Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
Trial record 1 of 1 for:    adjorl
Previous Study | Return to List | Next Study

Immunotherapy in Head and Neck Squamous Cell Carcinoma : Phase 2 Trial Evaluating the Efficacy and the Toxicity of Nivolumab Alone, and of the Combination Nivolumab and Ipilimumab (ADJORL1)

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: NCT03406247
Recruitment Status : Not yet recruiting
First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris

Brief Summary:
Two randomized trials of reirradiation after salvage surgery have been conducted by the GETTEC and GORTEC collaborative groups, both members of the French HN Intergroup: The first trial compared reirradiation and a "wait and see attitude" and was published in 2008 [1]. The second trial compared two modalities of reirradiation. Our hypothesis is that adjuvant treatment with immunotherapy will lead to a DFS similar to that observed in previous trials of post-operative reirradiation with possibly lower toxicity.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: Nivolumab Drug: Ipilimumab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Immunotherapy After Salvage Surgery in Head and Neck Squamous Cell Carcinoma : Phase 2 Trial Evaluating the Efficacy and the Toxicity of Nivolumab Alone, and of the Combination Nivolumab and Ipilimumab
Estimated Study Start Date : February 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nivolumab
Patients in cohorts 1 and 1bis will be administered Nivolumab 240 mg every 2 weeks during 3 first months and then 480 mg every 4 weeks during 3 months
Drug: Nivolumab

Patients in cohorts 1 and 1bis will be administered Nivolumab 240 mg every 2 weeks during 3 first months and then 480 mg every 4 weeks during 3 months Patients in cohorts 2 and 2bis will be administered

- nivolumab 240 mg every 2 weeks during 6 months


Experimental: Nivolumab + Ipilimumab

Patients in cohorts 2 and 2bis will be administered

  • nivolumab 240 mg every 2 weeks during 6 months
  • ipilimumab 1mg/kg IV every 6 weeks during 6 months
Drug: Nivolumab

Patients in cohorts 1 and 1bis will be administered Nivolumab 240 mg every 2 weeks during 3 first months and then 480 mg every 4 weeks during 3 months Patients in cohorts 2 and 2bis will be administered

- nivolumab 240 mg every 2 weeks during 6 months


Drug: Ipilimumab

Patients in cohorts 2 and 2bis will be administered

- ipilimumab 1mg/kg IV every 6 weeks during 6 months





Primary Outcome Measures :
  1. Two Years Disease Free Survival [ Time Frame: Two years ]
    defined as the time from the beginning of the immunotherapy and the first locoregional or distant recurrence, or death from any cause, in cohorts 1 and 2



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Recurrence or second primary of HNSCC in a previously irradiated area at a dose ≥ 50 Gys
  • HNSCC of oral cavity, oro and hypopharynx, larynx only if extralaryngeal spread (rT4), isolated nodal recurrence
  • Patient who has received salvage surgery with curative intent and macroscopic complete resection:
  • for cohorts 1 and 2: similarly to inclusion criteria of previous reirradiation trials, more than 6 months between radiotherapy and salvage surgery
  • for cohorts 1bis and 2bis: less than 6 months between radiotherapy and salvage surgery
  • Recurrence of bad prognosis justifying an adjuvant treatment:
  • clinically infiltrative recurrence or second primary; or nodal recurrence upper or equal to 3 cm, or association of local and nodal recurrence;
  • superficial recurrence, but histologic gravity signs on surgical specimen indicating a high risk of recurrence after salvage surgery (histologic involvement of surgical margins or margins less than 3mm, perineural spread or vascular emboli, multiples invaded nodes). Nodal recurrence without tumor recurrence and inferior to 3cm, but with capsular rupture at histologic examination.
  • Sufficient healing for beginning adjuvant treatment within 8 weeks (+/- 2 weeks) of salvage surgery
  • No distant metastases, confirmed by CT or PET scan
  • Male and female between 18 and 75 years (included)
  • ECOG 0 or 1
  • 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
  • Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 14 days to the administration of the first study treatment.: WBC > 2000/μL. Polynuclear neutrophils >1.5 x 109/L. Platelets > 75 x 109/L. Hemoglobin > 8.0 g/dL. ALAT/ASAT< 3.0 x ULN. Bilirubin < 1.5 x ULN (except Gilbert Syndrome

    : < 3.0 mg/dL). Creatinine clearance > 40 mL/min (measured or calculated by Cockroft and Gault formula) or serum creatinine < 2.0 x ULN

  • Women of childbearing potential must have a negative serum β-HCG pregnancy test within 24 hours prior to the administration of the first study treatment.
  • Sexually active women of childbearing potential must agree to use a highly effective method of contraception or to abstain from sexual activity during the study and for at least 5 months after the last study treatment administration. Sexually active males patients must agree to use condom during the study and for at least 7 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception.
  • Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 5 months after the last dose.
  • Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
  • Patients must be affiliated to a social security system or beneficiary of the same

Exclusion Criteria:

  • Recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma that originated from the skin and salivary gland, or nonsquamous histologies (eg, mucosal melanoma).
  • Recurrence or second primary of HNSCC in a non previously irradiated area, or at a dose < 50 Gys
  • Macroscopic incomplete surgery (no debulking allowed)
  • Superficial recurrence without nodal recurrence, and without histologic gravity signs (histologic involvement of surgical margins, perineural spread)
  • Nodal recurrence less than 3 cm, without local recurrence and without capsular rupture at histologic examination
  • Serious medical adverse conditions, such as severe cardiac and/or pneumologic and/or liver dysfunction. Non exhaustive list, to be appreciated in each center
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur inthe 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.
  • Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
  • Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • 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.
  • Patients having received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • Patients receiving anti-cancer therapies must be discontinued at least 4 weeks prior to administration of study drug. Palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks before administration of study drug. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI CTCAE version 4) or to baseline or stabilized before administration of study drug. Subjects with toxicities attributed to systemic prior anticancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
  • Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to study drug. The use of the inactivated seasonal influenza vaccine (Fluzone®) is allowed.Known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events.
  • Patients requiring concomitant treatment with therapeutic doses of anticoagulants will not be eligible for this clinical trial. Patients treated with low dose of anticoagulants for thrombo-embolic events prophylaxis are allowed.
  • History of auto immune, immune mediated inflammatory disease including but not limited to colitis, pneumonitis, hepatitis, nephritis, inflammatory of skin, SNC, eyes, glands producing hormons
  • Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • History of allergy to study drugs components
  • Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
  • Pregnancy or breastfeeding
  • Psychological, familial or social factor incompatible with informed consent, and regular follow-up.
  • Previous allogenic stem cell transplant or patients recipient of solid organ transplant

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): NCT03406247


Contacts
Layout table for location contacts
Contact: François JANOT, MD 0142114590 ext +33 françois.janot@gustaveroussy.fr
Contact: Federico ROTOLO 0142116128 ext +33 federico.rotolo@gustaveroussy.fr

Locations
Layout table for location information
France
Gustave Roussy
Villejuif, Val De Marne, France, 94805
Contact: François JANOT, MD    0142114590 ext +33    françois.janot@gustaveroussy.fr   
Contact: Federico ROTOLO    0142116128 ext +33    federico.rotolo@gustaveroussy.fr   
Principal Investigator: Frnaçois JANOT, MD         
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
Investigators
Layout table for investigator information
Study Chair: François JANOT, MD Gustave Roussy, Cancer Campus, Grand Paris

Layout table for additonal information
Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT03406247    
Other Study ID Numbers: 2017-001277-17
2017/2536 ( Other Identifier: CSET Number )
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: January 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents