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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03838263
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
UNICANCER

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

Condition or disease Intervention/treatment Phase
Oropharynx Cancer Drug: Nivolumab Radiation: Chemoradiation Phase 2

Detailed Description:

Methodology:

Patient screened wil be randomized 2:1 between 2 arms:

  • Experimental arm: Nivolumab 2 infusions (2 weeks part) before standard of care chemoradiation for 7 weeks with cisplatin at week 1, 4, and 7
  • Control arm: Standard of care chemoradiation for 7 weeks with cisplatin at week 1, 4, and 7

Primary Objective:

To assess the feasibility and tolerance of neoadjuvant nivolumab treatment before chemoradiation in "high-risk" HPV-driven Oropharynx Cancer

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Open Label, Phase II Study Evaluating the Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer
Actual Study Start Date : July 25, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental arm
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
2 nivolumab infusion (240 mg IV) 2 weeks apart (on day 1 and day 15) followed by standard chemoradiation.
Other Name: ANY

Radiation: Chemoradiation
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
Other Name: Radiation + cisplatin

Active Comparator: Control arm
Control arm: Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7
Radiation: Chemoradiation
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
Other Name: Radiation + cisplatin




Primary Outcome Measures :
  1. The rate of patients that fulfill the 3 or 5 conditions as described below (Feasibility assessment of nivolumab neoadjuvant treatment before chemoradiation) [ Time Frame: Between baseline and until 3 months (at the end of 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



Secondary Outcome Measures :
  1. The incidence of Adverse Events related or not related to chemoradiation and Nivolumab [ Time Frame: During treatment phase and until 90 days after the last fraction of radiotherapy ]
    Acute and delayed toxicities assessed according to national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0

  2. Objective Response Rate in the experimental arm [ Time Frame: Between baseline and up to 17 days after the second infusion of nivolumab ]
    Radiological response will be assessed according to RECIST 1.1.

  3. Tumor Response in both arms [ Time Frame: Between baseline and 3 months after the end of chemoradiation ]
    Radiological response will be assessed according to RECIST 1.1.

  4. Overall Survival (OS) [ Time Frame: Between baseline and 2 years after the end of chemoradiation ]
    the time from randomization to death from any cause

  5. Locoregional control (LRC) [ Time Frame: Between baseline and 2 years after the end of chemoradiation ]
    the absence of disease progression (radiological progression according to RECIST 1.1 or clinical progression) or recurrence at the site of the primary tumor and loco-regional lymph nodes.

  6. Progression-Free Survival (PFS) [ Time Frame: Between baseline and 2 years after the end of chemoradiation ]
    The time from randomization to progression or death from any cause

  7. Objective Response Rate in the experimental arm [ Time Frame: Between baseline and up to 17 days after the second infusion of nivolumab ]
    Standardized uptake value (SUV) evolution will be assessed by positron emission tomography (PET)-scan.

  8. Tumor Response in both arms [ Time Frame: Between baseline and 3 months after the end of chemoradiation ]
    SUV evolution will be assessed by PET-scan.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years old
  2. 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)
  3. 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)
  4. Planned date of chemoradiation allowing 2 treatment infusions, 2 weeks apart
  5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  6. Screening laboratory values must meet the following criteria (using CTCAE v5.0) and should be obtained within 7 days prior to the randomisation:

    1. Polynuclear neutrophils ≥1.5 x 10⁹/L
    2. Platelets ≥100 x 10⁹/L
    3. Hemoglobin ≥9.0 g/dL
    4. Alanine aminotransferase (ALAT)/aspartate transaminase (ASAT) ≤2.5 x upper limit of normal (ULN)
    5. Total Bilirubin ≤1.5 x ULN (except Gilbert Syndrome : <3.0 mg/dL)
    6. Creatinine clearance ≥60 mL/min (measured or calculated by Cockcroft and Gault formula)
  7. 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
  8. Women of childbearing potential must have a negative serum or urine pregnancy test done within 72 hours before randomisation
  9. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures (including mandatory study-specific biopsies)
  10. Subjects must have at least one lesion amenable to biopsy
  11. Subjects must have at least one measurable lesion (different from the lesion amenable to biopsy) as per RECIST 1.1 criteria to assess efficacy
  12. Consent to provide archived tumour tissue sample, if available
  13. Patients must be affiliated to a Social Security System
  14. Patient information and written informed consent form signed

