Zalutumumab in Non-curable Patients With SCCHN

• Sponsor: Genmab (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00542308
• Collaborator: (none)
• Enrollment: 90
• Locations: 48
• Arm: 1
• Duration (Months): 43
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Treatment, In combination with BSC, Open-label, Single arm, Efficacy Study.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Squamous Cell Cancer	Drug: Zalutumumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: An Open Label Single Arm Trial Investigating Zalutumumab, a Human Monoclonal Anti-EGF Receptor Antibody, in Combination With Best Supportive Care, in Patients With Non-Curable Squamous Cell Carcinoma of the Head and Neck Who Have Failed Standard Platinum-based Chemotherapy.
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zalutumumab 4-16 mg/kg Zalutumumab iv infusion once weekly. The dose was titrated until grade 2 rash occurred.	Drug: Zalutumumab; Individual dose titration weekly i.v. doses

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From randomization until death, assessed up to 21 months]

   Overall survival was defined as time from start of treatment until date of death of any cause.

Secondary Outcome Measures

1. Tumour Response [During treatment and two weeks after end of treatment, assessed up to 21 months.]

   Tumour response 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

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 prior chemotherapy regimens

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 of Alabama at Birmingham	Birmingham	Alabama	United States	35294-0012
2	Loma Linda University Cancer Institute	Loma Linda	California	United States	92354
3	Moffitt Cancer Center	Tampa	Florida	United States	33612
4	Mountain States Tumor Institute	Boise	Idaho	United States	83712
5	University Of Chicago Medical Center	Chicago	Illinois	United States	60637
6	Ft. Wayne Medical Oncology/Hematology, Inc	Ft. Wayne	Indiana	United States	46815
7	Henry Ford Health Systems	Detroit	Michigan	United States	48202
8	Oregon Health and Science University	Portland	Oregon	United States	97239
9	Baylor University Medical Center	Dallas	Texas	United States	75246
10	Medizinische Universität Graz	Graz		Austria	8036
11	Universitätsklinik für Innere Medizin III	Salzburg		Austria	5020
12	AKH Wien	Wien		Austria	1090
13	Instituto Clinico Oncologico del Sur ICOS	Temuco		Chile
14	Hospital Carlos Van Buren de Valparaiso	Valparaiso		Chile
15	Instituto Oncologico	Viña del Mar		Chile
16	Centro de Investigaciones Oncologicas Clinica CIO San Diego S.A	Bogota		Colombia
17	Hospital Pablo Tobon Uribe	Medellin		Colombia
18	Oncomedica S.A.	Montería		Colombia
19	Oncólogos del Occidente S.A.	Pereira		Colombia
20	Facultni Nemocnice Hradec Kralove	Hradec Králové		Czech Republic	500 05
21	Nemocnice Jihlava	Jihlava		Czech Republic	586 33
22	Veseobecna Fakultni Nemocnice	Prague		Czech Republic	128 08
23	Facultni Nemocnice Na Bulovce	Prague		Czech Republic	180 81
24	Universitätsklinikum Essen	Essen		Germany	45122
25	Klinikum der Johann Wolfgang Goethe Universität	Frankfurt am Main		Germany	60590
26	Uniklinik Freiburg	Freiburg		Germany	79106
27	Universitätsklinikum Heidelberg	Heidelberg		Germany	69120
28	Medizinische Universitätsklinik Lübeck	Lübeck		Germany	23538
29	Südharz-Krankenhaus Nordhausen gGmbH	Nordhausen		Germany	99734
30	Soroka Medical Center	Beer Sheva		Israel	84101
31	Rambam Medial Center	Haifa		Israel	31096
32	Shaare-Zedek Medical Center	Jerusalem		Israel	91031
33	Rabin Medical Center	Petah Tikva		Israel	49100
34	Sheba Medical Center	Ramat-Gan		Israel	52621
35	Sourasky Medical Center	Tel-Aviv		Israel	64239
36	Istituto Nazionale Tumori	Milan		Italy	20133
37	Istituto Europea di Oncologia	Milan		Italy	20141
38	Azienda Ospedaliera Valtellina e Valchiavenna	Sondrio		Italy	23100
39	Hospital Goyeneche	Arequipa		Peru
40	Hospital Nacional Carlos Alberto Seguin Escobedo	Arequipa		Peru
41	Hospital Nacional Almanzor Aguinaga Asenjo	Lambayeque		Peru
42	Hospital Central FAP	Lima		Peru
43	Hospital Nacional Guillermo Almenara Irigoyen	Lima		Peru
44	IPO Coimbra	Coimbra		Portugal	3000-075
45	IPO Lisboa	Lisboa		Portugal	1099-023
46	IPO Porto	Porto		Portugal	4200-072
47	Narodny onkologicky ustav	Bratislava		Slovakia	83310
48	FN Trnava	Trnava		Slovakia	917 75

Sponsors and Collaborators

• Genmab

Investigators

• Study Director: Steen Lisby, MD, Genmab A/S, Bredgade 34, DK-1260 Copenhagen K, Denmark

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genmab
• ClinicalTrials.gov Identifier: NCT00542308
• Other Study ID Numbers: GEN205
• First Posted: Oct 11, 2007
• Last Update Posted: Aug 27, 2014
• Last Verified: Jan 1, 2012

• Additional relevant MeSH terms: Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Zalutumumab

Study Results

Participant Flow

Pre-assignment Detail	All patients attending Visit 2 were included in the FAS irrespective of their compliance with the planned course of zalutumumab.

