RESGEX: CetuGEX™ in Comparison to Cetuximab for the Treatment of Patients With Head and Neck Cancer

• Sponsor: Glycotope GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02052960
• Collaborator: (none)
• Enrollment: 240
• Locations: 34
• Arms: 2
• Actual Duration (Months): 44.1
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The aim of the study is to evaluate the efficacy of CetuGEX™ for the treatment of patients with stage III/IV recurrent and/or metastatic SCCHN as compared to cetuximab (both in combination with platinum-based chemotherapy) in terms of progression-free survival (PFS).

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Squamous Cell of Head and Neck	Drug: CetuGEX™; Drug: Cetuximab; Drug: Chemotherapy	Phase 2

Detailed Description

Indication: First line systemic treatment for stage III/IV recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)

Primary Objective:

To evaluate the efficacy of CetuGEX™ for the treatment of patients with stage III/IV recurrent and/or metastatic SCCHN as compared to cetuximab (both in combination with platinum-based chemotherapy) in terms of progression-free survival (PFS).

Secondary Objectives:

To evaluate further efficacy criteria, safety and quality of life (QoL) of patients with stage III/IV recurrent and/or metastatic SCCHN treated with CetuGEX™ as compared to cetuximab (both in combination with platinum-based chemotherapy).

To assess pharmacokinetic (PK) parameters and profiles of CetuGEX™. To assess efficacy and safety based on genetic markers for immune response (Fc-gamma receptor [FcγR] allotypes) and biomarkers (exploratory only).

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Controlled, Open Label, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of CetuGEX™ Plus CT in Comparison to Cetuximab Plus CT in Patients With Stage III/IV Recurrent and/or Metastatic SCCHN
• Actual Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Aug 28, 2017
• Actual Study Completion Date: Oct 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CetuGEX™ plus chemotherapy 720 mg weekly administration	Drug: CetuGEX™; 60 mg/day 0, 930 mg/day 1, followed by 720 mg i.v. weekly administration; Other Names: Tomuzotuximab ; Drug: Chemotherapy; Combination of Cisplatin and 5-Fluorouracil (Carboplatin may substitute Cisplatin following the 1st cycle of therapy in case of toxicity); Other Names: Combination of Cisplatin and 5-Fluorouracil
Active Comparator: Cetuximab plus chemotherapy 250 mg/m2 weekly administration	Drug: Cetuximab; 400 mg/sqm body surface area (BSA) on day 1, followed by 250 mg/sqm BSA i.v. weekly administration; Other Names: Erbitux® ; Drug: Chemotherapy; Combination of Cisplatin and 5-Fluorouracil (Carboplatin may substitute Cisplatin following the 1st cycle of therapy in case of toxicity); Other Names: Combination of Cisplatin and 5-Fluorouracil

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [The PFS was defined as time from randomization until disease progression or death of any cause, up to 24 month]

   The primary efficacy endpoint was PFS as assessed by the investigator. Date of disease progression was defined as the date of imaging (based on computed tomography (CT) scans or magnetic resonance imaging (MRI)) showing disease progression, as assessed by the investigator according to adapted immune-related RECIST 1.1 (modified irRC). Disease progression was defined as a 20% increase in tumor burden, taking as reference the smallest tumor burden recorded since the treatment started; confirmation by a second scan was not required. The PFS time was censored at the time of the last tumor assessment if the patient was alive and without progression at the last time of observation.

Secondary Outcome Measures

1. Objective Response Rate (ORR) [Time from randomization until disease progression or death, whichever occurs first, up to 24 month.]

   Objective response rate is the percentage of patients with a tumor size reduction of a predefined amount for a minimum time period and it is defined as the sum of complete responses (CR) and partial responses (PR). CR: Disappearance of all non-nodal target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the tumor burden (sum of the longest lesion diameter (LD) of target lesions (including the short axes of any target lymph nodes plus measurable new lesions), taking as reference the baseline sum diameters.

