Biomarker-based Study in R/M SCCHN

NCT03088059 | Unknown Phase 2 DMC

• 2 other identifiers: EORTC-1559-HNCG2017-000086-74
• Study Type: interventional
• Target: 340
• Locations: 5 countries
• Sites: 36

Brief Summary

This is a biomarker-driven trial that will enroll patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing after first-line platinum-based chemotherapy. Based on potential biomarkers and molecular alterations identified in the biopsy from the central platform, patients will be allocated in different cohorts. There will be biomarker-positive patient cohorts and immunotherapy cohorts.

Conditions

Carcinoma, Squamous Cell of Head and Neck

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival Rate (PFSR) at week 16

  Progression Free Survival Rate (PFSR) at week 16 will be assessed as primary endpoint for all patients from cohorts 1, 2 and 3.

  The Progression Free Survival Rate (PFSR) analysis will be performed at week 16 for each patient in cohorts 1, 2 and 3.

• Objective response Rate (ORR) at week 16

  Objective response Rate (ORR) during the first 16 weeks of study treatment will be assessed as primary endpoint for all patients from cohort 4-8.

  Objective response Rate (ORR) at week 16 will be performed at week 16 for each patient in cohort 4.

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  54 months after first patient in

• Objective Response Rate

  48 months after first patient in

• Response duration

  54 months after first patient in

• Overall Survival (OS)

  54 months after first patient in

• Toxicity according CTCAE version 4.03

  54 months after first patient in

Study Arms (8)

Patient Cohort B1

EXPERIMENTAL

Patients who are p16 negative and have an EGFR amplification/mutation or PTEN high or HER2 mutation/amplification will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care).

Drug: Afatinib; Drug: standard of care

Patient Cohort B2

EXPERIMENTAL

Patients who are p16 negative and cetuximab naïve will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)

Drug: Afatinib; Drug: standard of care

Patient Cohort B3

EXPERIMENTAL

Patients who are p16 negative and have an amplification of CCND1 will be randomized between palbociclib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)

Drug: Palbociclib; Drug: standard of care

Patient Cohort B4

EXPERIMENTAL

Patients who are p16 negative and 'platinum sensitive' SCCHN will receive niraparib

Drug: Niraparib

Patient Cohort B5

EXPERIMENTAL

Patients whith oropharyngeal cancer and which are p16 positive will receive niraparib

Drug: Niraparib

Patient Cohort I1

EXPERIMENTAL

Patients who are anti-PD(L)1-naïeve or resistant (primary or secondary resistance) will receive IPH2201 antibody (monalizumab).

Drug: IPH2201

Patient Cohort I2

EXPERIMENTAL

Patient who are PD(L)1 pretreated will be randomized between monalizumab + durvalumab or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)

Drug: standard of care; Drug: IPH2201; Drug: Durvalumab

Patient Cohort I3

EXPERIMENTAL

Patient who are progressing prior PD(L)1 after having received at least 2 months of anti-PD(L)-1 will receive INCAGN01876.

Drug: INCAGN01876

Interventions

Afatinib DRUG

Afatinib 40 mg given orally, once daily, 1 cycle is 28 days

Patient Cohort B1; Patient Cohort B2

Palbociclib DRUG

Palbociclib 125 mg given orally, once daily, 1 cycle is 28 days (21 days on treatment, then 7 days off)

Patient Cohort B3

standard of care DRUG

Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care

Patient Cohort B1; Patient Cohort B2; Patient Cohort B3; Patient Cohort I2

IPH2201 DRUG

protocol v2.0 and 2.1 : Monalizumab 10mg/kg given intravenously over 60 minutes, once every 14 days, 1 cycle is 14 days protocol v4.0 : Monalizumab 750mg given intravenously over 60 minutes, once every 28 days, 1 cycle is 28 days

Also known as: Monalizumab

Patient Cohort I1; Patient Cohort I2

Durvalumab DRUG

Durvalumab 1500mg given intravenously over 60 minutes, once every 28 days, 1 cycle is 28 days

Patient Cohort I2

Niraparib DRUG

Niraparib 300 mg given orally, once daily, 1 cycle is 28 days

Patient Cohort B4; Patient Cohort B5

INCAGN01876 DRUG

INCAGN01876 300 mg given intravenously over 30 minutes, once every 14 days, 1 cycle is 28 days

