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Carcinoma, Squamous Cell of Head and NeckPhase 2NCT01417936

Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy

A Phase 2 study testing Sym004 in people with Carcinoma, Squamous Cell of Head and Neck, run by Symphogen A/S at 10 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sym004
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
10 sitesin 3 countries
Study dates
Jul 2011to Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

10 sites in 3 countries.

10 sites in 3 countries

Germany6 sites

  • 4905; Charité Campus Benjamin Franklin; Hematology, Oncology and Transfusion Medicine

    Berlin, 12200

  • 4901; Universitätsklinikum Essen

    Essen, 45122

  • 4904; Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • 4906; University Medical Center Hamburg Eppendorf; Department of Otorhinolaryngology and Head and Neck Surgery

    Hamburg, 20246

  • 4907; University Hospital Heidelberg; Nationales Centrum für Tumorerkrankungen (NCT)

    Heidelberg, 6912

  • 4902; University of Leipzig

    Leipzig, 04103

Other trials in Germany

Belgium3 sites

  • 3203; Antwerp University Hospital; Department of Medical Oncology

    Antwerp, Edegem, 2650

  • 3202; Jules Bordet Institute; Clinique d'Oncologie Médicale

    Brussels, 1000

  • 3201; Cliniques Universitaires St-Luc; Centre du Cancer

    Brussels, 1200

Other trials in Belgium

France1 site

  • 3303; Centre Alexis Vautrin; Département d'Oncologie Médicale

    Nancy, Vandoeuvre Les Nancy, 54111

Other trials in France

About this study

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

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.

Being tested
Sym004
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sym004Drug

    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.

Study groups in NCT01417936
Study groupRoleWhat they receive
Sym004ExperimentalNot described
Receives: Drug: Sym004

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) Time

    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.

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

Secondary outcomes (15)

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

    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.

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

  2. Duration of Overall Response

    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.

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

  3. Time to Progression (TTP)

    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.

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

  4. Overall Survival Time

    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.

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

  5. Number of Subjects With Detectable Biomarkers at Any Visit

    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.

    Measured: Weeks 0 and 4; and 4 weeks after last dose

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

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

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

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

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

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

  8. Maximum Serum Concentration (Cmax)

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

  9. Minimum Serum Concentration (Cmin)

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

  10. Clearance (CL)

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

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

  11. Terminal Half Life (T1/2)

    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.

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

  12. Time to Reach Maximum Serum Concentration (Tmax)

    Measured: 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)

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

  14. Volume of Distribution (Vz)

    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.

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

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

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionOct 2012
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01417936
Sponsor's protocol ID
Sym004-02
Other IDs
2011-000902-24
Status last verified
Sep 2018
First submitted
15 Jul 2011
Last updated
15 Oct 2018
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Machiels JP, Specenier P, Krauss J, Dietz A, Kaminsky MC, Lalami Y, Henke M, Keilholz U, Knecht R, Skartved NJ, Horak ID, Pamperin P, Braun S, Gauler TC. A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol. 2015 Jul;76(1):13-20. doi: 10.1007/s00280-015-2761-4. Epub 2015 May 8.

    PubMed 25952795

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sym004 in people with Carcinoma, Squamous Cell of Head and Neck, run by Symphogen A/S at 10 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany, Belgium, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) Time (time frame: Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01417936, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.

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