2. Clinical Benefit Rate [Time from randomization until disease progression or death, whichever occurs first, up to 24 month.]

   The clinical benefit rate is the percentage of patients with an objective response or stable disease (SD). SD is defined as not meeting criteria of complete response and partial response, in absence of meeting criteria for disease progression. Follow-up measurements must have met the SD criteria at least once after randomization at a minimum interval of 8 weeks.

3. Time to Treatment Failure [Time to treatment failure, defined as the interval between the date of randomization and the date of treatment discontinuation for any reason, up to 24 month.]

   Time to treatment failure is defined as the time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.

4. Overall Survival [Time from randomization to the time of death, up to 24 month.]

   The overall survival is defined as the duration of time from randomization to the time of death.

5. Time of Global Health Status Deterioration [From randomization up to end-of study visit, up to 24 month]

   Quality of Life (QoL) scores as assessed by European Oncology Research Trials Committee (EORTC) QoL questionnaires (QLQ) EORTC-QLQ-C30. Scores are on a scale of 0 to 100, where 100 represents the highest possible QoL.Time to first deterioration of at least 10 points.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with histologically confirmed recurrent and/or metastatic SCCHN not eligible for local treatment.

2. Patients with measurable disease according to RECIST 1.1.

3. Patients aged at least 18 years at screening.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. Minimum life expectancy of 3 months.

6. Tissue samples available for specific and therapy-related biological assessments.

7. If female and of childbearing potential, was non-lactating and had negative pregnancy test results at screening and prior to randomization.

8. If female, was either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or willing to use highly effective contraceptives during study participation until 6 months after last administration of any study medication, particularly cisplatin or carboplatin, with a failure rate <1% according to the Note for Guidance on non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals (CPMP/ICH/286/95) of the European Medicines Agency. Male patients who had partners of childbearing potential had to confirm adequate use of highly effective contraceptives during study participation until 6 months after last administration of any study medication, particularly cisplatin or carboplatin, as well.

9. Willing and able to comply with the protocol.

10. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to randomization.

2. Cetuximab or other epidermal growth factor receptor (EGFR)-targeting agent treatment, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to randomization.

3. Surgery (other than minor interventions like diagnostic biopsy or intravenous port implantation) or irradiation within 30 days before randomization.

4. Concomitant antitumor therapy or concomitant immunotherapy, live vaccines including yellow fever vaccination (as per cisplatinum Summary of Product Characteristics [SmPC]).

5. Concomitant corticosteroid treatment unless specified within the protocol.

6. Clinical evidence of brain metastasis or leptomeningeal involvement.

7. Patients with nasopharyngeal tumors.

8. Concomitant malignant disease, except for adequately treated tumors with high likelihood of being cured (e.g., basal cell cancer of the skin, cervical cancer or breast cancer in situ). Patients with previous malignancies but without evidence of disease for at least 5 years were allowed to enter the study.

9. Patients with renal or hepatic impairment (serum creatinine and bilirubin >1.5 fold above the upper limit of normal ranges, creatinine clearance <60 mL/min, and transaminase >5-fold above the upper limit of normal ranges) and patients with hematology parameters outside the normal ranges (hemoglobin <9 g/dL, absolute neutrophil count <1500/mm3 and platelet count <105/mm3) at screening as well as patients with impaired auditory function or platinum-related neuropathy.

10. Clinically active infections ≥Grade 2 using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 and/or requiring intravenous antibiotics.

11. Known active hepatitis B or C.

12. Known human immunodeficiency virus (HIV) infection.

13. Myocardial infarction within 6 months prior to screening.

14. Symptomatic congestive heart failure (New York Heart Association Grade 3 or 4), unstable angina pectoris within 6 months prior to screening, significant cardiac arrhythmia, history of stroke, or transient ischemic attack within 1 year prior to screening.