Patient Cohort I3

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed recurrent and/or metastatic SCCHN of the oral cavity, oropharynx, hypopharynx or larynx not amenable to curative treatment.
• At least one measurable lesion by MRI or CT-scan according to RECIST 1.1, evaluated within 2 weeks prior to registration. Such lesion must not have been previously irradiated; if the measurable lesion(s) have been irradiated, clear progression must be documented.
• Progressive disease after first line platinum-based chemotherapy with or without cetuximab given as palliative treatment or progressive disease within 1 year if platinum-based chemotherapy was given as a part of the multimodal curative treatment. Patients pre-treated with anti-PD1/anti-PDL1 are allowed.
• ECOG performance status 0 -1 with a life expectancy of at least 12 weeks.
• Tumor core biopsy from any accessible tumor at the recurrent or metastatic site available for central testing.
• Patients must have adequate organ function, evaluated within 14 days prior to cohort allocation:
• Hemoglobin ≥ 9 g/100 ml,
• Neutrophils ≥ 1,500/mm3,
• Platelets ≥ 100,000/mm3,
• Total bilirubin \<1.5 times the upper limit of normal (ULN) (\< 3 times the upper limit of normal for Gilbert's disease),
• Serum ALT and AST ≤ 2.5 x ULN,
• Adequate renal function measured by:
• Estimated creatinine clearance ≥45ml using Cockcroft and Gault formula or Creatinine ≤ 1.5 ULN
• International Normalized Ratio (INR) or Prothrombin Time (PT) must be within the normal ranges as per institution's standard. A window of 5% is allowed.
• Patients receiving anticoagulant therapy are allowed to participate as long as the PT/INR values are within the expected target range of their current dose.

You may not qualify if:

• Unresolved and significant toxicity CTCAE version 4.03 grade ≥ 2 from previous anticancer therapy other than alopecia.
• History of any of the following cardiovascular conditions within 6 months prior to registration:
• myocardial infarction,
• severe/unstable angina,
• ongoing cardiac dysrhythmias of CTCAE version 4.03 Grade 2 or more,
• atrial fibrillation of any grade,
• coronary/peripheral artery bypass graft,
• symptomatic congestive heart failure according to New York Heart Association (NYHA) Class III or Class IV,
• significant active cardiac disease including uncontrolled high blood pressure defined as systolic ≥150 and diastolic ≥100.
• cerebrovascular accident including transient ischemic attack
• thromboembolic events like symptomatic pulmonary embolism.
• Nasopharynx and sino-nasal tumor.
• Surgery or investigational drugs or chemotherapy or other anticancer therapy within 3 weeks before cohort allocationor or for investigational drugs, within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter. Participant must have recovered from any surgical procedure. Curative radiation therapy (60-70 Gy) within 6 weeks of cohort allocation. Palliative radiation therapy (e.g. 8 Gy on a painful lesion) will be allowed.
• Known untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis.
• Known diagnosis of immune deficiency or a positive serology of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (36)

CHU Saint-Pierre-Site Porte de Hal

Brussels, 1000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, Belgium

Location

Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame

Charleroi, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

Hopital De Jolimont

Haine-Saint-Paul, Belgium

Location

AZ Groeninge Kortrijk - Campus Kennedylaan

Kortrijk, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, Belgium

Location

GasthuisZusters Antwerpen - Sint-Augustinus

Wilrijk, Belgium

Location

CHU Dinant Godinne - UCL Namur

Yvoir, Belgium

Location

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre

Bordeaux, France

Location

Centre Georges-Francois-Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Curie

Paris, France

Location

Institut de Cancerologie Strasbourg Europe

Strasbourg, 67200, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, France

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

IRCCS - Fondazione G. Pascale

Napoli, 80131, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Napoli, Italy

Location

ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)

Barcelona, 08908, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

Location

University Hospitals Birmingham NHS Foundation Trust (UHB) - UHB-Queen Elisabeth Medical Centre

Birmingham, United Kingdom

Location

NHS Lothian - Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

NHS Lothian - Western General Hospital

Edinburgh, United Kingdom

Location

NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital

Glasgow, United Kingdom

Location

Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital

London, United Kingdom

Location

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital

Sheffield, United Kingdom

Location

Related Publications (1)

• Galot R, Le Tourneau C, Guigay J, Licitra L, Tinhofer I, Kong A, Caballero C, Fortpied C, Bogaerts J, Govaerts AS, Staelens D, Raveloarivahy T, Rodegher L, Laes JF, Saada-Bouzid E, Machiels JP. Personalized biomarker-based treatment strategy for patients with squamous cell carcinoma of the head and neck: EORTC position and approach. Ann Oncol. 2018 Dec 1;29(12):2313-2327. doi: 10.1093/annonc/mdy452.

  PMID: 30307465 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Afatinib; palbociclib; Standard of Care; monalizumab; durvalumab; niraparib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

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

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: March 23, 2017
• Study Start: November 16, 2017
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 3, 2023

Record last verified: 2023-11

Locations

BE (12); ES (3); GB (7); IT (5); FR (9)