Clinical trial NCT03088059: Biomarker-based Study in R/M SCCHN
Official title: A Pilot Study of Personalized Biomarker-based Treatment Strategy or Immunotherapy in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Squamous Cell of Head and Neck
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2017-03-23
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: General Inclusion Criteria:

* 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.
* Clinically normal cardiac function based on -left ventricular ejection fraction (≥ 50%) as assessed either by multi-gated acquisition scan or cardiac ultrasound and 12 lead ECG without clinically relevant abnormalities.
* Patients ≥ 18 years old and must be able to give written informed consent.
* Patients ≥ 70 years old must undergo the G8 screening.
* Women of child-bearing potential must have a negative pregnancy test (serum or urine within the 72 hours prior to cohort allocation).
* Patients of childbearing / reproductive potential must agree to use highly effective methods of contraception based on the Clinical Trial Facilitation Group (CTFG) guidance as of registration and up to 6 months after the last treatment dose. Highly effective methods can achieve failure rate of less than 1% per year when used consistently and correctly. Such methods include: For Women: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal and transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner and sexual abstinence. For Men: condoms, sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient) and no sperm donations during treatment and up to 6 months after last dose of treatment.
* Female subjects who are breast feeding should agree to discontinue nursing prior to the first dose of study treatment and up to 6 months after the last study treatment.
* Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

General Exclusion Criteria:

* 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).
* Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected) or pre-existing liver cirrhosis.
* Known pre-existing interstitial lung disease (ILD). Bronchoemphysema is not considered as ILD.
* Other uncontrolled active illnesses or nonmalignant systemic disease (examples include, but are not limited to active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome ...).
* Any psychiatric, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
* Any malignancy (other than SCCHN, non-melanoma skin cancer or localized cervical cancer or localized and presumed cured prostatic cancer or basal cell carcinoma of the skin and carcinoma in situ of the cervix or bladder) within the last 3 years prior to treatment allocation.

Primary outcomes:
measure: Progression Free Survival Rate (PFSR) at week 16
timeFrame: The Progression Free Survival Rate (PFSR) analysis will be performed at week 16 for each patient in cohorts 1, 2 and 3.
measure: Objective response Rate (ORR) at week 16
timeFrame: Objective response Rate (ORR) at week 16 will be performed at week 16 for each patient in cohort 4.
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 54 months after first patient in
measure: Objective Response Rate
timeFrame: 48 months after first patient in
measure: Response duration
timeFrame: 54 months after first patient in
measure: Overall Survival (OS)
timeFrame: 54 months after first patient in
measure: Toxicity according CTCAE version 4.03
timeFrame: 54 months after first patient in
measure: Percentage of patients included in each patient cohort according the biomarker testing
timeFrame: 42 months after first patient in
measure: The percentage of patients with an evaluable fresh tumor biopsy
timeFrame: 42 months after first patient in
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Saint-Pierre-Site Porte de Hal
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussel
country: Belgium
facility: Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Haine-Saint-Paul
country: Belgium
facility: Hopital De Jolimont
city: Kortrijk
country: Belgium
facility: AZ Groeninge Kortrijk - Campus Kennedylaan
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen - Sint-Augustinus
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne - UCL Namur
city: Bordeaux
country: France
facility: CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
city: Dijon
country: France
facility: Centre Georges-Francois-Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Nantes
country: France
facility: Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe
city: Vandoeuvre Les Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Gustave Roussy
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: IRCCS - Fondazione G. Pascale
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
city: Barcelona
country: Spain
facility: ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Valencia
country: Spain
facility: Hospital Clinico Universitario De Valencia
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust (UHB) - UHB-Queen Elisabeth Medical Centre
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust - Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
Study officials:
References:
citation: 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.