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Completed

NCT Number: NCT01417936

Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

3203; Antwerp University Hospital; Department of Medical Oncology, Antwerp, Edegem, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sym004

Drug

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.

Primary outcomes

  1. Progression Free Survival (PFS) Time

    Time frame: Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeks

    The PFS time was defined as the time from first infusion of Sym004 until progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. or death. PD was 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 was also considered progression. Subjects who died without confirmed PD were considered as progressed. Subjects who died or showed PD more than 21 days after last treatment were censored (that is, were considered alive without progression on Day 21 after last treatment). Evaluation was done using Kaplan-Meier estimates.

Secondary outcomes

  1. Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)

    Time frame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months

    Best objective tumor response was 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 was defined as the occurrence of CR or PR according to RECIST Version 1.1. Disease control was 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.

  2. Duration of Overall Response

    Time frame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months

    Duration of overall response was 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 was objectively documented according to RECIST Version 1.1. Duration of overall response was censored at date of last imaging data of measured lesions if no confirmation of recurrence or PD was available.

  3. Time to Progression (TTP)

    Time frame: Time from first infusion of Sym04 until disease progression, assessed up to 18 months

    The TTP was defined as the time from first infusion of Sym004 until disease progression according to RECIST Version 1.1 criteria. Disease progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The subjects who died without prior assessment of PD were censored for TTP.

  4. Overall Survival Time

    Time frame: Time from first infusion of Sym004 until death, assessed up to 18 months

    Overall survival time was defined as the time from first infusion of Sym004 until date of death. Subjects who withdraw the consent or lost to follow-up were censored.

  5. Number of Subjects With Detectable Biomarkers at Any Visit

    Time frame: Weeks 0 and 4; and 4 weeks after last dose

    The biomarkers human papilloma virus (HPV), mutated epidermal growth factor receptor (EGFRvIII), c-MET and human epidermal growth factor receptor (HER) 2, HER3 were analyzed only in tumor cells while EGFR, phosphorylated epidermal growth factor receptor (pEGFR), and Ki-67 were analyzed both in tumor and skin biopsy cells.

  6. Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168])

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

    The AUC (0-168h) was estimated by determining the total area under the curve of the concentration versus time curve.

  7. Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf])

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

    The AUC (0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

  8. Maximum Serum Concentration (Cmax)

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

  9. Minimum Serum Concentration (Cmin)

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

  10. Clearance (CL)

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

    Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

  11. Terminal Half Life (T1/2)

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

    The apparent terminal half-life was defined as the time required for the serum concentration of Sym004 to decrease 50% in the final stage of its elimination.

  12. Time to Reach Maximum Serum Concentration (Tmax)

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

  13. Time to Reach Minimum Serum Concentration (Tmin)

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

  14. Volume of Distribution (Vz)

    Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3

    Volume of distribution was defined as the theoretical volume in which the total amount of drug needed to be uniformly distributed to produce the desired serum concentration of a drug.

  15. Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation

    Time frame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration

    An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Sponsors and collaborators

Lead sponsor

Symphogen A/S

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Aug 16, 2011
Registry last updated
Oct 15, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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