Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Sym004

About this trial

This is an interventional treatment trial for Carcinoma, Squamous Cell of Head and Neck

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

3203; Antwerp University Hospital; Department of Medical Oncology
3202; Jules Bordet Institute; Clinique d'Oncologie Médicale
3201; Cliniques Universitaires St-Luc; Centre du Cancer
3303; Centre Alexis Vautrin; Département d'Oncologie Médicale
4905; Charité Campus Benjamin Franklin; Hematology, Oncology and Transfusion Medicine
4901; Universitätsklinikum Essen
4904; Universitätsklinikum Freiburg
4906; University Medical Center Hamburg Eppendorf; Department of Otorhinolaryngology and Head and Neck Surgery
4907; University Hospital Heidelberg; Nationales Centrum für Tumorerkrankungen (NCT)
4902; University of Leipzig

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sym004

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Maximum Serum Concentration (Cmax)

Minimum Serum Concentration (Cmin)

Clearance (CL)

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

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.

Time to Reach Maximum Serum Concentration (Tmax)

Time to Reach Minimum Serum Concentration (Tmin)

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.

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.

Full Information

NCT ID

NCT01417936

First Posted

July 15, 2011

Last Updated

September 13, 2018

Sponsor

Symphogen A/S

1. Study Identification

Unique Protocol Identification Number

NCT01417936

Brief Title

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

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

July 2011 (undefined)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Symphogen A/S

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Squamous Cell of Head and Neck

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sym004

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Sym004

Intervention Description

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 Outcome Measure Information:

Title

Progression Free Survival (PFS) Time

Description

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

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

Title

Duration of Overall Response

Description

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.

Time Frame

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

Title

Time to Progression (TTP)

Description

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.

Time Frame

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

Title

Overall Survival Time

Description

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.

Time Frame

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

Title

Number of Subjects With Detectable Biomarkers at Any Visit

Description

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.

Time Frame

Weeks 0 and 4; and 4 weeks after last dose

Title

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

Description

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

Time Frame