Clinical Trials /

Biomarker-based Study in R/M SCCHN

NCT03088059

Description:

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.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: EORTC-1559-HNCG
  • SECONDARY ID: 2017-000086-74
  • NCT ID: NCT03088059

Conditions

  • Carcinoma, Squamous Cell of Head and Neck

Interventions

DrugSynonymsArms
AfatinibPatient Cohort B1
PalbociclibPatient Cohort B3
standard of carePatient Cohort B1
IPH2201MonalizumabPatient Cohort I1
DurvalumabPatient Cohort I2
NiraparibPatient Cohort B4
BAY1163877RogaratinibPatient Cohort B6

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Patient Cohort B1ExperimentalPatients 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).
  • Afatinib
  • standard of care
Patient Cohort B2ExperimentalPatients 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)
  • Afatinib
  • standard of care
Patient Cohort B3ExperimentalPatients 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)
  • Palbociclib
  • standard of care
Patient Cohort B4ExperimentalPatients who are p16 negative and 'platinum sensitive' SCCHN will receive niraparib
  • Niraparib
Patient Cohort B5ExperimentalPatients whith oropharyngeal cancer and which are p16 positive will receive niraparib
  • Niraparib
Patient Cohort B6ExperimentalPatients with FGFR1/2/3 mRNA overexpression will receive rogaratinib
  • BAY1163877
Patient Cohort I1ExperimentalPatients who are anti-PD(L)1-naïeve or resistant (primary or secondary resistance) will receive IPH2201 antibody (monalizumab).
  • IPH2201
Patient Cohort I2ExperimentalPatient 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)
  • standard of care
  • IPH2201
  • Durvalumab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival Rate (PFSR) at week 16
Time Frame:The Progression Free Survival Rate (PFSR) analysis will be performed at week 16 for each patient in cohorts 1, 2 and 3.
Safety Issue:
Description:Progression Free Survival Rate (PFSR) at week 16 will be assessed as primary endpoint for all patients from cohorts 1, 2 and 3.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:54 months after first patient in
Safety Issue:
Description:
Measure:Objective Response Rate
Time Frame:48 months after first patient in
Safety Issue:
Description:Objective Response Rate will be measured according to both RECIST 1.1 and iRECIST
Measure:Response duration
Time Frame:54 months after first patient in
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:54 months after first patient in
Safety Issue:
Description:
Measure:Toxicity according CTCAE version 4.03
Time Frame:54 months after first patient in
Safety Issue:
Description:This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, for adverse event reporting.
Measure:Percentage of patients included in each patient cohort according the biomarker testing
Time Frame:42 months after first patient in
Safety Issue:
Description:
Measure:The percentage of patients with an evaluable fresh tumor biopsy
Time Frame:42 months after first patient in
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Organisation for Research and Treatment of Cancer - EORTC

Last Updated

November 4, 2019