Clinical trial NCT01417936: Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Squamous Cell of Head and Neck
Lead sponsor: Symphogen A/S
Sponsor class: INDUSTRY
First posted: 2011-08-16
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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). 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.


Eligibility 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

Primary outcomes:
measure: Progression Free Survival (PFS) Time
timeFrame: Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeks
Secondary outcomes:
measure: Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)
timeFrame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months
measure: Duration of Overall Response
timeFrame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months
measure: Time to Progression (TTP)
timeFrame: Time from first infusion of Sym04 until disease progression, assessed up to 18 months
measure: Overall Survival Time
timeFrame: Time from first infusion of Sym004 until death, assessed up to 18 months
measure: Number of Subjects With Detectable Biomarkers at Any Visit
timeFrame: Weeks 0 and 4; and 4 weeks after last dose
measure: Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168])
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf])
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Maximum Serum Concentration (Cmax)
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Minimum Serum Concentration (Cmin)
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Clearance (CL)
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Terminal Half Life (T1/2)
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Time to Reach Maximum Serum Concentration (Tmax)
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Time to Reach Minimum Serum Concentration (Tmin)
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Volume of Distribution (Vz)
timeFrame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
measure: Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation
timeFrame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: 3203; Antwerp University Hospital; Department of Medical Oncology
state: Edegem
city: Bruxelles
country: Belgium
facility: 3202; Jules Bordet Institute; Clinique d'Oncologie Médicale
city: Bruxelles
country: Belgium
facility: 3201; Cliniques Universitaires St-Luc; Centre du Cancer
city: Nancy
country: France
facility: 3303; Centre Alexis Vautrin; Département d'Oncologie Médicale
state: Vandoeuvre Les Nancy
city: Berlin
country: Germany
facility: 4905; Charité Campus Benjamin Franklin; Hematology, Oncology and Transfusion Medicine
city: Essen
country: Germany
facility: 4901; Universitätsklinikum Essen
city: Freiburg
country: Germany
facility: 4904; Universitätsklinikum Freiburg
city: Hamburg
country: Germany
facility: 4906; University Medical Center Hamburg Eppendorf; Department of Otorhinolaryngology and Head and Neck Surgery
city: Heidelberg
country: Germany
facility: 4907; University Hospital Heidelberg; Nationales Centrum für Tumorerkrankungen (NCT)
city: Leipzig
country: Germany
facility: 4902; University of Leipzig
Study officials:
affiliation: Symphogen A/S
name: Ivan Horak, MD, FACP
role: STUDY_DIRECTOR
References:
citation: 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.