BALI-1: Cetuximab and Cisplatin in the Treatment of "Triple Negative" (Estrogen Receptor [ER] Negative, Progesterone Receptor [PgR] Negative, and Human Epidermal Growth Factor Receptor 2 [HER2] Negative) Metastatic Breast Cancer

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00463788
• Collaborator: (none)
• Enrollment: 181
• Locations: 46
• Arms: 2
• Duration (Months): 44.1
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine whether overall response to cetuximab combined with cisplatin is better than overall response to cisplatin alone together with showing that the overall response for cetuximab and cisplatin was above a pre-specified threshold of 0.2 in the treatment of "triple negative" metastatic breast cancer.

The secondary objective of this study is to compare the differences between the two treatment groups using the following criteria : Progression-Free Survival (PFS) Time, Overall Survival (OS), Time to Response (TTR) and Safety.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasm	Drug: cetuximab, cisplatin; Drug: cisplatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 181 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Trial With Cetuximab and Cisplatin in the Treatment of ER-negative, PgR-negative, HER2-negative Metastatic Breast Carcinoma ("Basal Like")
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cisplatin and cetuximab	Drug: cetuximab, cisplatin; Subjects will receive an initial dose of cetuximab 400 milligram per square meter (mg/m^2) followed by weekly doses of 250 mg/m^2. All doses will be given by intravenous (IV) infusion. Subjects will receive cisplatin (75 mg/m^2 IV on Day 1) every 3 weeks, with a maximum of 6 cycles. Administration of the Investigational Medicinal Product (IMP) will be stopped upon the first occurrence of disease progression, unacceptable toxicity or withdrawal of consent.
Active Comparator: cisplatin	Drug: cisplatin; Subjects will receive cisplatin (75 mg/m^2 IV on Day 1) every 3 weeks, with a maximum of 6 cycles. Subjects have the option of receiving cetuximab plus cisplatin at progression within the first 6 cycles, or cetuximab alone at progression after the 6 cycles. Administration of the IMP will be stopped upon the first occurrence of disease progression (except in cisplatin arm where switch to cetuximab plus cisplatin, or cetuximab alone is possible), unacceptable toxicity or withdrawal of consent.

Outcome Measures

Primary Outcome Measures

1. Best Overall Response (BOR) [Evaluations were performed every 6 weeks until progression reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009]

   Percentage of participants with best overall (objective) response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).

Secondary Outcome Measures

1. Progression-Free Survival (PFS) Time [Time from randomization to disease progression, death or last tumour assessment, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009]

   The PFS was defined as the duration from randomization until radiological progression according to investigator (based on RECIST) or death due to any cause. Only deaths within 85 days of last tumor assessment were considered. Participants without event were censored on the date of last tumor assessment.

2. Overall Survival (OS) Time [Time from randomization to death or last day known to be alive, reported between day of first participant randomized, 20 June 2007, until cut-off date, 05 April 2010]

   The OS time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date, whatever was earlier.

3. Time to Response (TTR) [Time from the first dose of study treatment (cetuximab or cisplatin) to first assessment of CR or PR, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009]

   The TTR was determined for participants whose confirmed BOR (based on RECIST) was either a CR or a PR . It was defined as the time from the first dose study treatment until the date of the first assessment of confirmed CR or PR.

4. Safety- Number of Participants Experiencing Any Adverse Event (AE) [Time from first dose up to 30 days after last dose of study treatment, reported between day of first dose of study treatment, 20 June 2007, until cut-off date 05 April 2010]

   Number of participants experiencing any AE. AEs: Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed diagnosis of metastatic breast cancer (Stage IV)

• Estrogen Receptor [ER] negative, PgR negative and HER2 less than 3+ expression by immunohistochemistry (IHC)

• No more than 1 prior chemotherapy received for treating this metastatic breast cancer

• No more than 1 prior anthracycline and/or taxane regimen (either adjuvant or metastatic setting)

