Zalutumumab in Patients With Non-curable Head and Neck Cancer

• Sponsor: Genmab (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00382031
• Collaborator: (none)
• Enrollment: 286
• Locations: 82
• Arms: 2
• Duration (Months): 57
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate if zalutumumab in combination with Best Supportive Care (BSC) is superior to BSC in non-curable patients with head and neck cancer

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Squamous Cell Cancer	Drug: Zalutumumab; Other: Control	Phase 3

Detailed Description

This is an open parallel group trial. Patients will be randomized in a 2:1 manner to receive either treatment with zalutumumab in combination with Best Supportive Care (BSC) or BSC.

Patients randomized to treatment with zalutumumab in combination with BSC will receive weekly infusions with zalutumumab starting with a loading dose (8mg/kg) followed by weekly maintenance doses until disease progression, intercurrent illness preventing further administration, unacceptable toxicity or patient decision. After Visit 2 the patient should be evaluated for presence of skin rash prior to each infusion to allow dose titration.

Individual dose titration until the patient develops grade 2 skin rash will be applied. The maximum dose used in study will be 16 mg/kg.

Study Design

• Study Type: Interventional
• Actual Enrollment: 286 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Labeled Randomized Parallel Group Trial of Zalutumumab, a Human Monoclonal Anti-EGFr Antibody, in Combination With Best Supportive Care (BSC) vs BSC, in Pts With Non-Curable SCCHN Who Have Failed Standard Platinum-Based Chemotherapy
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: zalutumumab Zalutumumab in combination with Best Supportive Care	Drug: Zalutumumab; Individual dose titration weekly i.v doses; Other Names: Zalutumumab in combination with Best Supportive Care ; Other: Control; Best Supportive Care; Other Names: Best Supportive Care
Other: Control Best Supportive Care	Other: Control; Best Supportive Care; Other Names: Best Supportive Care

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From randomization until death]

   A patient's overall survival was defined as the time from the date of randomization until the date of death from any cause, assessed up to 41 months. Overall survival was censored if the patient was lost to follow-up or refused to continue in the trial.

Secondary Outcome Measures

1. Objective Tumor Response [From date of randomization until the date of death from any cause, assessed up to 41 months.]

   Objective tumor response assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v 1.0) J Natl Cancer Inst 2000;92:205-16 assessed by CT/MRI. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the longest diameter of target lesions; Overall Response (OR), CR+PR

2. Duration of Response [Time from complete or partial response until death, recurrence or progressive disease, assessed up to 41 months.]

   Duration of response defined as the time from the first date where measurement criteria for complete or partial response (whichever status is recorded first) are met until the first date that death, recurrence or progressive disease is objectively documented.

3. Progression Free Survival (PFS) [From randomization until disease progression or death, assessed up to 41 months.]

   PFS (defined as the time from randomization until disease progression or death). The progression events were defined by well-documented and verifiable imaging data. In case of censoring, the date of censoring had to be the last time point documenting the status of the patient.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Males and Females age ≥ 18 years

2. Confirmed diagnosis, initially or at relapse, of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, considered incurable with standard therapy

3. Failure to at least one course of standard platinum-based chemotherapy

Exclusion Criteria:

1. Three or more chemotherapy regimens other than platinum-based chemotherapy

2. Prior treatment with EGFr antibodies and/or EGFr small molecule inhibitors

3. Past or current malignancy other than SCCHN, except for certain other cancer diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Antwerp	Antwerp		Belgium
2	St-Luc University Hospital	Brussels		Belgium
3	CHNDRF	Charleroi		Belgium
4	"University Hospital	Gent		Belgium
5	University Hospital Leuven	Leuven		Belgium
6	Cliniques Saint Pierre	Ottignies		Belgium
7	BioCancer	Belo Horizonte		Brazil
8	Hospital Erasto Gaertner	Curitiba		Brazil
9	Centro Goiano de Oncologia	Goiânia		Brazil
10	Hospital Araújo Jorge	Goiânia		Brazil
11	Fundação Amaral Carvalho	Jaú		Brazil
12	CliniOnco	Porto Alegre		Brazil
13	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil
14	Cepho - Centro de Estudos e pesquisa em Hematologia e Oncologia	Santo André		Brazil
15	Santo Andre Diag e Tratamentos	Santo André		Brazil
16	UNIFESP	São Paulo - SP		Brazil
17	Centro de Oncologia - InRad HCFMUSP	São Paulo		Brazil
18	Hospital Heliópolis	São Paulo		Brazil
19	IBCC - Instituto Brasileiro de Combate ao Câncer	São Paulo		Brazil
20	Tom Baker Cancer Centre	Calgary	Alberta	Canada
21	Cross Cancer Institute	Edmonton	Alberta	Canada
22	London Regional Cancer Program	London	Ontario	Canada
23	Princess Margaret Hospital	Toronto	Ontario	Canada
24	BC Cancer Agency	Vancouver, British Colombia		Canada
25	North-Estonian Regional Hospital	Tallinn		Estonia
26	Hôpital Beaujon- department of medical oncology	Clichy		France
27	Centre Oscar Lambrette	Lille Cedex		France
28	Centre Antoine Lacassagne	Nice		France
29	Hôpital Tenon - department of medical oncology	Paris Cedex		France
30	Institut Gustave Roussy	Villejuif Cedex		France
31	Semmelweis University	Budapest		Hungary
32	Uzsoki Hospital Budapest	Budapest		Hungary
33	University of Debrecen	Debrecen		Hungary
34	Petz Aladár	Gyor		Hungary
35	Szabolcs-Szatmar-Bereg County Hospital	Nyiregyhaza		Hungary
36	University of Szeged	Szeged		Hungary
37	Markusovszky County Hospital	Szombathely		Hungary
38	Szent Borbála County Hospital Oncology Department	Tatabánya		Hungary
39	Zala County Hospital	Zalaegerszeg-Pózca		Hungary
40	Klaipeda Hospital	Klaipeda		Lithuania
41	Vilnius University	Vilnius		Lithuania
42	Beskidzkie Centrum Onkologii	Bielsko-Biala		Poland
43	Samodzielny Publiczny Szpital Kiniczny Nr1	Gdansk		Poland
44	Katedra i Onkologii Collegium	Krakow		Poland
45	Szpital Specjalistyczny im. Rydygiera	Krakow		Poland
46	Centrum Onkologii	Lublin		Poland
47	Zakład Opieki Zdrowotnej MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn		Poland
48	Centrum Onkologii - Instytut im. M. Curie-Skłodowskiej	Warszawa		Poland
49	Dolnoslaskie Centrum Onkologii	Wroclaw		Poland
50	Szpital Wojewódzki SP ZOZ	Zielona Góra		Poland
51	Belgorod Regional Oncology Dispensary	Belgorod		Russian Federation
52	Regional Oncology Dispensary	Chelyabinsk		Russian Federation
53	Republican Clinical Oncology Dispensary	Izhevsk		Russian Federation
54	Kursk Regional Oncology Dispencary	Kursk		Russian Federation
55	Kursk Regional Oncology Dispensary	Kursk		Russian Federation
56	City Clinincal Oncology Dispensary #1	Moscow		Russian Federation
57	Moscow Research Institute of Oncology	Moscow		Russian Federation
58	NUZ Semashko Central Clinical Hospital No2 OAO	Moscow		Russian Federation
59	Russian Oncology Research Center n.a. Blokhin	Moscow		Russian Federation
60	GUZ NO Oncology Dispensary	Nizhiy Novgorod		Russian Federation
61	Medical Radiological Research Center	Obninsk		Russian Federation
62	Sochi Oncology Center	Sochi		Russian Federation
63	St. Petersburg State Medical University	St. Petersburg		Russian Federation
64	Stavropol Regional Clinical Oncology Dispensary	Stavropol		Russian Federation
65	Tula Region Oncology Dispensary	Tula		Russian Federation
66	GUZ Volgograd Region Clinical Oncology Dispensary No1	Volgograd		Russian Federation
67	Voronezh Region Clinical Oncology Dispensary	Voronezh		Russian Federation
68	Institute for Oncology and Radiology	Belgrade		Serbia
69	Military Medical Academy	Belgrade		Serbia
70	Institute of Oncology Sremska Kamenica	Kamenica		Serbia
71	Clinic of Maxillofacial Surgery Nis	Nis		Serbia
72	Sahlgrenska University Hospital	Göteborg		Sweden
73	Lund University Hospital	Lund		Sweden
74	Musgrove Park Hospital	Taunton	Somerset	United Kingdom
75	Royal Surrey County	Guildford	Surrey	United Kingdom
76	Bristol Haematology and Oncology Centre	Bristol		United Kingdom
77	The Beatson West of Scotland Centre	Glasgow		United Kingdom
78	Royal Marsden Hospital	London		United Kingdom
79	Christie Hospital	Manchester		United Kingdom
80	Newcastle General Hospital	Newcastle		United Kingdom
81	Weston Park Hospital	Sheffield		United Kingdom
82	New Cross Hospital	Wolverhampton		United Kingdom

