A Single-Arm, Open-Label, Multicenter, Phase IIIb Clinical Trial With NIVolumab in Subjects With Recurrent or Metastatic Platinum-refrACTORy Squamous Cell Carcinoma of the Head and Neck (SCCHN) - NIVACTOR Study
Overview
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 124
- Locations
- 22
- Primary Endpoint
- Incidence of high-grade (CTCAE v 4.03 Grade 3 or higher) treatment related AE
Overview
Brief Summary
Subjects will receive treatment with nivolumab monotherapy at 240mg flat dose as a 30 minute IV infusion on Day 1 of a treatment cycle every 2 weeks (14 days) until confirmed progression of disease, unacceptable toxicity, death or withdrawal of consent. This study is designed to better evaluate the safety profile of nivolumab in a large series of patients with Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck. The primary endpoint of this study is the incidence of high-grade (CTCAE v 4.03 Grade 3 or higher), treatment-related, select adverse events.
Detailed Description
This clinical trial has established head and neck squamous cell carcinoma as responsive to immunotherapy and nivolumab as a new potential SOC for these patients. As concern safety, high-grade (CTCAE v4.03 Grade 3 or higher), treatment-related, select adverse events occur with a low frequency in patients with Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with nivolumab monotherapy. Nonetheless, this observation arises from patients treated in clinical trial and selected according to clear inclusion and exclusion criteria. Therefore they may not precisely reflect the clinical practice. Using a single large study is warranted in order to expand the safety database and to improve the knowledge on estimated incidence of uncommon, select, high-grade AEs.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
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);
Arms & Interventions
nivolumab
nivolumab monotherapy at 240mg flat dose as a 30-minute IV infusion on Day 1 of a treatment cycle every 2 weeks (14 days) until confirmed progression of disease, unacceptable toxicity, death or withdrawal of consent
Intervention: Nivolumab 240 MG in 24 ML Injection (Drug)
Outcomes
Primary Outcomes
Incidence of high-grade (CTCAE v 4.03 Grade 3 or higher) treatment related AE
Time Frame: From baseline to 100 days after last study treatment
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 Outcomes
- Incidence of all high-grade (Grades 3-5), select adverse events;(From baseline to 100 days after last study treatment)
- Overall Survival(At study end 2 years from last patient enrolled)
- Objective Response Rate(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 24 moths))