Nivolumab in Recurrent and/or Metastatic SCCHN
- Conditions
- Recurrent and/or Metastatic Platinum-refractory SCCHN
- Interventions
- Registration Number
- NCT03226756
- Lead Sponsor
- UNICANCER
- Brief Summary
Recurrent and/or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) are a common clinical situation and although this group of patients has very heterogeneous disease characteristics, they share a dismal prognosis with a median survival time around 6-11 months and a relatively poor quality of life.
Immunotherapy approaches have recently demonstrated clinical efficacy in more than twenty cancer types, including melanoma, renal cell carcinoma, non-small cell lung cancer (NSCLC) and SCCHN. Nivolumab demonstrated significant overall survival benefit as treatment for recurrent SCCHN in a randomized phase III Study CA209141 conducted on a cohort of 361 patients (240 in the nivolumab arm and 121 in the standard therapy arm), presenting this condition and whose disease had progressed within 6 months after platinum-based chemotherapy. In this study, treatment with nivolumab resulted in significantly longer survival than treatment with standard therapy with a median overall survival of 7.5 months vs 5.1 months (p=0.01).
The main objective of the study is to provide additional insight into the frequency of high-grade AEs related to nivolumab and their outcome, and thus supplement the growing safety database of nivolumab-treated recurrent and/or metastatic squamous cell carcinoma of the head and neck patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 351
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nivolumab Nivolumab Injection All patients enrolled in the study will received Nivolumab injections, 3mg/kg IV, every 2 weeks, up to 12 cycles (1 cycle = 28 days).
- Primary Outcome Measures
Name Time Method Incidence for high-grade (CTCAE v4.0 Grade 3-4-5) adverse events of interest (AEI). AEI are adverse reactions known to be related to nivolumab (i.e. skin, endocrinopathy, gastrointestinal, hepatic, renal, pulmonary, and hypersensitivity adverse events) Last dose + 100 days The rate (and its 95%CI) of patients who report at least one high-grade (Grade 3-4 and Grade 5) adverse events of interest will be provided.
- Secondary Outcome Measures
Name Time Method Time to onset of grade 3+ AEI last dose + 100 days The time to onset of grade 3+ AEI will be estimated by Kaplan-Meier product-limit method. Time to onset is calculated from first dosing date to the grade 3+ onset date. If a patient never experienced the given grade 3+ AEI, the patient will be censored at the date of last dose + 100 days (or at the last contact date if it occurs before date of last dose + 100 days.
Duration of all immune modulating medications given for the select event and summary of patients with resolution of AEs after initiating these therapies. Last dose + 100 days The total duration of all immune modulating medications given for the event will be presented by mean, standard deviation, median, minimum and maximum.
Rate of patients with at least one or more doses of nivolumab delayed (or cancelled) due to AE Up to 24 months of treatment The rate of patients with one or more doses of nivolumab cancelled due to AE will be estimated.
Time to resolution of grade 3-4 AEI to grade 1 the time from the date of grade 3-4 until the date of grade 1, assessed up to 36 months. Time to resolution of grade 3-4 will be estimated by Kaplan-Meier method among patients who had experienced this type of AEI from the grade 3-4 AEI onset date to date of AEI grade 1. If an AEI is ongoing at the time of analysis, the time to resolution will be censored at the last contact date.
Rate of patients with nivolumab definitely withdrawn due to AE Up to 24 months of treatment The rate of patients with nivolumab definitively withdrawn due to AEs will be estimated.
Rate of AEI of maximum grade 1-2 Last dose + 100 days The rate of patients with AEI of highest grade 1-2 during the observation period will be provided.
Overall survival (OS) Up to 36 months. Overall survival is defined as the time from date of inclusion to date of death due to any cause. Patients last known to be alive will be censored at date of last contact. Overall survival will be estimated by Kaplan Meier method.
Rate of Nivolumab-related deaths Up to 36 months. A monitoring of Nivolumab-related deaths is set-up separately in 2 subgroups of the cohort: among patients with ECOG performance status (PS)of 2 and among patients with ECOG performance status of 0 or 1. The monitoring is the same in the two subgroups. We expect that around half of the patients will have performance status of 2.
In each subgroup, the monitoring of nivolumab-related deaths will start at the occurrence of the second related death in that subgroup.Rate of patients who received immune modulating medication or hormonal replacement therapy Last dose + 100 days Management of high-grade adverse events will be characterized by measuring percentage of patients who received immune modulating medication, \> 10 mg prednisone equivalents, hormonal replacement therapy in all treated patients and in patients who have experience high-grade adverse events of interest.
Progression free survival (PFS) Up to 36 months. Progression-free survival is defined as the time since the inclusion in the trial to the first event among progression and death, whatever the cause of death. Progression is defined according to RECIST 1.1. Patients last known to be alive without progression having occurred before will be censored at date of last contact. Progression free survival will be estimated by Kaplan Meier method.
Objective response rate (ORR) (complete response and partial response according to RECIST 1.1 and to iRECIST) during nivolumab treatment The time between the fist dose of treatment until the best response, assessed up to 36 months. The rate of patients with objective response (complete response or partial response) will be provided. The response is the best response obtained at the evaluations performed during treatment and at the end of treatment. Two evaluations of the response will be done: one according to the RECIST 1.1 criteria and one according the Immune-related Response Criteria (iRECIST).
Pseudo progression The time between the first dose of treatment until the first confirmed progression, assessed up to 36 months. Pseudo-progressions will be described (rate, time of occurrence). Pseudo-progression is defined as a progression according to RECIST 1.1 under treatment (≥ 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non target lesions or new lesion) that is not confirmed, as per iRECIST, at the next evaluation done 4 to 6 weeks later.
Trial Locations
- Locations (18)
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Centre Paul Strauss
🇫🇷Strasbourg, France
Centre Oscar Lambret
🇫🇷Lille, France
Institut Curie Saint Cloud
🇫🇷Saint Cloud, France
Gustave Roussy
🇫🇷Villejuif, France
Hopital Tenon
🇫🇷Paris, France
Institut de Cancérologie de l'Ouest
🇫🇷Angers, France
ICM Val d'Aurelle
🇫🇷Montpellier, France
Centre Eugène Marquis
🇫🇷Rennes, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut Curie
🇫🇷Paris, France
Institut Jean Godinot
🇫🇷Reims, France
CHU Bordeaux
🇫🇷Bordeaux, France
Centre Francois Baclesse
🇫🇷Caen, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Institut de Cancérologie de Lorraine
🇫🇷Vandœuvre-lès-Nancy, France