Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02633800
• Collaborator: (none)
• Enrollment: 87
• Locations: 34
• Arms: 2
• Actual Duration (Months): 26
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will test an investigational study drug called patritumab. It is a 'randomized study' which means participants have an equal chance of being assigned to receive the experimental medication (patritumab) or a substance that looks like the experimental product, but is not (placebo). Patritumab may work when combined with other medications that are approved for the treatment of head and neck cancer. They are called cetuximab, cisplatin or carboplatin. All participants will receive the other medications approved for treatment of head and neck cancer, even if they do not receive the experimental product.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Neoplasms	Drug: Patritumab; Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin; Drug: Placebo	Phase 2

Detailed Description

Main objective of the trial:

The main objective of the trial is to evaluate progression-free survival (PFS) in the heregulin (HRG) high expression population from subjects treated with patritumab + cetuximab

• platinum-based therapy compared to placebo + cetuximab + platinum-based therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Placebo-controlled, Double-blind Phase 2 Study of Patritumab (U3-1287) in Combination With Cetuximab Plus Platinum-based Therapy in First Line Setting in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
• Actual Study Start Date: Dec 22, 2015
• Actual Primary Completion Date: Jan 11, 2018
• Actual Study Completion Date: Feb 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patritumab All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Drug: Patritumab; Patritumab initial loading dose is 18 mg/kg IV over 60 minutes followed by a maintenance dose of 9 mg/kg IV over 60 minutes (± 10 minutes) every three weeks; Other Names: U3-1287 ; Drug: Cetuximab; Cetuximab 400 mg/mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly; Drug: Cisplatin; Cisplatin at 100 mg/m^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles; Other Names: Platinum-based therapy ; Drug: Carboplatin; Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles; Other Names: Platinum-based therapy
Placebo Comparator: Placebo All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Drug: Cetuximab; Cetuximab 400 mg/mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly; Drug: Cisplatin; Cisplatin at 100 mg/m^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles; Other Names: Platinum-based therapy ; Drug: Carboplatin; Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles; Other Names: Platinum-based therapy ; Drug: Placebo; Placebo to match patritumab

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population [from Day 0 to end of active study (study termination) - within 12 months]

   PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first. Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method.

Secondary Outcome Measures

1. Median Overall Survival [at approximately 25 months]

   Overall survival (OS) is defined as the time from the date of randomization to death due to any cause

2. Percentage of Participants With Best Overall Response [at approximately 22 months]

   Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Has histologically confirmed recurrent disease or metastatic SCCHN tumor and/or from its lymph nodal metastases originating from the oral cavity, oropharynx, hypopharynx, and larynx

• Has or be willing to provide tumor tissue for testing

• Has measurable disease per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1

• Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Has adequate hematological function per protocol

• Has adequate renal function per protocol

• Has adequate hepatic function per protocol

• Agrees to use effective contraception while on the study and for 6-months after the end of the study

• Provides written informed consent(s)

Exclusion Criteria:

• Has left ventricular ejection fraction (LVEF) <50%

• Had prior epidermal growth factor receptor (EGFR) targeted regimen

• Had prior anti-human epidermal growth factor receptor 3 (anti-HER3) therapy

• Had prior chemotherapy for recurrent/metastatic disease

• Had anti-cancer therapy between biopsy and submission of sample

• Has history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years

• Has known history of brain metastases or active brain metastases

• Has uncontrolled hypertension

• Has clinically significant electrocardiograph (ECG) findings

• Had myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or arrhythmia requiring medication

• Had platinum-containing drug therapy with radiotherapy less than 6 months before study drug treatment