15. History of keratitis requiring medical interventions within the last 5 years or interstitial lung disease.

16. Patients with any other disorder that, in the opinion of the investigator, might have interfered with the conduct of the study.

17. Patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol.

18. Patients institutionalized by official means or court order.

19. Receipt of any other IMP within the last 30 days before randomization or any previous CetuGEX™ administration.

20. Prior allergic reaction to a monoclonal antibody, grade 3 infusion related reaction (IRR) or any grade 4 reaction to a monoclonal antibody.

21. Known sensitivity to any component of the IMP and medication used in this study.

22. Known dihydropyrimidine dehydrogenase deficiency (France only).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Glycotope-contracted Research Facility	Antwerp		Belgium	2650
2	Glycotope-contracted Research Facility	Brussels		Belgium	1000
3	Glycotope-contracted Research Facility	Brussels		Belgium	1200
4	Glycotope-contracted Research Facility	Gent		Belgium	9000
5	Glycotope-contracted Research Facility	Avignon		France	84918
6	Glycotope-contracted Research Facility	Lille		France	59020
7	Glycotope-contracted Research Facility	Lyon		France	69008
8	Glycotope-contracted Research Facility	Nice		France	06189
9	Glycotope-contracted Research Facility	St Herblain		France	44805
10	Glycotope-contracted Research Facility	Aachen		Germany	52074
11	Glycotope-contracted Research Facility	Berlin		Germany	12203
12	Glycotope-contracted Research Facility	Dresden		Germany	01307
13	Glycotope-contracted Research Facility	Essen		Germany	45122
14	Glycotope-contracted Research Facility	Hamburg		Germany	20246
15	Glycotope-contracted Research Facillity	Hannover		Germany	30625
16	Glycotope-contracted Research Facility	Leipzig		Germany	04103
17	Gycotope-contracted Research Facility	Milan		Italy	20142
18	Glycotope-contracted Research Facility	Pavia		Italy	27100
19	Glycotope-contracted Research Facility	Bydgoszcz		Poland	85-796
20	Glycotope-contracted Research Facility	Krakow		Poland
21	Glycotope-contracted Research Facility	Lodz		Poland	93-513
22	Glycotope-contracted Research Facility	Lublin		Poland	20-090
23	Glycotope-contracted Research Facility	Warsaw		Poland	2781
24	Glycotope-contracted Research Facility	Brasov		Romania	500091
25	Glycotope-contracted Research Facility	Clui-Napoca		Romania	400015
26	Glycotope-contracted Research Facility	Craiova		Romania	200385
27	Glycotope-contracted Research Facility	Oradea		Romania	410469
28	Glycotope-contracted Research Facility	Ploiesti		Romania	100011
29	Glycotope-contracted Research Facility	Timisoara		Romania	300167
30	Glycotope-contracteed Research Facility	Timisoara		Romania	300239
31	Glycotope-contracted Research Facility	Barcelona		Spain	08036
32	Glycotope-contracted Research Facility	Madrid		Spain	28050
33	Glycotope-contracted Research Facility	Madrid		Spain	28911
34	Glycotope-contracted Research Facility	Valencia		Spain	46009

Sponsors and Collaborators

• Glycotope GmbH

Investigators

• Principal Investigator: Ulrich Keilholz, Prof, Charite University, Berlin, Germany

Study Documents (Full-Text)

• Study Protocol - Feb 6, 2015
• Statistical Analysis Plan - Dec 21, 2016

More Information

Publications

None provided.

