Study to Assess the Efficacy and Safety of Nivolumab in Combination With Paclitaxel in Subjects With Head and Neck Cancer Unable for Cisplatin-based Chemotherapy (NIVOTAX)

NCT04282109 | Completed Phase 2 Results DMC

• 2 other identifiers: TTCC-2019-01/CA209-7HE2019-002922-60
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 21

Brief Summary

Chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma is palliative and usually platinum based, and the patients often present with poor physical condition. Consequently, many of them are not able to withstand a platinum-based chemotherapy. The addition of taxanes to the armamentarium of drugs improve the outcome in this group of patients. An alternative and better tolerated regimen for these patients is paclitaxel in combination with cetuximab, included the in guidelines of the Spanish Society of Medical Oncology. Recently, new treatments such as immune-checkpoint inhibitors have shown promising activity and good tolerability in patients with recurrent or metastatic head and neck squamous cell carcinoma and has been included in the recently published guidelines from the Society for Immunotherapy of Cancer. Nivolumab (anti-PD1) has been approved for patients progressing on or after platinum-based therapy, as it clearly impacts on overall survival. This randomized phase II study will evaluate the efficacy of nivolumab plus paclitaxel for first-line treatment of recurrent or metastatic HNSCC in the platinum ineligible and platinum refractory settings. Control arm will be paclitaxel in combination with cetuximab, treatment included in the guidelines of the Spanish Society of Medical Oncology.

Conditions

Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Keywords

Head and neck cancer; Squamous cell carcinoma; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Two Years Overall Survival (OS)

  OS is defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive.

  2 years

Secondary Outcomes (21)

• Progression Free Survival (PFS)

  Up to 45 months

• Overall Response Rate (ORR)

  Up to 2 years

• Disease Control Rate (DCR)

  Up to 2 years

• Duration of Response (DoR)

  Up to 45 months

• 6-months Progression-free Survival Rate

  6 months

Study Arms (2)

Arm 1

EXPERIMENTAL

NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab)

Drug: Nivolumab + Paclitaxel

Arm 2

ACTIVE COMPARATOR

ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab)

Drug: Cetuximab + Paclitaxel

Interventions

Nivolumab + Paclitaxel DRUG

Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Arm 1

Cetuximab + Paclitaxel DRUG

Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Arm 2

Eligibility Criteria

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

You may qualify if:

• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care.
• Histologically confirmed HNSCC (oral cavity, oropharynx, hypopharynx, larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
• Patients not previously treated for recurrent/metastatic disease.
• Radiographically measurable disease as defined by RECIST version 1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression according to RECIST version 1.1.
• Patients unable for cisplatin-based chemotherapy, defined "unable" by:
• Karnofsky 70% or
• Karnofsky 80-100% and amenable to chemotherapy, but:
• i. Impaired renal function, creatinine clearance \>30 mL/min and \<80 mL/min GFR could be assessed by direct measurement (EDTA or creatinine clearance) if available or by calculation from serum or plasma creatinine (see annex 5), or
• ii. grade ≥2 hearing loss, according to the NCI CTCAE v 5.0, or
• iii. Class III heart failure according to the New York Heart Association (annex 9), or
• iv. History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds or
• v. Prior dose of cisplatin ≥225 mg/m² for locally advanced disease (a patient who received prior RT + 3 cycles of cisplatin 100 mg/m2 or 3 cycles induction TPF (with cisplatin ≥75/m2) for locally advanced primary HN cancer can be included), or
• vi. Disease progression or relapse during or within 6 months of receiving platinum-based therapy administered as neoadjuvant, adjuvant therapy or as concomitant chemotherapy with radiotherapy and have received at least 200 mg/m2 of cisplatin.
• Male or female patients aged ≥18 years. Patients aged ≥70 years old can only be included with a G8 (Geriatric 8) health status screening score ≥ 14.
• Clinical laboratory values as specified below within 28 days before the first dose of study drug:

You may not qualify if:

• Male or female patients aged \<18 years. Patients aged ≥ 70 years old should not be included with a G8 (Geriatric 8) health status screening score \< 14.
• Karnofsky \<70%.
• Patients that meets more than one of the following criteria:
• Karnofsky 70%,
• Impaired renal function, creatinine clearance \>30 mL/min and \<80 mL/min GFR could be assessed by direct measurement (EDTA or creatinine clearance) if available or by calculation from serum or plasma creatinine (see annex 5),
• Class III heart failure according to the New York Heart Association (annex 9).
• Histologically confirmed recurrent or metastatic squamous cell carcinoma of unknown primary, of the nasopharynx or non-squamous histologies (eg, mucosal melanoma).
• Active brain metastases or leptomeningeal metastases.
• Carcinomatous meningitis.
• Active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
• Diagnosis of immunodeficiency or any condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
• History of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function.
• Prior therapy with experimental antitumor vaccines; any T-cell co-stimulation agents or inhibitors of checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody; or other agents specifically targeting T cells are prohibited.
• Any serious medical or psychiatric illness, including drug or alcohol abuse, that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

Sponsors & Collaborators

• Grupo Español de Tratamiento de Tumores de Cabeza y Cuello: lead
• Bristol-Myers Squibb: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (21)

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Donostia- Donostia Unibertsitate Ospitalea

San Sebastián, San Sebastían, 20014, Spain

Location

Centro Oncoloxico de Galicia

A Coruña, 15009, Spain

Location

Hospital Universitari Germans Trias i Pujol de Badalona

Badalona, 08916, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Institut Català D´Oncologia- Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Universitari de Girona Dr. Josep

Girona, 17007, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Regional de Málaga

Málaga, 29010, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

Complejo Asistencial Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Virgen de la Salud

Toledo, 45004, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario y Politécnico la Fe

Valencia, 46026, Spain

Location

Hospital Clínico Universitario Lozano

Zaragoza, 50009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

Nivolumab; Paclitaxel; Cetuximab

Condition Hierarchy (Ancestors)

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

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

Results Point of Contact

• Title: Juan Luis Sanz (MW)
• Organization: APICES

juanluis.sanz@apices.es

+34 918166804

Study Officials

• Ricard Mesia, MD

  Hospital Universitari Germans Trias i Pujol de Badalona

  PRINCIPAL INVESTIGATOR

• Lara Iglesias, MD

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: February 24, 2020
• Study Start: June 3, 2020
• Primary Completion: September 1, 2023
• Study Completion: March 21, 2024
• Last Updated: June 26, 2025
• Results First Posted: June 26, 2025

Record last verified: 2025-06

Locations

ES (21)