• Had therapeutic or palliative radiation therapy or major surgery within 4 weeks before study drug treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut Jules Bordet	Brussels		Belgium	1000
2	Univeristair Ziekenhuis Antwerpen	Edegem		Belgium	2650
3	UZ Leuven	Leuven		Belgium	3000
4	Institut Curie	Paris	Cedex	France	75248
5	Institut de Cancerologie de l'Ouest	Angers cedex 02		France	49055
6	Centre Hospitalier de Bordeaux - Hôpital Saint André	Bordeaux		France	33075
7	Hopital Croix-Rousse	Lyon		France	69004
8	Centre Leon Berard	Lyon		France	69373
9	CHU Hopital de la Timone	Marseille		France	13005
10	Hopital Saint Joseph	Marseille		France	13008
11	Centre de Cancerologie du Grand Montpellier	Montpellier		France	34070
12	Institut de Cancerologie de l'Ouest	Saint-Herblain Cedex		France	44805
13	Gustave Roussy	Villejuif		France	94805
14	Charite Universitatsmedizin Berlin	Berlin		Germany	12200/12203
15	Medizinische Hochschule Hannover	Hannover		Germany	30625
16	Klinikum der Universitat Munchen	München		Germany	81377
17	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
18	Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum	Debrecen		Hungary	4032
19	Bacs-Kiskun Megyei Korhaz	Kecskemet		Hungary	6000
20	Borsod Abauj Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc		Hungary	3526
21	Josa Andras Oktatokorhaz	Nyíregyháza		Hungary	4400
22	Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy	Bydgoszcz		Poland	85-796
23	Przychodnia Lekarska "KOMED"	Konin		Poland	62-500
24	Regionalny Osrodek Onkologiczny Szpital im. M. Kopernika w Lodzi	Lodz		Poland	93-513
25	Medisprof SRL	Cluj-Napoca		Romania	400058
26	Centrul de Oncologie Sfantul Nectarie	Craiova		Romania	200347
27	Institutul Regional de Oncologie Iasi	Iasi		Romania	700483
28	University College London Hospitals NHS Foundation Trust - University College Hospital	London		United Kingdom	NW1 2PG
29	Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital	London		United Kingdom	SE1 7EH
30	The Royal Marsden NHS Foundation Trust	London		United Kingdom	SW3 6JJ
31	Weston Park Hospital	Sheffield		United Kingdom	S10 2SJ
32	The Shrewsbury and Telford Hospital NHS Trust	Shrewsbury		United Kingdom	SY3 8XQ
33	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
34	The Royal Marsden NHS Foundation Trust	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

• Principal Investigator: Kevin Harrington, Prof, MD, Royal Marsden NHS Foundation Trust

Study Documents (Full-Text)

• Study Protocol - Jun 14, 2016
• Statistical Analysis Plan - Nov 29, 2016

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT02633800
• Other Study ID Numbers: U31287-A-U203; 2015-002222-40
• First Posted: Dec 17, 2015
• Last Update Posted: Jan 7, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Daiichi Sankyo, Inc.: Squamous cell cancer of the head and neck; Squamous cell carcinoma; Head and neck cancer; Neoplasms by site
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carboplatin; Cetuximab

Study Results

Participant Flow

Pre-assignment Detail	Of 125 screened, 87 patients from 8 countries were randomized into treatment groups

Arm/Group Title	Patritumab	Placebo
Arm/Group Description	All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Period Title: Overall Study
STARTED	44	43
COMPLETED	0	0
NOT COMPLETED	44	43

Baseline Characteristics

Arm/Group Title	Patritumab	Placebo	Total
Arm/Group Description	All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Total of all reporting groups
Overall Participants	44	43	87
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (9.18)	61.0 (9.19)	59.1 (9.33)
Age, Customized (Count of Participants)
18-64 Years	32 72.7%	27 62.8%	59 67.8%
65-84 Years	12 27.3%	16 37.2%	28 32.2%
Sex: Female, Male (Count of Participants)
Female	8 18.2%	7 16.3%	15 17.2%
Male	36 81.8%	36 83.7%	72 82.8%
Race/Ethnicity, Customized (Count of Participants)
White	37 84.1%	37 86%	74 85.1%
Asian	1 2.3%	0 0%	1 1.1%
Other, Not Specified	6 13.6%	6 14%	12 13.8%
Region of Enrollment (Count of Participants)
Romania	1 2.3%	3 7%	4 4.6%
Belgium	1 2.3%	1 2.3%	2 2.3%
Hungary	20 45.5%	19 44.2%	39 44.8%
Poland	3 6.8%	2 4.7%	5 5.7%
United Kingdom	9 20.5%	5 11.6%	14 16.1%
France	9 20.5%	12 27.9%	21 24.1%
Germany	1 2.3%	1 2.3%	2 2.3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0=Fully active	19 43.2%	22 51.2%	41 47.1%
1=Restricted in Physically Strenuous Activity	25 56.8%	20 46.5%	45 51.7%
2=Ambulatory and Capable of All Self-Care	0 0%	1 2.3%	1 1.1%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population
Description	PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first. Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method.
Time Frame	from Day 0 to end of active study (study termination) - within 12 months

Outcome Measure Data

Analysis Population Description

Participants in the heregulin-high expression population

Arm/Group Title	Patritumab	Placebo
Arm/Group Description	All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Measure Participants	26	25
Median (95% Confidence Interval) [months]	5.56	5.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patritumab, Placebo
	Comments	Heregulin-high population - Patritumab vs Placebo
	Type of Statistical Test	Other
	Comments	Both Log-rank test and Cox regression analysis did not adjust stratification factors.
Statistical Test of Hypothesis	p-Value	0.8342
	Comments	Unstratified Log-rank p-value
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9291
	Confidence Interval	(2-Sided) 95%; 0.4856 to 1.7778
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Median Overall Survival
Description	Overall survival (OS) is defined as the time from the date of randomization to death due to any cause
Time Frame	at approximately 25 months

Outcome Measure Data

Analysis Population Description

The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).

Arm/Group Title	Patritumab	Placebo
Arm/Group Description	All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Measure Participants	0	0

3. Secondary Outcome

Title	Percentage of Participants With Best Overall Response
Description	Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR)
Time Frame	at approximately 22 months

Outcome Measure Data

Analysis Population Description

The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).

Arm/Group Title	Patritumab	Placebo
Arm/Group Description	All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were collected until trial termination at 12 months.
Arm/Group Title	Patritumab		Placebo
Arm/Group Description	All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)		All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
All Cause Mortality
	Patritumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/44 (54.5%)		20/43 (46.5%)
Serious Adverse Events
	Patritumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/44 (43.2%)		16/43 (37.2%)
Blood and lymphatic system disorders
Anaemia	0/44 (0%)	0	1/43 (2.3%)	1
Febrile neutropenia	1/44 (2.3%)	1	0/43 (0%)	0
Cardiac disorders
Acute Coronary Syndrome	0/44 (0%)	0	1/43 (2.3%)	1
Arrhythmia	1/44 (2.3%)	1	0/43 (0%)	0
Cardiac Disorder	0/44 (0%)	0	1/43 (2.3%)	1
Cardio-respiratory arrest	0/44 (0%)	0	1/43 (2.3%)	1
Cardiovascular insufficiency	1/44 (2.3%)	1	1/43 (2.3%)	1
Myocardial ischaemia	1/44 (2.3%)	1	0/43 (0%)	0
Sinus tachycardia	1/44 (2.3%)	1	0/43 (0%)	0
Ear and labyrinth disorders
Vertigo	1/44 (2.3%)	1	0/43 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/44 (2.3%)	1	0/43 (0%)	0
Diarrhoea	0/44 (0%)	0	1/43 (2.3%)	2
Dysphagia	1/44 (2.3%)	1	0/43 (0%)	0
Melaena	1/44 (2.3%)	1	0/43 (0%)	0
Nausea	0/44 (0%)	0	1/43 (2.3%)	1
Oral pain	1/44 (2.3%)	1	0/43 (0%)	0
Pancreatitis acute	0/44 (0%)	0	1/43 (2.3%)	1
General disorders
Asthenia	0/44 (0%)	0	1/43 (2.3%)	1
General physical health deterioration	0/44 (0%)	0	1/43 (2.3%)	2
Localised oedema	1/44 (2.3%)	1	0/43 (0%)	0
Non-cardiac chest pain	1/44 (2.3%)	1	0/43 (0%)	0
Malaise	0/44 (0%)	0	1/43 (2.3%)	1
Immune system disorders
Anaphylactic shock	0/44 (0%)	0	1/43 (2.3%)	1
Hypersensitivity	1/44 (2.3%)	1	0/43 (0%)	0
Infections and infestations
Arthritis bacterial	1/44 (2.3%)	1	0/43 (0%)	0
Catheter site infection	1/44 (2.3%)	1	0/43 (0%)	0
Device related infection	2/44 (4.5%)	2	0/43 (0%)	0
Empyema	1/44 (2.3%)	1	0/43 (0%)	0
Gastroenteritis	0/44 (0%)	0	1/43 (2.3%)	1
Lymphangitis	1/44 (2.3%)	1	0/43 (0%)	0
Pneumonia	4/44 (9.1%)	7	0/43 (0%)	0
Sepsis	0/44 (0%)	0	2/43 (4.7%)	2
Injury, poisoning and procedural complications
Fall	0/44 (0%)	0	1/43 (2.3%)	1
Head Injury	0/44 (0%)	0	1/43 (2.3%)	1
Investigations
Ejection Fraction Decreased	1/44 (2.3%)	1	0/43 (0%)	0
Neutrophil count decreased	0/44 (0%)	0	1/43 (2.3%)	1
Weight decreased	1/44 (2.3%)	1	0/43 (0%)	0
Metabolism and nutrition disorders
Cachexia	0/44 (0%)	0	1/43 (2.3%)	1
Decreased Appetite	0/44 (0%)	0	1/43 (2.3%)	1
Dehydration	3/44 (6.8%)	4	2/43 (4.7%)	2
Hypercalcaemia	0/44 (0%)	0	1/43 (2.3%)	1
Hypokalaemia	1/44 (2.3%)	1	0/43 (0%)	0
Hyponatraemia	1/44 (2.3%)	1	0/43 (0%)	0
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/44 (2.3%)	1	0/43 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	1/44 (2.3%)	1	0/43 (0%)	0
Tumour haemorrhage	0/44 (0%)	0	4/43 (9.3%)	4
Tumour pain	2/44 (4.5%)	2	0/43 (0%)	0
Nervous system disorders
Dizziness	1/44 (2.3%)	1	0/43 (0%)	0
Loss of consciousness	0/44 (0%)	0	1/43 (2.3%)	1
Syncope	0/44 (0%)	0	1/43 (2.3%)	1
Renal and urinary disorders
Renal failure	0/44 (0%)	0	1/43 (2.3%)	1
Renal Impairment	1/44 (2.3%)	1	0/43 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acquired tracheo-oesophageal fistula	1/44 (2.3%)	1	0/43 (0%)	0
Dyspnoea	1/44 (2.3%)	1	0/43 (0%)	0
Hypoxia	0/44 (0%)	0	1/43 (2.3%)	1
Lower respiratory tract congestion	0/44 (0%)	0	1/43 (2.3%)	1
Pneumonia aspiration	1/44 (2.3%)	1	0/43 (0%)	0
Pneumothorax	1/44 (2.3%)	1	0/43 (0%)	0
Pulmonary Embolism	0/44 (0%)	0	1/43 (2.3%)	1
Respiratory distress	1/44 (2.3%)	1	0/43 (0%)	0
Other (Not Including Serious) Adverse Events
	Patritumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/44 (100%)		42/43 (97.7%)
Blood and lymphatic system disorders
Anaemia	18/44 (40.9%)	34	13/43 (30.2%)	22
Leukocytosis	5/44 (11.4%)	5	0/43 (0%)	0
Neutropenia	13/44 (29.5%)	23	11/43 (25.6%)	22
Thrombocytopenia	10/44 (22.7%)	20	14/43 (32.6%)	39