• Responsible Party: Glycotope GmbH
• ClinicalTrials.gov Identifier: NCT02052960
• Other Study ID Numbers: GEXMab52201; 2013-000931-28
• First Posted: Feb 3, 2014
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Glycotope GmbH: tomuzotuximab; cetuximab; SCCHN
• Additional relevant MeSH terms: Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Cisplatin; Fluorouracil; Cetuximab

Study Results

Participant Flow

Arm/Group Title	CetuGEX in Combination With Chemotherapy	Cetuximab in Combination With Chemotherapy
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly. Chemotherapy consisted of 5-FU (1000 mg/m2/d, day 1-4) and cisplatin (100 mg/m2, on day 1).Treatment cycles were scheduled to be repeated every 3 weeks for a maximum of 6 cycles, and followed by a weekly single-agent maintenance therapy of CetuGEX.	Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA. Chemotherapy consisted of 5-FU (1000 mg/m2/d, day 1-4) and cisplatin (100 mg/m2, on day 1).Treatment cycles were scheduled to be repeated every 3 weeks for a maximum of 6 cycles, and followed by a weekly single-agent maintenance therapy of cetuximab.
Period Title: Overall Study
STARTED	117	123
Treated Patients	115	122
COMPLETED	63	77
NOT COMPLETED	54	46

Baseline Characteristics

Arm/Group Title	CetuGEX™ Plus Chemotherapy	Cetuximab Plus Chemotherapy	Total
Arm/Group Description	720 mg weekly administration CetuGEX™: 60 mg/day 0, 930 mg/day 1, followed by 720 mg i.v. weekly administration Chemotherapy: Combination of Cisplatin and 5-Fluorouracil (Carboplatin may substitute Cisplatin following the 1st cycle of therapy in case of toxicity)	250 mg/m2 weekly administration Cetuximab: 400 mg/sqm body surface area (BSA) on day 1, followed by 250 mg/sqm BSA i.v. weekly administration Chemotherapy: Combination of Cisplatin and 5-Fluorouracil (Carboplatin may substitute Cisplatin following the 1st cycle of therapy in case of toxicity)	Total of all reporting groups
Overall Participants	117	123	240
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	88 75.2%	89 72.4%	177 73.8%
>=65 years	29 24.8%	34 27.6%	63 26.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.8 (7.54)	59.8 (7.91)	59.8 (7.72)
Sex: Female, Male (Count of Participants)
Female	18 15.4%	17 13.8%	35 14.6%
Male	99 84.6%	106 86.2%	205 85.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Romania	24 20.5%	19 15.4%	43 17.9%
Belgium	5 4.3%	8 6.5%	13 5.4%
Poland	29 24.8%	29 23.6%	58 24.2%
Italy	1 0.9%	7 5.7%	8 3.3%
France	19 16.2%	25 20.3%	44 18.3%
Germany	33 28.2%	29 23.6%	62 25.8%
Spain	6 5.1%	6 4.9%	12 5%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	The primary efficacy endpoint was PFS as assessed by the investigator. Date of disease progression was defined as the date of imaging (based on computed tomography (CT) scans or magnetic resonance imaging (MRI)) showing disease progression, as assessed by the investigator according to adapted immune-related RECIST 1.1 (modified irRC). Disease progression was defined as a 20% increase in tumor burden, taking as reference the smallest tumor burden recorded since the treatment started; confirmation by a second scan was not required. The PFS time was censored at the time of the last tumor assessment if the patient was alive and without progression at the last time of observation.
Time Frame	The PFS was defined as time from randomization until disease progression or death of any cause, up to 24 month

