruiting Phase 2 DMC

• 2 other identifiers: TTCC-2022-022024-514953-31-00
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Recurrent / Metastatic Head and Neck Squamous Cell Carcinoma

Keywords

Squamous Cell Carcinoma of the Head and Neck; SCCHN; Cetuximab; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Confirmed objective response rate (ORR) according to RECIST V1.1 criteria

  Objective response rate (ORR) will be Assessed by the investigator through imaging follow-up (CT scan/MRI) using RECIST 1.1. This will be considered as the percentage/proportion of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the study period. Objective responses must be confirmed in a second CT scan performed 4 weeks later (+ 7 day window). Objective responses will be assessed locally by the investigator according to RECIST, version 1.1, and indicating the change in size of tumors as compared with baseline, at the first dose of study treatment.

  Throughout the study period, approximately 24 months

Secondary Outcomes (5)

• DCR (Disease Control Rate)

  Throughout the study period, approximately in a time frame 6 months from the start of treatment

• Progression-free surviva (PFS)

  Throughout the study period, at week 8 and every 12 weeks thereafter from start treatment for up to approximately 24 months

• Overall survival (OS)

  Throughout the study period, approximately 24 months from start treatment

• Frequency and severity of adverse events and Treatment-related adverse events (TRAEs)

  Throughout the study period, approximately a time frame of 2 years from start treatment

• Health-related quality of life (HRQoL)

  Throughout the study period, approximately a time frame of 2 years from start treatment

Study Arms (2)

ARM A (Cetuximab+Paclitaxel)

EXPERIMENTAL

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

Drug: Cetuximab; Drug: Paclitaxel

ARM B (Cetuximab)

EXPERIMENTAL

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.

Drug: Cetuximab

Interventions

Cetuximab DRUG

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.

ARM A (Cetuximab+Paclitaxel); ARM B (Cetuximab)

Paclitaxel DRUG

Paclitaxel at a dose of 80 mg/m² will be administered after cetuximab as an intravenous infusion over 60 minutes weekly.

ARM A (Cetuximab+Paclitaxel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Informed consent
• Signed written and voluntary informed consent.
• Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Age \> 18 years old. Disease characteristics
• Have histologically confirmed diagnosis of head and neck squamous cell carcinoma.
• The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
• Known Human papillomavirus (HPV) status in oropharyngeal primaries and tested by p16 and/or HPV DNA testing by ISH or PCR. Local testing is acceptable.
• Have confirmed disease progression per RECIST 1.1 on or after receiving platinum / 5-FU and pembrolizumab as first-line therapy for recurrent/metastatic disease. Patients must have measurable disease assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) based on RECIST 1.1 as assessed by the local site investigator/radiology. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• All patients must provide a tumor biopsy obtained prior to the start of cetuximab +/- paclitaxel. A newly obtained biopsy -after progression to pembrolizumab + platinum-based chemotherapy - of a tumor lesion not previously irradiated for central biomarker analysis prior to start of study treatment is strongly preferred, but an archival sample may be acceptable upon discussion with the sponsor, if obtained in the prior 12 months.
• Note: Fine needle aspirate \[FNA\] is not adequate. Repeat samples may be required if adequate (quality and quantity) tissue is not provided. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides
• Patient characteristics
• Have a performance status of 0 or 1 on the ECOG Performance Scale
• Patients must have adequate organ function as determined by the following. Screening labs should be performed within -7 days of treatment initiation:
• a. Hematology
• Absolute neutrophils \> 1.5 x 109/L

You may not qualify if:

• Patients with tumors of the head and neck region, arising from the nasopharynx, nasal cavity, paranasal sinuses, salivary glands, skin, unknown primary site.
• Patients not treated or not progressing to pembrolizumab + platinum / 5-FU as the first line prior to their enrollment in the study. Progression to platinum / 5-FU plus pembrolizumab or other antiPD-(L)1 agents in combination with other immunotherapies including but not limited to other checkpoint regulatory monoclonal/bispecific antibodies such as anti CTLA-4, anti LAG-3 , anti TIGIT or anti TIM-3 may be allowed upon discussion with the sponsor.
• Any previous treatment with paclitaxel and/or cetuximab in the recurrent or metastatic setting.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or CT scan) for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g. tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator.
• History of another primary malignancy, except for:
• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence,
• Adequately treated non-melanoma skin cancer without evidence of disease,
• Adequately treated carcinoma in situ without evidence of disease.
• Any previous surgical treatment of the current cancer (except for a diagnostic biopsy) and no major surgery within 28 days prior to study treatment initiation. Performance of a tracheostomy or placement of a percutaneous gastrostomy tube within the 28 days prior to study treatment initiation will be allowed if the patient is clinically stable with no complications derived from those interventions.
• Focal radiotherapy (RT) with palliative intent that is not completed 2 weeks prior to the first dose of Cetuximab +/- Paclitaxel.
• History of allergic or hypersensitivity reactions to any study drugs or their excipients.
• History of allogeneic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of study treatment initiation or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
• Any concurrent chemotherapy, biologic, immunologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.

Sponsors & Collaborators

• Grupo Español de Tratamiento de Tumores de Cabeza y Cuello: lead

Study Sites (11)

Instituto Catalán de Oncología - Hospital Duran i Reynals

Barcelona, Barcelona, 08908, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla (Santander)

Santander, Cantabria, 39008, Spain

RECRUITING

Centro Oncológico de Galicia (La Coruña)

A Coruña, La Coruña, 15009, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre (Madrid)

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Infanta Leonor (Madrid)

Vallecas, Madrid, 28031, Spain

RECRUITING

Complejo Hospitalario de Navarra (Pamplona)

Pamplona, Navarre, 31008, Spain

RECRUITING

Complejo Hospitalario de Salamanca (Salamanca)

Salamanca, Salamanca, 37007, Spain

RECRUITING

Hospital Universitario de Canarias (La laguna)

San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38320, Spain

RECRUITING

Hospital Universitario Virgen del Rocío (Sevilla)

Seville, Sevilla, 41013, Spain

RECRUITING

Hospital Universitario Virgen de Valme (Sevilla)

Seville, Sevilla, 41014, Spain

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Santiago Cabezas, M.D., Ph.D.

  Hospital San Carlos, Madrid

  STUDY CHAIR

• Marc Oliva, M.D., Ph.D.

  ICO-Hospitalet

  STUDY CHAIR

• Neus Basté, M.D

  ICO-Badalona

  STUDY CHAIR

Central Study Contacts

Federico Nepote, M.D., PhD.

CONTACT

+34 93 434 44 12; investigacio@mfar.net

Marisa Duran Senior Clinical research proyect manager (TTCC)

CONTACT

0034690756714; mduran@ttccgrupo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, open-label, randomized, non-comparative two-arm, phase 2 trial; Investigator Initiated Study (IIS). Patients will be randomized (2:1 ratio) to cetuximab + paclitaxel (ERBITAX) (Arm A) or to cetuximab monotherapy (Arm B).

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: March 4, 2025
• Study Start: June 18, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: August 21, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (11)