Exclusion Criteria:

  1. Prior treatment for OPSCC
  2. Prior treatment with anti PD-1/PD-L1 and CTLA-4
  3. Distant metastases
  4. Tumour embolization within 28 days prior to the first dose of study drug.
  5. 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)
  6. 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
  7. Current or prior use of immunosuppressive medication within 14 days before the first dose, including intranasal and inhaled corticosteroids or systemic corticosteroids
  8. 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)
  9. History of primary immunodeficiency or organ transplant requiring immunosuppressive drugs
  10. Patients with a known HIV, active hepatitis B or C infection
  11. 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
  12. Pregnant women or women who are breast-feeding
  13. 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
  14. Individuals deprived of liberty or placed under the authority of a tutor
  15. Severe infection requiring parenteral antibiotics treatment
  16. Known history or active symptomatic interstitial lung disease
  17. Patients with major surgery within 28 days, or open biopsy within 7 days, prior to randomisation. Patients must have recovered from major side effects of the surgery before randomisation

Information from the National Library of Medicine

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): NCT03838263


Contacts
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Contact: Jessy DELAYE, MSc (0)144235577 ext +33 j-delaye@unicancer.fr

Locations
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France
Hopital Beaujon Not yet recruiting
Clichy, France, 92100
Contact: Michele LAMURAGLIA, MD    33 1 40 87 45 87    michele.lamuraglia@aphp.fr   
Centre Léon Bérard Not yet recruiting
Lyon, France, 69373
Contact: Jerome FAYETTE, MD    33 4 78 78 51 03    jerome.fayette@lyon.unicancer.fr   
Centre Antoine Lacassagne Not yet recruiting
Nice, France, 06189
Contact: Alexandre BOZEC, MD    33 4 92 03 17 47    alexandre.bozec@nice.unicancer.fr   
Institut Curie Not yet recruiting
Paris, France, 75005
Contact: Christophe LETOURNEAU, MD    33 1 44 32 46 75    christophe.letourneau@curie.fr   
Hopital Europeen Georges Pompidou Recruiting
Paris, France, 75015
Contact: Haïtman MIRGHANI, MD, PhD    33 1 56 09 34 40    haitman.mirghani@aphp.fr   
Hopital Tenon Not yet recruiting
Paris, France, 75970
Contact: Florence HUGUET, MD    33 1 56 01 83 22    florence.huguet@aphp.fr   
Centre Henri Becquerel Not yet recruiting
Rouen, France, 76038
Contact: Florian CLATOT, MD    33 2 32 08 29 81    florian.clatot@chb.unicancer.fr   
Hopital Foch Not yet recruiting
Suresnes, France, 92150
Contact: Stephane HANS, MD    33 1 46 25 31 21    s.hans@hopital-foch.org   
Institut de cancerologie de Lorraine Alexis Vautrin Not yet recruiting
Vandoeuvre-Les-Nancy, France, 54519
Contact: Lionel GEOFFROIS, MD    33 3 83 59 84 61    l.geoffrois@nancy.unicancer.fr   
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Pierre BLANCHARD, MD    33 1 42 11 65 32    pierre.blanchard@gustaveroussy.fr   
Sponsors and Collaborators
UNICANCER
Investigators
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Principal Investigator: Haïtham MIRGHANI, MD, PhD HOPITAL EUROPEEN GEORGES POMPIDOU

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Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT03838263    
Other Study ID Numbers: UC-0130/1804
2018-000626-60 ( EudraCT Number )
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNICANCER:
Nivolumab
High-risk
HPV-driven oropharynx cancer
Additional relevant MeSH terms:
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Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Nivolumab
Antineoplastic Agents
Antineoplastic Agents, Immunological