Outcome Measure Data

Analysis Population Description

Intent-to-treat-population

Arm/Group Title	CetuGEX	Cetuximab
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly	Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA.
Measure Participants	117	123
Median (95% Confidence Interval) [weeks]	27.7	26.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CetuGEX, Cetuximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.000
	Confidence Interval	(2-Sided) 95%; 0.736 to 1.359
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Objective response rate is the percentage of patients with a tumor size reduction of a predefined amount for a minimum time period and it is defined as the sum of complete responses (CR) and partial responses (PR). CR: Disappearance of all non-nodal target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the tumor burden (sum of the longest lesion diameter (LD) of target lesions (including the short axes of any target lymph nodes plus measurable new lesions), taking as reference the baseline sum diameters.
Time Frame	Time from randomization until disease progression or death, whichever occurs first, up to 24 month.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	CetuGEX	Cetuximab
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly.	Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA.
Measure Participants	117	123
Count of Participants [Participants]	52 44.4%	57 46.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CetuGEX, Cetuximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -14.5 to 10.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinical Benefit Rate
Description	The clinical benefit rate is the percentage of patients with an objective response or stable disease (SD). SD is defined as not meeting criteria of complete response and partial response, in absence of meeting criteria for disease progression. Follow-up measurements must have met the SD criteria at least once after randomization at a minimum interval of 8 weeks.
Time Frame	Time from randomization until disease progression or death, whichever occurs first, up to 24 month.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	CetuGEX	Cetuximab
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly	Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA.
Measure Participants	117	123
Count of Participants [Participants]	88 75.2%	94 76.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CetuGEX, Cetuximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.21
	Confidence Interval	(2-Sided) 95%; -12.05 to 9.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure is defined as the time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.
Time Frame	Time to treatment failure, defined as the interval between the date of randomization and the date of treatment discontinuation for any reason, up to 24 month.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CetuGEX	Cetuximab
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly	Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA.
Measure Participants	116	123
Median (95% Confidence Interval) [weeks]	22.1	23.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CetuGEX, Cetuximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.057
	Confidence Interval	(2-Sided) 95%; 0.814 to 1.372
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Overall Survival
Description	The overall survival is defined as the duration of time from randomization to the time of death.
Time Frame	Time from randomization to the time of death, up to 24 month.

Outcome Measure Data

Analysis Population Description

Intent-to-treat- population

Arm/Group Title	CetuGEX	Cetuximab
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly.	Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA.
Measure Participants	117	123
Median (95% Confidence Interval) [weeks]	49.7	59.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CetuGEX, Cetuximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.012
	Confidence Interval	(2-Sided) 95%; 0.734 to 1.396
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Time of Global Health Status Deterioration
Description	Quality of Life (QoL) scores as assessed by European Oncology Research Trials Committee (EORTC) QoL questionnaires (QLQ) EORTC-QLQ-C30. Scores are on a scale of 0 to 100, where 100 represents the highest possible QoL.Time to first deterioration of at least 10 points.
Time Frame	From randomization up to end-of study visit, up to 24 month

Outcome Measure Data

Analysis Population Description

Intent-to treat population. 158 patients were evaluable for this Outcome Measure.

Arm/Group Title	CetuGEX in Combination With Chemotherapy	Cetuximab in Combination With Chemotherapy
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly. Chemotherapy consisted of 5-FU (1000 mg/m2/d, day 1-4) and cisplatin (100 mg/m2, on day 1).Treatment cycles were scheduled to be repeated every 3 weeks for a maximum of 6 cycles, and followed by a weekly single-agent maintenance therapy of CetuGEX.	Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA. Chemotherapy consisted of 5-FU (1000 mg/m2/d, day 1-4) and cisplatin (100 mg/m2, on day 1).Treatment cycles were scheduled to be repeated every 3 weeks for a maximum of 6 cycles, and followed by a weekly single-agent maintenance therapy of cetuximab.
Measure Participants	76	82
Median (Inter-Quartile Range) [weeks]	43.4	31.3

