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Biomarker-based Study in R/M SCCHN (UPSTREAM)

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ClinicalTrials.gov Identifier: NCT03088059
Recruitment Status : Recruiting
First Posted : March 23, 2017
Last Update Posted : July 12, 2018
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Squamous Cell of Head and Neck Drug: Afatinib Drug: Palbociclib Drug: standard of care Drug: IPH2201 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 205 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 16, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Patient Cohort 1
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, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care).
Drug: Afatinib
Afatinib 40 mg given orally, once daily, 1 cycle is 28 days

Drug: standard of care
Methotrexate, Paclitaxel, Docetaxel, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care

Experimental: Patient Cohort 2
Patients who are p16 negative and cetuximab naïve will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Drug: Afatinib
Afatinib 40 mg given orally, once daily, 1 cycle is 28 days

Drug: standard of care
Methotrexate, Paclitaxel, Docetaxel, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care

Experimental: Patient Cohort 3
Patients who are p16 negative and have an amplification of CCND1 will be randomized between palbociclib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
Drug: Palbociclib
Palbociclib 125 mg given orally, once daily, 1 cycle is 28 days (21 days on treatment, then 7 days off)

Drug: standard of care
Methotrexate, Paclitaxel, Docetaxel, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care

Experimental: Patient Cohort 4
Patients who are anti-PD(L)1-naïeve or resistant (primary or secondary resistance) will receive IPH2201 antibody (monalizumab).
Drug: IPH2201
Monalizumab given via intravenous injection, 10mg/kg, every 2 weeks
Other Name: Monalizumab




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

  2. Objective response Rate (ORR) at month 6 [ Time Frame: Objective response Rate (ORR) at month 6 will be performed at month 6 for each patient in cohort 4. ]
    Objective response Rate (ORR) at month 6 will be assessed as primary endpoint for all patients from cohort 4.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 54 months after first patient in ]
  2. Objective Response Rate [ Time Frame: 48 months after first patient in ]
    Objective Response Rate will be measured according to both RECIST 1.1 and iRECIST

  3. Response duration [ Time Frame: 54 months after first patient in ]
  4. Overall Survival (OS) [ Time Frame: 54 months after first patient in ]
  5. Toxicity according CTCAE version 4.03 [ Time Frame: 54 months after first patient in ]
    This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, for adverse event reporting.

  6. Percentage of patients included in each patient cohort according the biomarker testing [ Time Frame: 42 months after first patient in ]
  7. The percentage of patients with an evaluable fresh tumor biopsy [ Time Frame: 42 months after first patient in ]


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.


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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

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 3 weeks prior to treatment allocation. 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.
  • ECOG performance status 0 -1.
  • Tumor core biopsy from any accessible tumor site available for central testing.
  • Patients must have adequate organ function, evaluated within 14 days prior to treatment allocation.
  • 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).
  • Sexually active patients must use highly effective methods of contraception as of registration and up to 6 months after the last treatment dose.
  • Female subjects who are breast feeding should 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.
  • Any of the following within 6 months prior to treatment allocation: 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 or ejection fraction of less than 50%, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. Significant active cardiac disease including uncontrolled high blood pressure according to the CTCAE version 4.03 grade 3.
  • Nasopharynx and sino-nasal tumor.
  • Surgery or investigational drugs or chemotherapy or other anticancer therapy within 4 weeks before treatment allocation. Curative radiation therapy (60-70 Gy) within 8 weeks of treatment allocation. Palliative radiation therapy (e.g. 8 Gy on a painful lesion) will be allowed.
  • Known untreated and uncontrolled brain metastases or carcinomatous meningitis.
  • Known diagnosis of immune deficiency or a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Known 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 should not be considered as ILD.
  • Other uncontrolled active illnesses (active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes, …).
  • 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.

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): NCT03088059


Contacts
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Contact: EORTC HQ +32 2 774 1611 1559@eortc.org

Locations
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Belgium
ZNA Middelheim Recruiting
Antwerp, Belgium
Cliniques Universitaires Saint-Luc Recruiting
Brussel, Belgium
Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet Recruiting
Brussel, Belgium
Grand Hopital de Charleroi - Grand Hôpital de Charleroi - Site Notre Dame Recruiting
Charleroi, Belgium
Universitair Ziekenhuis Antwerpen Recruiting
Edegem, Belgium
Universitair Ziekenhuis Gent Recruiting
Gent, Belgium
Hopital De Jolimont Recruiting
Haine-Saint-Paul, Belgium
AZ Groeninge Kortrijk - Campus Kennedylaan Recruiting
Kortrijk, Belgium
U.Z. Leuven - Campus Gasthuisberg Not yet recruiting
Leuven, Belgium
GasthuisZusters Antwerpen - Sint-Augustinus Recruiting
Wilrijk, Belgium
CHU Dinant Godinne - UCL Namur Recruiting
Yvoir, Belgium
France
CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre Recruiting
Bordeaux, France
Centre Georges-Francois-Leclerc Recruiting
Dijon, France
Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau Recruiting
Nantes, France
Centre Antoine Lacassagne Recruiting
Nice, France
Institut Curie Recruiting
Paris, France
Institut de Cancérologie de Lorraine Recruiting
Vandoeuvre Les Nancy, France
Gustave Roussy Recruiting
Villejuif, France
Italy
Azienda Ospedaliera Papa Giovanni XXIII Not yet recruiting
Bergamo, Italy
Ospedale Bellaria Not yet recruiting
Bologna, Italy
Azienda Ospedaliero-Universitaria Careggi Not yet recruiting
Firenze, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori Recruiting
Milano, Italy
Ospedale San Paolo Not yet recruiting
Milano, Italy
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Not yet recruiting
Napoli, Italy
United Kingdom
University Hospitals Birmingham NHS Foundation Trust (UHB) - UHB-Queen Elisabeth Medical Centre Not yet recruiting
Birmingham, United Kingdom
NHS Lothian - Western General Hospital Not yet recruiting
Edinburgh, United Kingdom
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital Not yet recruiting
Glasgow, United Kingdom
Guy's and St Thomas' NHS - Guy s and St Thomas' NHS - Guy's Hospital Not yet recruiting
London, United Kingdom
Oxford University Hospitals NHS Trust - Churchill Hospital Not yet recruiting
Oxford, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital Not yet recruiting
Sheffield, United Kingdom
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC

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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT03088059     History of Changes
Other Study ID Numbers: EORTC-1559-HNCG
2017-000086-74 ( EudraCT Number )
First Posted: March 23, 2017    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms, Squamous Cell
Paclitaxel
Docetaxel
Gemcitabine
Methotrexate
Fluorouracil
Palbociclib
Afatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs