Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Sym004 in Subjects With Squamous Cell Carcinoma of Head and Neck (SCCHN) Failing Anti-Epidermal Growth Factor Receptor (Anti-EGFR) Based Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01417936
First received: July 15, 2011
Last updated: November 27, 2014
Last verified: November 2014
  Purpose

The trial is designed as a multi-center, open label Phase 2 trial that investigates the efficacy and safety of Sym004 in subjects with squamous cell cancer of the head and neck (SCCHN). Subjects included must have responded to previous anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-based therapy and subsequently become resistant to that therapy. It is believed that Sym004 has the potential to induce tumor responses and provide a superior treatment option to subjects with advanced SCCHN.

Symphogen was the sponsor for planning/conducting and reporting results for this trial.


Condition Intervention Phase
Carcinoma, Squamous Cell of Head and Neck
Biological: Sym004
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Single Arm, Phase II Trial to Investigate the Safety and Efficacy of Sym004 in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Who Have Failed Anti-EGFR Monoclonal Antibody-based Therapy

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Progression Free Survival (PFS) Time [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    The PFS time is defined as the time from first infusion of Sym004 until progressive disease (PD) or death according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The unequivocal progression of existing non-target lesions and the appearance of one or more lesions is also considered progression. Subjects who die without confirmed PD will be considered as progressed. Subjects who die or show PD more than 21 days after last treatment will be censored (that is, will be considered alive without progression on Day 21 after last treatment). Evaluation will be done using Kaplan-Meier estimates.


Secondary Outcome Measures:
  • Objective Tumor Response and derived endpoints (Objective Response Rate and Disease Control Rate) [ Time Frame: Time from randomization until disease progression, death or last tumor assessment, reported between day of first subject randomized, that is, Jul 2011 until cut-off date, (08 Oct 2012) ] [ Designated as safety issue: No ]

    Best objective tumor response is defined as the occurrence of complete response (CR), partial response (PR), stable disease (SD), or PD according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

    Objective response is defined as the occurrence of CR or PR according to RECIST Version 1.1.

    Disease control is defined as the occurrence of CR, PR or SD according to RECIST Version 1.1.

    CR: Disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm; PR: At least a 30% decrease in the sum of diameters of all - lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial.


  • Duration of Overall Response [ Time Frame: Time from randomization until disease progression, death or last tumor assessment, reported between day of first subject randomized, that is, Jul 2011 until cut-off date, (08 Oct 2012) ] [ Designated as safety issue: No ]
    Duration of overall response is defined as the time from the first time point where measurement criteria are met for CR or PR until first date of recurrence or PD is objectively documented according to RECIST Version 1.1. Duration of overall response will be censored at date of last imaging data of measured lesions if no confirmation of recurrence or PD is available.

  • Time to Progression (TTP) [ Time Frame: Time from randomization until disease progression, death or last tumor assessment, reported between day of first subject randomized, that is, Jul 2011 until cut-off date, (08 Oct 2012) ] [ Designated as safety issue: No ]
    The TTP is defined as the time from first infusion of Sym004 until disease progression according to RECIST Version 1.1 criteria. The subjects who die without prior assessment of PD will be censored for TTP.

  • Overall Survival Time [ Time Frame: Time from randomization until death or last day known to be alive, reported between day of first subject randomized, that is, Jul 2011 until survival cut-off date, (05 Dec 2012) ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from first infusion of Sym004 until date of death. Subjects will be censored if they withdraw the consent or lost to follow-up.

  • Number of Subjects with Detectable Biomarkers [ Time Frame: Weeks 0 and 4; and 4 weeks after last dose ] [ Designated as safety issue: No ]
    The biomarkers human papilloma virus (HPV), (EGFRvIII), c-MET protocol oncogene (cMET) and human epidermal growth factor receptor (HER) 2, HER3 will be analyzed only in tumor cells while EGFR, phosphorylated epidermal growth factor receptor (pEGFR), and Ki-67 will be analyzed both in tumor and skin biopsy cells.

  • Area under the serum concentration curve from time zero to 168 hours (AUC [0-168]) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
    The AUC (0-168h) will be estimated by determining the total area under the curve of the concentration versus time curve.

  • Area under the serum concentration curve from time zero to infinity (AUC [0-inf]) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
    The AUC (0-inf) will be estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

  • Maximum serum concentration (Cmax) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
  • Minimum serum concentration (Cmin) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
  • Clearance (CL) ((mL/h/Kg) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

  • Terminal half life (T1/2) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
    The apparent terminal half-life will be defined as the time required for the serum concentration of Sym004 to decrease 50% in the final stage of its elimination.

  • Time of maximum serum concentration (Tmax) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
  • Time of minimum serum concentration (Tmin) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
  • Volume of distribution (Vz) (mL/kg) [ Time Frame: Pre-treatment, end of infusion, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 3 ] [ Designated as safety issue: No ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.

  • Number of subjects with adverse events (AEs), Serious AEs, treatment emergent AEs, AEs leading to death [ Time Frame: Time from randomization to the data cut-off date Oct 2012 ] [ Designated as safety issue: Yes ]
    Any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug.


Enrollment: 26
Study Start Date: July 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sym004 Biological: Sym004
Sym004 will be administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis initially or at relapse of SCCHN of the oral cavity, oropharynx, hypopharynx or larynx
  • Recurrent and/or metastatic SCCHN not amenable to curative treatment with surgery and/or (chemo)radiation
  • Previous treatment with an anti-EGFR monoclonal antibody (mAb) in the palliative setting either as monotherapy or in combination with chemotherapy or radiotherapy and showing:

    • Documented clinical benefit or response for at least 8 weeks (PR, CR or SD) on the anti-EGFR mAb-based therapy and
    • Documented disease progression (verified by computed tomography [CT] scan or magnetic resonance imaging [MRI] according to RECIST (1.1) during or within 12 weeks following the last administration of anti-EGFR mAb
  • Accessible tumor for biopsy and subject acceptance of repeat tumor biopsies
  • Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

  • More than 2 lines of prior chemotherapy in the palliative setting
  • Expected survival <12 weeks
  • Subjects with known brain metastases
  • Chemotherapy or radiation therapy within 21 days prior to Visit 2 at the exception of palliative radiotherapy for bleeding or pain, which is allowed anytime, if not given on target lesions
  • Anti-EGFR mAbs within 14 days prior to Visit 2
  • Major surgery within 4 weeks prior to Visit 2 and subjects must have recovered from effects of major surgery
  • Other protocol-defined exclusion criteria could apply
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01417936

Locations
Belgium
3203; Antwerp University Hospital; Department of Medical Oncology
Antwerp, Edegem, Belgium, 2650
3202; Jules Bordet Institute; Clinique d'Oncologie Médicale
Bruxelles, Belgium, 1000
3201; Cliniques Universitaires St-Luc; Centre du Cancer
Bruxelles, Belgium, 1200
France
3303; Centre Alexis Vautrin; Département d'Oncologie Médicale
Nancy, Vandoeuvre Les Nancy, France, 54111
Germany
4905; Charité Campus Benjamin Franklin; Hematology, Oncology and Transfusion Medicine
Berlin, Germany, 12200
4901; Universitätsklinikum Essen
Essen, Germany, 45122
4904; Universitätsklinikum Freiburg
Freiburg, Germany, 79106
4906; University Medical Center Hamburg Eppendorf; Department of Otorhinolaryngology and Head and Neck Surgery
Hamburg, Germany, 20246
4907; University Hospital Heidelberg; Nationales Centrum für Tumorerkrankungen (NCT)
Heidelberg, Germany, 6912
4902; University of Leipzig
Leipzig, Germany, 04103
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Responsible Symphogen A/S, Lyngby, Denmark
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01417936     History of Changes
Other Study ID Numbers: Sym004-02
Study First Received: July 15, 2011
Last Updated: November 27, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Agence française de sécurité sanitaire des produits de santé (Afssaps)
Germany: Paul-Erhlich-Institut, Federal Institute for Vaccines and Biomedicines

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell

ClinicalTrials.gov processed this record on February 27, 2015