Adverse Events

Time Frame	up to 24 month
Arm/Group Title	CetuGEX		Cetuximab
Arm/Group Description	CetuGEX™ was administered as infusion to all patients randomized to the CetuGEX™ arm, once weekly. The initial dose was 990 mg and subsequent doses were 720 mg once weekly		Cetuximab was administered once weekly as infusion to all patients randomized to the cetuximab arm.The initial dose was 400 mg/m2 body surface area (BSA) and each subsequent dose was 250 mg/m2 BSA.
All Cause Mortality
	CetuGEX		Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/115 (17.4%)		14/122 (11.5%)
Serious Adverse Events
	CetuGEX		Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/115 (60.9%)		78/122 (63.9%)
Blood and lymphatic system disorders
Anemia	9/115 (7.8%)		9/122 (7.4%)
Neutropenia	8/115 (7%)		7/122 (5.7%)
Thrombocytopenia	2/115 (1.7%)		4/122 (3.3%)
Febrile neutropenia	3/115 (2.6%)		2/122 (1.6%)
Leucopenia	1/115 (0.9%)		4/122 (3.3%)
Cardiac disorders
Myocardial infarction	2/115 (1.7%)		1/122 (0.8%)
Gastrointestinal disorders
Diarrhoea	3/115 (2.6%)		2/122 (1.6%)
Nausea	3/115 (2.6%)		2/122 (1.6%)
Vomiting	2/115 (1.7%)		2/122 (1.6%)
General disorders
General physical health deterioration	2/115 (1.7%)		2/122 (1.6%)
Device dislocation	1/115 (0.9%)		2/122 (1.6%)
Fatigue	2/115 (1.7%)		1/122 (0.8%)
Mucosal inflammation	3/115 (2.6%)		0/122 (0%)
Infections and infestations
Pneumonia	12/115 (10.4%)		9/122 (7.4%)
Sepsis	3/115 (2.6%)		7/122 (5.7%)
Device related infection	5/115 (4.3%)		4/122 (3.3%)
Lung abscess	0/115 (0%)		3/122 (2.5%)
Investigations
Blood creatinine increased	2/115 (1.7%)		3/122 (2.5%)
Metabolism and nutrition disorders
Dehydration	4/115 (3.5%)		5/122 (4.1%)
Hypomagnesaemia	4/115 (3.5%)		5/122 (4.1%)
Hypokalaemia	3/115 (2.6%)		4/122 (3.3%)
Decreased appetite	2/115 (1.7%)		3/122 (2.5%)
Nervous system disorders
Cerebrovascular accident	2/115 (1.7%)		1/122 (0.8%)
Renal and urinary disorders
Renal failure	2/115 (1.7%)		1/122 (0.8%)
Renal failure acute	1/115 (0.9%)		2/122 (1.6%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/115 (1.7%)		3/122 (2.5%)
Vascular disorders
Hypotension	3/115 (2.6%)		2/122 (1.6%)
Other (Not Including Serious) Adverse Events
	CetuGEX		Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	114/115 (99.1%)		121/122 (99.2%)
Blood and lymphatic system disorders
Anaemia	44/115 (38.3%)	104	56/122 (45.9%)	152
Neutropenia	47/115 (40.9%)	105	51/122 (41.8%)	124
Leukopenia	33/115 (28.7%)	98	37/122 (30.3%)	90
Thrombocytopenia	21/115 (18.3%)	48	26/122 (21.3%)	69
Cardiac disorders
Tachycardia	10/115 (8.7%)	11	3/122 (2.5%)	3
Ear and labyrinth disorders
Vertigo	11/115 (9.6%)	13	12/122 (9.8%)	12
Tinnitus	8/115 (7%)	10	6/122 (4.9%)	7
Hearing impaired	6/115 (5.2%)	6	7/122 (5.7%)	8
Eye disorders
Conjunctivitis	10/115 (8.7%)	16	9/122 (7.4%)	12
Gastrointestinal disorders