Cardiac disorders
Tachycardia	3/44 (6.8%)	5	0/43 (0%)	0
Ear and labyrinth disorders
Tinnitus	4/44 (9.1%)	4	2/43 (4.7%)	2
Gastrointestinal disorders
Constipation	7/44 (15.9%)	7	5/43 (11.6%)	7
Diarrhoea	12/44 (27.3%)	18	5/43 (11.6%)	6
Dysphagia	8/44 (18.2%)	10	4/43 (9.3%)	4
Gastrooesophageal Reflux Disease	4/44 (9.1%)	4	2/43 (4.7%)	2
Nausea	16/44 (36.4%)	23	14/43 (32.6%)	22
Oral Pain	3/44 (6.8%)	3	1/43 (2.3%)	1
Stomatitis	5/44 (11.4%)	9	3/43 (7%)	3
Vomiting	9/44 (20.5%)	11	7/43 (16.3%)	14
General disorders
Asthenia	10/44 (22.7%)	14	11/43 (25.6%)	17
Chills	4/44 (9.1%)	5	2/43 (4.7%)	2
Fatigue	11/44 (25%)	14	7/43 (16.3%)	9
Mucosal inflammation	8/44 (18.2%)	13	2/43 (4.7%)	2
Oedema peripheral	1/44 (2.3%)	1	3/43 (7%)	3
Pyrexia	4/44 (9.1%)	7	1/43 (2.3%)	1
Infections and infestations
Conjunctivitis	6/44 (13.6%)	6	4/43 (9.3%)	5
Folliculitis	2/44 (4.5%)	3	5/43 (11.6%)	6
Paronychia	15/44 (34.1%)	25	4/43 (9.3%)	4
Investigations
Alanine aminotransferase increased	3/44 (6.8%)	6	2/43 (4.7%)	2
Aspartate aminotransferase increased	3/44 (6.8%)	5	1/43 (2.3%)	1
Blood alkaline phosphatase increased	3/44 (6.8%)	6	0/43 (0%)	0
Neutrophil count decreased	0/44 (0%)	0	3/43 (7%)	4
Weight Decreased	11/44 (25%)	16	10/43 (23.3%)	12
Weight increased	1/44 (2.3%)	1	3/43 (7%)	5
Metabolism and nutrition disorders
Decreased appetite	11/44 (25%)	14	11/43 (25.6%)	17
Hypercalcaemia	3/44 (6.8%)	3	3/43 (7%)	3
Hypokalaemia	11/44 (25%)	15	2/43 (4.7%)	5
Hypomagnesaemia	16/44 (36.4%)	29	15/43 (34.9%)	35
Hyponatraemia	3/44 (6.8%)	4	1/43 (2.3%)	1
Hypophosphataemia	2/44 (4.5%)	6	5/43 (11.6%)	12
Musculoskeletal and connective tissue disorders
Back pain	4/44 (9.1%)	4	1/43 (2.3%)	1
Neck pain	3/44 (6.8%)	6	4/43 (9.3%)	10
Pain in extremity	0/44 (0%)	0	3/43 (7%)	3
Nervous system disorders
Dizziness	4/44 (9.1%)	4	2/43 (4.7%)	2
Dysgeusia	4/44 (9.1%)	4	0/43 (0%)	0
Headache	3/44 (6.8%)	4	5/43 (11.6%)	6
Paraesthesia	3/44 (6.8%)	3	0/43 (0%)	0
Psychiatric disorders
Anxiety	2/44 (4.5%)	2	3/43 (7%)	3
Depression	2/44 (4.5%)	2	3/43 (7%)	3
Insomnia	4/44 (9.1%)	4	4/43 (9.3%)	6
Respiratory, thoracic and mediastinal disorders
Cough	5/44 (11.4%)	7	5/43 (11.6%)	5
Dyspnoea	7/44 (15.9%)	12	5/43 (11.6%)	8
Haemoptysis	4/44 (9.1%)	5	3/43 (7%)	3
Skin and subcutaneous tissue disorders
Dermatitis acneiform	15/44 (34.1%)	20	8/43 (18.6%)	17
Dry skin	6/44 (13.6%)	7	7/43 (16.3%)	8
Pruritus	3/44 (6.8%)	3	3/43 (7%)	3
Rash	20/44 (45.5%)	42	21/43 (48.8%)	28
Rash Maculo-Papular	3/44 (6.8%)	5	2/43 (4.7%)	2
Skin fissures	7/44 (15.9%)	8	6/43 (14%)	13
Skin toxicity	0/44 (0%)	0	3/43 (7%)	3
Vascular disorders
Hypertension	2/44 (4.5%)	2	3/43 (7%)	4
Hypotension	3/44 (6.8%)	3	4/43 (9.3%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.