Subjects with Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)” MedDRA version: 21.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: OPDIVO - 10 MG/ML- CONCENTRATO PER SOLUZIONE PER INFUSIONE- USO ENDOVENOSO- FLACONCINO (VETRO)- 10 ML- 1 FLACONCINO
Product Name: nivolumab
Product Code: BMS-936558
Pharmaceutical Form: So
Sponsors
Fondazione GONO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed Written Informed Consent; • Willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study • Males and Females, 18 years of age; • Histologically confirmed recurrent or metastatic SCCHN (oral cavity, pharynx, larynx) not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy), p16 positive SCCHN of unknown primary; • Eastern Cooperative Oncology Group (ECOG) performance status = 2; • Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie, with radiation after surgery), primary (ie, with radiation or prior to it or to surgery as induction chemotherapy), recurrent, or metastatic setting; • Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria; • Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of oropharyngeal cancer • Tumor tissue (archival or fresh biopsy specimen) must be available; • Patients with CNS metastases • Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration; • Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test; • Screening laboratory values must meet protocol criteria • Women must not be breastfeeding. • WOCBP and males subjects must agree to follow instructions for method(s) of contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Patients with untreated, symptomatic CNS metastases are excluded; • Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, p16 negative squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg, mucosal melanoma) are not allowed; • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results; • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways; • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast; • Subjects with active, known or suspected autoimmune disease. Subjects with experienced GVH disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition or previous neck RT only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; • All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum-based therapy, are permitted to enroll. • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Subjects who test positive for HCV antibody but negative for HCV ribonucleic acid are permitted to enroll; • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS); • Any Grade 4 laboratory abnormalities; • History of allergy to study drug components; • History of severe hypersensitivity reaction to any monoclonal antibody; • Prisoners or subjects who are involuntarily incarcerated. • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the incidence of high-grade (CTCAE v 4.03 Grade 3 or higher), treatment-related, select adverse events in patients with Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with nivolumab monotherapy;Secondary Objective: • To determine the incidence and to characterize the outcome (duration of serious adverse events [SAE] treatment, dose of immune-modulating agents [ie, steroids] dose of agents used, time to event onset, and event resolution, and worst grade of event) of all high-grade (CTCAE v4.03 Grade 3 or higher) adverse events; • To assess safety, tolerability in all treated subjects; • To estimate Overall Survival (OS) in all treated subjects; • To estimate Investigator-assessed Objective Response Rate (ORR) and Progression-Free Survival (PFS) in all treated subjects;;Primary end point(s): Incidence of high-grade (CTCAE v 4.03 Grade 3 or higher), treatment-related, select adverse events;;Timepoint(s) of evaluation of this end point: Approximately 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Incidence of all high-grade (Grades 3-5), select adverse events; Median time to onset and median time to resolution (Grades 3-4) of select adverse events (resolution of an AE is a subject experiencing complete resolution or improvement to the baseline grade for the AE);; Overall Survival defined as the time from first dosing date to the date of death. A subject who has not died will be censored at last known date alive;; Safety and tolerability measured by the incidence of all AEs, treatment-related AEs, serious AEs, deaths, laboratory abnormalities, and select AEs such as pulmonary, gastrointestinal, skin, renal, hepatic, pancreatic, neurologic, endocrine, infusionrelated, or hypersensitivity;; Objective Response Rate (ORR) defined as the number of subjects with a Best Overall Response (BOR) of a complete response (CR) or Partial Response (PR) divided by the number of all treated (at least 1 dose of nivolumab) subjects. BOR is defined as the best response designation, recorded between the date of first dose and the date of the initial objectively documented tumor progression by the investigator per RECIST v1.1 or the date of subsequent therapy, whichever occurs first. For subjects without documented progression or subsequent therapy, all available response designations will contribute to the BOR determination;; Investigator-assessed Progression Free Survival (PFS) defined as radiological evidence of progression, significant clinical symptomatic progression, the need to introduce a non-study drug therapy or death from any cause;;Timepoint(s) of evaluation of this end point: apporoximately 6 months; from 1 to 8 months after enrolment; 24m FU; from 1 to 8 months after enrolment; at week 9 and at 6 months after enrolment; at week 9 and at 6 months after enrolment | — |
Countries
Italy
Contacts
Public ContactCRO
Clinical Research Technology Srl
Outcome results
None listed