Sponsors and Collaborators

• Genmab

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genmab
• ClinicalTrials.gov Identifier: NCT00382031
• Other Study ID Numbers: Hx-EGFr-202
• First Posted: Sep 28, 2006
• Last Update Posted: Oct 15, 2013
• Last Verified: Aug 1, 2013

• Additional relevant MeSH terms: Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Zalutumumab; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Zalutumumab	Control
Arm/Group Description	Zalutumumab in combination with Best Supportive Care. Patients received weekly infusions of zalutumumab. After a loading dose of 8 mg/kg the dose was reduced to 4 mg/kg and individual dose titration based on skin rash evaluation was performed.	Best Supportive Care
Period Title: Overall Study
STARTED	191	95
COMPLETED	191	95
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Zalutumumab	Control	Total
Arm/Group Description	Zalutumumab in combination with Best Supportive Care	Best Supportive Care	Total of all reporting groups
Overall Participants	191	95	286
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	161 84.3%	77 81.1%	238 83.2%
>=65 years	30 15.7%	18 18.9%	48 16.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (9)	57 (9)	57 (9)
Sex: Female, Male (Count of Participants)
Female	22 11.5%	12 12.6%	34 11.9%
Male	169 88.5%	83 87.4%	252 88.1%
Region of Enrollment (participants) [Number]
Serbia	5 2.6%	1 1.1%	6 2.1%
Estonia	3 1.6%	1 1.1%	4 1.4%
Spain	1 0.5%	4 4.2%	5 1.7%
Lithuania	2 1%	0 0%	2 0.7%
Russian Federation	42 22%	22 23.2%	64 22.4%
United Kingdom	22 11.5%	10 10.5%	32 11.2%
France	13 6.8%	3 3.2%	16 5.6%
Hungary	37 19.4%	20 21.1%	57 19.9%
Canada	10 5.2%	8 8.4%	18 6.3%
Brazil	7 3.7%	4 4.2%	11 3.8%
Belgium	31 16.2%	20 21.1%	51 17.8%
Poland	14 7.3%	2 2.1%	16 5.6%
Sweden	4 2.1%	0 0%	4 1.4%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	A patient's overall survival was defined as the time from the date of randomization until the date of death from any cause, assessed up to 41 months. Overall survival was censored if the patient was lost to follow-up or refused to continue in the trial.
Time Frame	From randomization until death

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.

Arm/Group Title	Zalutumumab	Control
Arm/Group Description	Zalutumumab in combination with Best Supportive Care	Best Supportive Care
Measure Participants	191	95
Median (95% Confidence Interval) [months]	6.7	5.2

2. Secondary Outcome

Title	Objective Tumor Response
Description	Objective tumor response assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v 1.0) J Natl Cancer Inst 2000;92:205-16 assessed by CT/MRI. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the longest diameter of target lesions; Overall Response (OR), CR+PR
Time Frame	From date of randomization until the date of death from any cause, assessed up to 41 months.

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.