• Other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Prior platinum agent

• Prior mitomycin

• Known history of brain metastases

• Other protocol-defined exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Campbelltown	New South Wales	Australia
2	Research Site	Liverpool	New South Wales	Australia
3	Research Site	Wollongong	New South Wales	Australia
4	Research Site	Malvern	Victoria	Australia
5	Research Site	Perth	Western Australia	Australia
6	Research Site	Bludesch-Gais		Austria
7	Research Site	Salzburg		Austria
8	Research Site	Wien		Austria
9	Research Site	Brussels		Belgium
10	Research Site	Edegem		Belgium
11	Research Site	Gent		Belgium
12	Research Site	Liège		Belgium
13	Research Site	Namur		Belgium
14	Research Site	Wilrijk		Belgium
15	Research Site	Frankfurt am Main		Germany
16	Research Site	Heidelberg		Germany
17	Research Site	Kiel		Germany
18	Research Site	Köln		Germany
19	Research Site	München		Germany
20	Research Site	Rostock		Germany
21	Research Site	Dublin		Ireland
22	Research Site	Beer Sheba		Israel
23	Research Site	Haifa		Israel
24	Research Site	Jerusalem		Israel
25	Research Site	Kefar Sava		Israel
26	Research Site	Petah Tikva		Israel
27	Research Site	Rehovot		Israel
28	Research Site	Tel Aviv		Israel
29	Research Site	Tel Hashomer		Israel
30	Research Site	Genova		Italy
31	Research Site	Modena		Italy
32	Research Site	Christchurch		New Zealand
33	Research Site	Wellington		New Zealand
34	Research Site	Coimbra		Portugal
35	Research Site	Lisboa		Portugal
36	Research Site	Porto		Portugal
37	Research Site	Barcelona		Spain
38	Research Site	Madrid		Spain
39	Research Site	Murcia		Spain
40	Research Site	Palma de Mallorca		Spain
41	Research Site	Valencia		Spain
42	Research Site	Zaragoza		Spain
43	Research Site	Cardiff		United Kingdom
44	Research Site	Guildford		United Kingdom
45	Research Site	London		United Kingdom
46	Research Site	Manchester		United Kingdom

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany

Investigators

• Principal Investigator: José Baselga, Prof., General Hospital, Boston, Massachusetts, USA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT00463788
• Other Study ID Numbers: EMR 200027-051
• First Posted: Apr 20, 2007
• Last Update Posted: Feb 13, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Merck KGaA, Darmstadt, Germany: cancer; breast; metastatic; triple negative
• Additional relevant MeSH terms: Breast Neoplasms; Cisplatin; Cetuximab

Study Results

Participant Flow

Pre-assignment Detail	Following a mandate of the Spanish health authority, data from all participants at site 0904 (Spain) were excluded from analyses due to evidence of misconduct, with significant deviations from Good Clinical Practice guidelines. Therefore, 173 of the 181 randomized participants were considered in the full analysis set (FAS).

Arm/Group Title	Cisplatin and Cetuximab	Cisplatin
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly. Participants who demonstrated at least stable disease (SD) up to 6 cycles of cisplatin continued treatment with cetuximab only until progressive disease (PD) or occurrence of unacceptable toxicity.	Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of PD, unacceptable toxicity or withdrawal of consent.
Period Title: Overall Study
STARTED	115	58
Treated	114	57
COMPLETED	6	4
NOT COMPLETED	109	54

Baseline Characteristics

Arm/Group Title	Cisplatin and Cetuximab	Cisplatin	Total
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly. Participants who demonstrated at least stable disease (SD) up to 6 cycles of cisplatin continued treatment with cetuximab only until progressive disease (PD) or occurrence of unacceptable toxicity.	Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of PD, unacceptable toxicity or withdrawal of consent.	Total of all reporting groups
Overall Participants	115	58	173
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.9 (12.53)	51.7 (10.67)	52.5 (11.92)
Age, Customized (participants) [Number]
< 65 years	93 80.9%	51 87.9%	144 83.2%
>= 65 years	22 19.1%	7 12.1%	29 16.8%
Sex: Female, Male (Count of Participants)
Female	115 100%	58 100%	173 100%
Male	0 0%	0 0%	0 0%
Naturally post menopausal participants (participants) [Number]
Yes	64 55.7%	36 62.1%	100 57.8%
No	51 44.3%	22 37.9%	73 42.2%
Duration of breast cancer from primary tumor diagnosis to informed consent (months) [Median (Full Range) ]
Median (Full Range) [months]	19.2	17.3	18.7
Participants categorized by site of metastasis (participants) [Number]
Lung	64 55.7%	26 44.8%	90 52%
Lymph nodes (by medical review)	49 42.6%	22 37.9%	71 41%
Bone	37 32.2%	20 34.5%	57 32.9%
Liver	36 31.3%	17 29.3%	53 30.6%
Skin	20 17.4%	8 13.8%	28 16.2%
Other	15 13%	8 13.8%	23 13.3%
Duration of metastatic breast cancer from metastasis to informed consent (months) [Median (Full Range) ]
Median (Full Range) [months]	0.9	0.8	0.9
Duration from initial breast cancer diagnosis to date of metastasis (months) [Median (Full Range) ]
Median (Full Range) [months]	15.7	15.4	15.5

