Phase II Multicenter Randomized Trial to Assess the Efficacy and Safety of First Line Nivolumab in Combination With Paclitaxel in Subjects With R/M HNSCC Unable for Cisplatin-based Chemotherapy (NIVOTAX)
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab + Paclitaxel
- Conditions
- Not specified
- Sponsor
- Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
- Enrollment
- 141
- Locations
- 21
- Primary Endpoint
- Two Years Overall Survival (OS)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Previously irradiated lesions can only be considered as measurable disease if disease progression according to RECIST version 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
Exclusion Criteria
- •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 \<
- •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).
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy except for alopecia, vitiligo, hear loss and the laboratory values defined in the inclusion criteria.
- •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.
Arms & Interventions
Arm 1
NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab)
Intervention: Nivolumab + Paclitaxel
Arm 2
ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab)
Intervention: Cetuximab + Paclitaxel
Outcomes
Primary Outcomes
Two Years Overall Survival (OS)
Time Frame: 2 years
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.
Secondary Outcomes
- Progression Free Survival Based on Cisplatin Ineligibility.(Up to 45 months)
- 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)
- Overall Survival in Patients ≥ 70 Years.(Up to 45 months)
- Progression Free Survival in Patients ≥ 70 Years.(Up to 45 months)
- Overall Response Rate in Patients ≥ 70 Years.(Up to 2 years)
- Overall Survival Based on PDL1 Expression (CPS).(Up to 45 months)
- Progression Free Survival Based on PDL1 Expression (CPS).(Up to 45 months)
- Overall Response Rate Based on PDL1 Expression (CPS).(Up to 2 years)
- Overall Survival Based on Cisplatin Ineligibility.(Up to 45 months)
- Overall Response Rate Based on Cisplatin Ineligibility.(Up to 2 years)
- Overall Survival Based on Karnofsky.(Up to 45 months)
- Progression Free Survival Based on Karnofsky.(Up to 45 months)
- Overall Response Rate Based on Karnofsky.(Up to 2 years)
- Percentage of Patients With AEs(2 years)
- Percentage of Patients With Grade 3 and Grade 4 AEs(2 years)
- Percentage of Patients With SAEs(Up to 45 months)
- Percentage of Patients Who Discontinued Due to AEs(Up to 2 years)