Nivolumab in Recurrent and/or Metastatic SCCHN

NCT03226756 | Completed Phase 2 DMC

• 2 other identifiers: UC-0130/17032017-000424-10
• Study Type: interventional
• Target: 351
• Locations: 1 country
• Sites: 18

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.

Conditions

Recurrent and/or Metastatic Platinum-refractory SCCHN

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  Last dose + 100 days

Secondary Outcomes (12)

• Time to onset of grade 3+ AEI

  last dose + 100 days

• 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.

• Rate of patients with at least one or more doses of nivolumab delayed (or cancelled) due to AE

  Up to 24 months of treatment

• Rate of patients with nivolumab definitely withdrawn due to AE

  Up to 24 months of treatment

• Rate of Nivolumab-related deaths

  Up to 36 months.

Study Arms (1)

Nivolumab

EXPERIMENTAL

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

Interventions

Nivolumab Injection DRUG

Nivolumab 3 mg/kg, every 2 weeks

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men and women ≥18 years.
• Histologically confirmed recurrent and/or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of tumor for SCC of the oropharynx.
• Tumor progression or recurrence after a platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting. In the adjuvant or primary setting, the recurrence must have occurred within 6 months after the last dose of platinum therapy. Clinical progression after platinum therapy is an allowable event for entry and is defined as progression of a lesion at least 10 mm in size that is amenable to caliper measurement (eg superficial skin lesion as per RECIST v1.1) or a lesion that has been visualized and photographically recorded with measurements and shown to have progressed.
• Measurable disease by CT or MRI per RECIST v1.1.
• 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.
• 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.
• Patients with brain metastases will be eligible if they are: asymptomatic, without edema, not on corticosteroids, have been treated and there is no magnetic resonance imaging (except where contraindicated in which CT scan is acceptable) evidence of progression for at least 4 weeks after treatment is complete.
• Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 7 days prior to the first study drug administration :
• White blood cell (WBC) ≥2000/μL.
• Polynuclear neutrophils ≥1.5 x 10⁹/L.
• Platelets ≥75 x 10⁹/L.
• Hemoglobin \>8.0 g/mL.
• Alanine aminotransferase (ALAT)/aspartate transaminase (ASAT) ≤3.0 x upper limit of normal (ULN) in the absence of liver metastases or ≤5 x ULN in the presence of liver metastases.

Sponsors & Collaborators

• UNICANCER: lead
• Bristol-Myers Squibb: collaborator

Study Sites (18)

Institut de Cancérologie de l'Ouest

Angers, France

Location

CHU Bordeaux

Bordeaux, 33075, France

Location

Centre Francois Baclesse

Caen, 14176, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Georges Francois Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, France

Location

ICM Val d'Aurelle

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital Tenon

Paris, 75970, France

Location

Institut Curie

Paris, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

Centre Eugène Marquis

Rennes, France

Location

Institut Curie Saint Cloud

Saint-Cloud, 92210, France

Location

Centre Paul Strauss

Strasbourg, 67000, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Caroline Even, MD

  Gustave Roussy Cancer Campus - Villejuif

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2017
• First Posted: July 24, 2017
• Study Start: July 7, 2017
• Primary Completion: December 31, 2017
• Study Completion: May 31, 2022
• Last Updated: January 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)