Arm/Group Title	Zalutumumab 4-16 mg/kg
Arm/Group Description	Zalutumumab iv infusion once weekly. The dose was titrated until grade 2 rash occurred.
Period Title: Overall Study
STARTED	90
COMPLETED	90
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Zalutumumab 4-16 mg/kg
Arm/Group Description	Zalutumumab iv infusion once weekly. The dose was titrated until grade 2 rash occurred.
Overall Participants	90
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	70 77.8%
>=65 years	20 22.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (8.7)
Sex: Female, Male (Count of Participants)
Female	18 20%
Male	72 80%
Region of Enrollment (participants) [Number]
Portugal	10 11.1%
United States	22 24.4%
Czech Republic	6 6.7%
Slovakia	4 4.4%
Peru	4 4.4%
Austria	3 3.3%
Israel	12 13.3%
Chile	8 8.9%
Germany	11 12.2%
Colombia	1 1.1%
Italy	9 10%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival was defined as time from start of treatment until date of death of any cause.
Time Frame	From randomization until death, assessed up to 21 months

Outcome Measure Data

Analysis Population Description

All patients attending Visit 2 were included in the full analysis set irrespective of their compliance with the planned course of zalutumumab.

Arm/Group Title	Zalutumumab 4-16 mg/kg
Arm/Group Description	Zalutumumab iv infusion once weekly. The dose was titrated until grade 2 rash occurred.
Measure Participants	90
Median (95% Confidence Interval) [months]	5.3

2. Secondary Outcome

Title	Tumour Response
Description	Tumour response 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	During treatment and two weeks after end of treatment, assessed up to 21 months.

Outcome Measure Data

Analysis Population Description

All patients attending Visit 2 were included in the full analysis set irrespective of their compliance with the planned course of zalutumumab.

Arm/Group Title	Zalutumumab 4-16 mg/kg
Arm/Group Description	Zalutumumab iv infusion once weekly. The dose was titrated until grade 2 rash occurred.
Measure Participants	90
Complete response	1 1.1%
Partial response	4 4.4%
Stable response	30 33.3%
Progressive disease	33 36.7%
Not evaluable	20 22.2%

Adverse Events

Time Frame	Adverse events were collected at weekly visits until disease progression, intercurrent illness preventing further administration, unacceptable toxicity, or patient decision.
Arm/Group Title	Zalutumumab 4-16 mg/kg
Arm/Group Description	Zalutumumab iv infusion once weekly. The dose was titrated until grade 2 rash occurred.
All Cause Mortality
	Zalutumumab 4-16 mg/kg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Zalutumumab 4-16 mg/kg
	Affected / at Risk (%)	# Events
Total	83/90 (92.2%)
Gastrointestinal disorders
Gastrointestinal disorders	8/90 (8.9%)	9
Dysphagia	5/90 (5.6%)	6
General disorders
General disorders and administration site conditions	61/90 (67.8%)	64
Disease progression	55/90 (61.1%)	55
Infections and infestations
Infections and infestations	16/90 (17.8%)	19
Pneumonia	7/90 (7.8%)	8
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	9/90 (10%)	9
Tumor hemorrhage	6/90 (6.7%)	6
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	17/90 (18.9%)	22
Dyspnea	9/90 (10%)	9
Other (Not Including Serious) Adverse Events
	Zalutumumab 4-16 mg/kg
	Affected / at Risk (%)	# Events
Total	90/90 (100%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	13/90 (14.4%)	16
Eye disorders
Eye disorders	10/90 (11.1%)	12
Gastrointestinal disorders
Gastrointestinal disorders	49/90 (54.4%)	131
General disorders
General disorders and administration site conditions	77/90 (85.6%)	210
Infections and infestations
Infections and infestations	49/90 (54.4%)	100
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	13/90 (14.4%)	19
Investigations
Investigations	22/90 (24.4%)	46
Metabolism and nutrition disorders
Metabolism and nutrition disorders	40/90 (44.4%)	72
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	29/90 (32.2%)	40
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	21/90 (23.3%)	28
Nervous system disorders
Nervous system disorders	28/90 (31.1%)	46
Psychiatric disorders
Psychiatric disorders	19/90 (21.1%)	22
Renal and urinary disorders
Renal and urinary disorders	11/90 (12.2%)	13
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	42/90 (46.7%)	75
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	72/90 (80%)	138
Vascular disorders
Vascular disorders	14/90 (15.6%)	17

Limitations/Caveats

This was an uncontrolled single-arm open-label trial with no formal statistical tests planned.

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.