Nausea	58/115 (50.4%)	122	63/122 (51.6%)	162
Diarrhoea	38/115 (33%)	73	41/122 (33.6%)	84
Vomiting	35/115 (30.4%)	67	41/122 (33.6%)	83
Constipation	34/115 (29.6%)	47	23/122 (18.9%)	40
Stomatitis	26/115 (22.6%)	66	12/122 (9.8%)	21
Dysphagia	15/115 (13%)	20	16/122 (13.1%)	22
Dyspepsia	15/115 (13%)	23	13/122 (10.7%)	19
Abdominal pain	7/115 (6.1%)	17	12/122 (9.8%)	13
Abdominal pain upper	9/115 (7.8%)	11	6/122 (4.9%)	6
General disorders
Fatigue	41/115 (35.7%)	82	38/122 (31.1%)	81
Asthenia	34/115 (29.6%)	60	37/122 (30.3%)	75
Mucosal inflammation	24/115 (20.9%)	45	36/122 (29.5%)	63
Pyrexia	16/115 (13.9%)	17	24/122 (19.7%)	30
Chills	26/115 (22.6%)	28	6/122 (4.9%)	6
General physical health deterioration	7/115 (6.1%)	10	6/122 (4.9%)	6
Infections and infestations
Paronychia	16/115 (13.9%)	36	12/122 (9.8%)	19
Pneumonia	13/115 (11.3%)	17	12/122 (9.8%)	14
Urinary tract infection	7/115 (6.1%)	12	6/122 (4.9%)	7
Bronchitis	3/115 (2.6%)	3	9/122 (7.4%)	14
Device related infection	8/115 (7%)	8	4/122 (3.3%)	5
Sepsis	4/115 (3.5%)	4	8/122 (6.6%)	8
Investigations
Weight decreased	42/115 (36.5%)	83	39/122 (32%)	72
Blood creatinine increased	11/115 (9.6%)	19	8/122 (6.6%)	15
Platelet count decreased	7/115 (6.1%)	13	6/122 (4.9%)	6
Metabolism and nutrition disorders
Hypomagnesaemia	53/115 (46.1%)	146	51/122 (41.8%)	181
Decreased appetite	36/115 (31.3%)	47	30/122 (24.6%)	48
Hypokalaemia	20/115 (17.4%)	35	22/122 (18%)	53
Dehydration	10/115 (8.7%)	11	13/122 (10.7%)	14
Hypocalcaemia	10/115 (8.7%)	19	13/122 (10.7%)	20
Hyponatraemia	11/115 (9.6%)	14	9/122 (7.4%)	9
Musculoskeletal and connective tissue disorders
Back pain	6/115 (5.2%)	9	7/122 (5.7%)	8
Nervous system disorders
Dizziness	14/115 (12.2%)	16	15/122 (12.3%)	20
Headache	13/115 (11.3%)	16	13/122 (10.7%)	19
Neuropathy periphera	3/115 (2.6%)	4	9/122 (7.4%)	19
Psychiatric disorders
Pulmonary embolism	8/115 (7%)	13	4/122 (3.3%)	5
Renal and urinary disorders
Renal failure	5/115 (4.3%)	7	11/122 (9%)	16
Respiratory, thoracic and mediastinal disorders
Cough	10/115 (8.7%)	10	15/122 (12.3%)	21
Dyspnoea	11/115 (9.6%)	17	14/122 (11.5%)	16
Epistaxis	6/115 (5.2%)	7	10/122 (8.2%)	13
Skin and subcutaneous tissue disorders
Rash	44/115 (38.3%)	116	47/122 (38.5%)	127
Dermatitis acneiform	30/115 (26.1%)	106	21/122 (17.2%)	64
Dry skin	20/115 (17.4%)	23	23/122 (18.9%)	26
Skin fissures	19/115 (16.5%)	38	17/122 (13.9%)	36
Acne	10/115 (8.7%)	23	11/122 (9%)	40
Alopecia	9/115 (7.8%)	10	11/122 (9%)	13
Erythema	8/115 (7%)	8	8/122 (6.6%)	10
Pruritus	10/115 (8.7%)	16	4/122 (3.3%)	6
Vascular disorders
Hypotension	16/115 (13.9%)	20	16/122 (13.1%)	24
Hypertension	11/115 (9.6%)	30	8/122 (6.6%)	13

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publication, presentation or use of the methods and/or results of the clinical trial are not permitted without prior written sponsor´s consent.