Nivolumab in Recurrent and/or Metastatic SCCHN (TopNIVO)
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|ClinicalTrials.gov Identifier: NCT03226756|
Recruitment Status : Active, not recruiting
First Posted : July 24, 2017
Last Update Posted : April 17, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent and/or Metastatic Platinum-refractory SCCHN||Drug: Nivolumab Injection||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||351 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Safety Study of Nivolumab in Patients With Recurrent and/or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)|
|Actual Study Start Date :||August 7, 2017|
|Actual Primary Completion Date :||December 31, 2017|
|Estimated Study Completion Date :||March 2021|
All patients enrolled in the study will received Nivolumab injections, 3mg/kg IV, every 2 weeks, up to 12 cycles (1 cycle = 28 days).
Drug: Nivolumab Injection
Nivolumab 3 mg/kg, every 2 weeks
- 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) [ Time Frame: 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.
- Time to onset of grade 3+ AEI [ Time Frame: 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.
- Time to resolution of grade 3-4 AEI to grade 1 [ Time Frame: 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 at least one or more doses of nivolumab delayed (or cancelled) due to AE [ Time Frame: Up to 24 months of treatment ]The rate of patients with one or more doses of nivolumab cancelled due to AE will be estimated.
- Rate of patients with nivolumab definitely withdrawn due to AE [ Time Frame: Up to 24 months of treatment ]The rate of patients with nivolumab definitively withdrawn due to AEs will be estimated.
- Rate of Nivolumab-related deaths [ Time Frame: 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 [ Time Frame: 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.
- Duration of all immune modulating medications given for the select event and summary of patients with resolution of AEs after initiating these therapies. [ Time Frame: 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 AEI of maximum grade 1-2 [ Time Frame: 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) [ Time Frame: 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.
- Progression free survival (PFS) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03226756
|Principal Investigator:||Caroline Even, MD||Gustave Roussy Cancer Campus - Villejuif|