Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer

NCT03838263 | Completed Phase 2 DMC

• 2 other identifiers: UC-0130/18042018-000626-60
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 11

Brief Summary

The aim of this research is to study the feasibility of neoadjuvant treatment before chemoradiation in "high risk" HPV-driven Oropharynx cancer

Conditions

Oropharynx Cancer

Keywords

Nivolumab; High-risk; HPV-driven oropharynx cancer

Outcome Measures

Primary Outcomes (1)

• The rate of patients that fulfill the 3 or 5 conditions as described below (Feasibility assessment of nivolumab neoadjuvant treatment before chemoradiation)

  the rate of patients : (1) who can receive the 2 nivolumab infusions planned at D1 and between D14 to D16 among patients in the experimental arm And (2) who can receive chemoradiation at D30 (-2 /+7) after the second nivolumab infusion, without delay of more than 7 days with respect to the planned start of chemoradiation (RT-CT) among patients in the experimental arm And (3) with no radiotherapy break of one week or more, among patients in the experimental arm and patients in the control arm separately And (4) with minimal dose of radiotherapy (dose received \>95% of theoretical dose) among patients in the experimental arm and patients in the control arm separately And (5) with minimal dose of chemotherapy of ≥200 mg/m² of cisplatin (CDDP) among patients in the experimental arm and patients in the control arm separately

  Between baseline and until 3 months (at the end of chemoradiation)

Secondary Outcomes (8)

• The incidence of Adverse Events related or not related to chemoradiation and Nivolumab

  During treatment phase and until 90 days after the last fraction of radiotherapy

• Objective Response Rate in the experimental arm

  Between baseline and up to 17 days after the second infusion of nivolumab

• Tumor Response in both arms

  Between baseline and 3 months after the end of chemoradiation

• Overall Survival (OS)

  Between baseline and 2 years after the end of chemoradiation

• Locoregional control (LRC)

  Between baseline and 2 years after the end of chemoradiation

Study Arms (2)

Experimental arm

EXPERIMENTAL

Experimental arm with nivolumab 2 infusions (2 weeks apart) before Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7

Drug: Nivolumab; Radiation: Chemoradiation

Control arm

ACTIVE COMPARATOR

Control arm: Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7

Radiation: Chemoradiation

Interventions

Nivolumab DRUG

2 nivolumab infusion (240 mg IV) 2 weeks apart (on day 1 and day 15) followed by standard chemoradiation.

Also known as: ANY

Experimental arm

Chemoradiation RADIATION

Standard of Care chemoradiation for 7 weeks (70 Gray delivered to the tumor by IMRT) with high-dose cisplatin (100mg/m2) at week 1, 4 and 7

Also known as: Radiation + cisplatin

Control arm; Experimental arm

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years old
• Histologically confirmed HPV-positive Oropharyngeal squamous cell carcinoma (OPSCC) amenable to curative treatment with RT-CT (HPV status is defined on the basis of the combination of 2 assays: p16 protein overexpression assessed by immunohistochemistry (IHC) and high-risk HPV DNA identification by in-situ Hybridization (ISH) or PCR. An HPV-driven OPSCC is defined as a tumor that is positive for both p16 IHC and HPV-DNA ISH or PCR)
• According to the 8th TNM edition, eligible stages are as follow:
• Irrespective of tobacco consumption: Stage T4 (any N), N2 or N3 (any T)
• Only if tobacco consumption ≥10 pack- years: T1-3N1 and T3N0 (T1N0 and T2N0 irrespective of tobacco consumption are not eligible for the study)
• Planned date of chemoradiation allowing 2 treatment infusions, 2 weeks apart
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Screening laboratory values must meet the following criteria (using CTCAE v5.0) and should be obtained within 7 days prior to the randomisation:
• Polynuclear neutrophils ≥1.5 x 10⁹/L
• Platelets ≥100 x 10⁹/L
• Hemoglobin ≥9.0 g/dL
• Alanine aminotransferase (ALAT)/aspartate transaminase (ASAT) ≤2.5 x upper limit of normal (ULN)
• Total Bilirubin ≤1.5 x ULN (except Gilbert Syndrome : \<3.0 mg/dL)
• Creatinine clearance ≥60 mL/min (measured or calculated by Cockcroft and Gault formula)
• Potentially reproductive patients must agree to use a highly effective contraceptive method while on treatment and up to 6 months after the end of chemoradiation

You may not qualify if:

• Prior treatment for OPSCC
• Prior treatment with anti PD-1/PD-L1 and CTLA-4
• Distant metastases
• Tumour embolization within 28 days prior to the first dose of study drug.
• Contra-indication(s) to receive high-dose cisplatin as listed in the most updated Summary of Product Characteristics (including creatinine clearance \<60 mL/min, pre-existing hearing loss or neurological disorder)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness and social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent
• Current or prior use of immunosuppressive medication within 14 days before the first dose, including intranasal and inhaled corticosteroids or systemic corticosteroids
• Active or prior documented autoimmune or inflammatory disease within the 2 years prior to start of treatment (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\], celiac disease, irritable bowel disease, or other serious chronic gastrointestinal conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome \[granulomatosis with polyangiitis\]; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis, etc.) The following are exceptions to these criteria:a) Subjects with vitiligo or alopecia, b) Subjects with hypothyroidism (e.g.,Hashimoto syndrome) stable on hormone replacement and c) Subjects with psoriasis not requiring systemic treatment (within the past 2 years)
• History of primary immunodeficiency or organ transplant requiring immunosuppressive drugs
• Patients with a known HIV, active hepatitis B or C infection
• Other invasive malignancy within 3 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
• Pregnant women or women who are breast-feeding
• Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the study
• Individuals deprived of liberty or placed under the authority of a tutor
• Severe infection requiring parenteral antibiotics treatment

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (11)

Institut Sainte Catherine

Avignon, 84918, France

Location

Hopital Beaujon

Clichy, 92100, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

Hopital Tenon

Paris, 75970, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Hopital Foch

Suresnes, 92150, France

Location

Institut de cancerologie de Lorraine Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Nivolumab; Chemoradiotherapy; Radiation; Cisplatin

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Physical Phenomena; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Haïtham MIRGHANI, MD, PhD

  HOPITAL EUROPEEN GEORGES POMPIDOU

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: In this study, there are 2 arms: * Experimental arm with nivolumab 2 infusions (2 weeks apart) before Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7 * Control arm: Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 12, 2019
• Study Start: July 25, 2019
• Primary Completion: April 1, 2022
• Study Completion: November 20, 2024
• Last Updated: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

Locations

FR (11)