Arm/Group Title	Zalutumumab	Control
Arm/Group Description	Zalutumumab in combination with Best Supportive Care	Best Supportive Care
Measure Participants	191	95
Complete response	2 1%	0 0%
Partial response	10 5.2%	1 1.1%
Stable disease	79 41.4%	25 26.3%
Progressive disease	70 36.6%	38 40%
Not evaluable	30 15.7%	31 32.6%

3. Secondary Outcome

Title	Duration of Response
Description	Duration of response defined as the time from the first date where measurement criteria for complete or partial response (whichever status is recorded first) are met until the first date that death, recurrence or progressive disease is objectively documented.
Time Frame	Time from complete or partial response until death, recurrence or progressive disease, assessed up to 41 months.

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.

Arm/Group Title	Zalutumumab	Control
Arm/Group Description	Zalutumumab in combination with Best Supportive Care	Best Supportive Care
Measure Participants	12	1
Median (95% Confidence Interval) [month]	5.5	7.4

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS (defined as the time from randomization until disease progression or death). The progression events were defined by well-documented and verifiable imaging data. In case of censoring, the date of censoring had to be the last time point documenting the status of the patient.
Time Frame	From randomization until disease progression or death, assessed up to 41 months.

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.

Arm/Group Title	Zalutumumab	Control
Arm/Group Description	Zalutumumab in combination with Best Supportive Care	Best Supportive Care
Measure Participants	191	95
Median (95% Confidence Interval) [weeks]	9.9	8.4

Adverse Events

Time Frame	Adverse events were collected during weekly visits for patients treated with zalutumumab and visits every fourth week for patients randomized to the control group.
Adverse Event Reporting Description	The safety analysis population included all 283 patients who had attended Visit 2.
Arm/Group Title	Zalutumumab		Control
Arm/Group Description	Zalutumumab in combination with Best Supportive Care		Best Supportive Care
All Cause Mortality
	Zalutumumab		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Zalutumumab		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	180/189 (95.2%)		87/94 (92.6%)
Gastrointestinal disorders
Gastrointestinal disorders	19/189 (10.1%)	20	3/94 (3.2%)	3
Dysphagia	10/189 (5.3%)	10	2/94 (2.1%)	2
General disorders
General disorders and administration site conditions	127/189 (67.2%)	138	63/94 (67%)	64
Disease progression	118/189 (62.4%)	118	60/94 (63.8%)	60
Infections and infestations
Infections and Infestations	35/189 (18.5%)	46	11/94 (11.7%)	11
Pneumonia	14/189 (7.4%)	15	3/94 (3.2%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	38/189 (20.1%)	48	22/94 (23.4%)	27
Tumour hemorrhage	32/189 (16.9%)	41	14/94 (14.9%)	17
Other (Not Including Serious) Adverse Events
	Zalutumumab		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	188/189 (99.5%)		92/94 (97.9%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	66/189 (34.9%)	121	26/94 (27.7%)	44
Eye disorders
Eye disorders	24/189 (12.7%)	37	5/94 (5.3%)	5
Gastrointestinal disorders
Gastrointestinal disorders	102/189 (54%)	298	43/94 (45.7%)	119
General disorders
General disorders and administration site conditions	159/189 (84.1%)	359	78/94 (83%)	161
Infections and infestations
Infections and Infestations	79/189 (41.8%)	171	29/94 (30.9%)	35
Investigations
Investigations	56/189 (29.6%)	77	12/94 (12.8%)	14
Metabolism and nutrition disorders
Metabolism and nutrition disorders	77/189 (40.7%)	150	20/94 (21.3%)	27
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	46/189 (24.3%)	78	27/94 (28.7%)	41
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	50/189 (26.5%)	75	30/94 (31.9%)	39
Nervous system disorders
Nervous system disorders	70/189 (37%)	114	22/94 (23.4%)	38
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	80/189 (42.3%)	177	33/94 (35.1%)	51
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	174/189 (92.1%)	355	10/94 (10.6%)	13
Vascular disorders
Vascular disorders	28/189 (14.8%)	38	7/94 (7.4%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The site and the PI may be required to withhold the publication for up to 90 days. Subject to a reasoned request from the sponsor, the publication may be further delayed for a period up to 6 months from the date of first submission to the sponsor. The sponsor has the right to require deletion of any trade secret, proprietary, or confidential information supplied by the sponsor to the site or the PI. The sponsor shall not otherwise have the right to censor publications.