Outcome Measures

1. Primary Outcome

Title	Best Overall Response (BOR)
Description	Percentage of participants with best overall (objective) response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame	Evaluations were performed every 6 weeks until progression reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009

Outcome Measure Data

Analysis Population Description

FAS population included all participants who were randomized as described in the pre-assignment details.

Arm/Group Title	Cisplatin and Cetuximab	Cisplatin
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly. Participants who demonstrated at least stable disease (SD) up to 6 cycles of cisplatin continued treatment with cetuximab only until progressive disease (PD) or occurrence of unacceptable toxicity.	Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of PD, unacceptable toxicity or withdrawal of consent.
Measure Participants	115	58
Number (95% Confidence Interval) [percentage of participants]	20.0 17.4%	10.3 17.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cisplatin and Cetuximab, Cisplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1109
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Randomization strata: first- or second line according to Interactive Voice Response System (IVRS).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.126
	Confidence Interval	(2-Sided) 95%; 0.809 to 5.591
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-Free Survival (PFS) Time
Description	The PFS was defined as the duration from randomization until radiological progression according to investigator (based on RECIST) or death due to any cause. Only deaths within 85 days of last tumor assessment were considered. Participants without event were censored on the date of last tumor assessment.
Time Frame	Time from randomization to disease progression, death or last tumour assessment, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009

Outcome Measure Data

Analysis Population Description

FAS population included all participants who were randomized as described in the pre-assignment details.

Arm/Group Title	Cisplatin and Cetuximab	Cisplatin
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly. Participants who demonstrated at least stable disease (SD) up to 6 cycles of cisplatin continued treatment with cetuximab only until progressive disease (PD) or occurrence of unacceptable toxicity.	Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of PD, unacceptable toxicity or withdrawal of consent.
Measure Participants	115	58
Median (95% Confidence Interval) [months]	3.7	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cisplatin and Cetuximab, Cisplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0324
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.675
	Confidence Interval	(2-Sided) 95%; 0.470 to 0.969
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Survival (OS) Time
Description	The OS time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date, whatever was earlier.
Time Frame	Time from randomization to death or last day known to be alive, reported between day of first participant randomized, 20 June 2007, until cut-off date, 05 April 2010

Outcome Measure Data

Analysis Population Description

FAS population included all participants who were randomized as described in the pre-assignment details.

Arm/Group Title	Cisplatin and Cetuximab	Cisplatin
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly. Participants who demonstrated at least stable disease (SD) up to 6 cycles of cisplatin continued treatment with cetuximab only until progressive disease (PD) or occurrence of unacceptable toxicity.	Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of PD, unacceptable toxicity or withdrawal of consent.
Measure Participants	115	58
Median (95% Confidence Interval) [months]	12.9	9.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cisplatin and Cetuximab, Cisplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3121
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.821
	Confidence Interval	(2-Sided) 95%; 0.561 to 1.204
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Response (TTR)
Description	The TTR was determined for participants whose confirmed BOR (based on RECIST) was either a CR or a PR . It was defined as the time from the first dose study treatment until the date of the first assessment of confirmed CR or PR.
Time Frame	Time from the first dose of study treatment (cetuximab or cisplatin) to first assessment of CR or PR, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009

Outcome Measure Data

Analysis Population Description

FAS population included all participants who were randomized as described in the pre-assignment details.

Arm/Group Title	Cisplatin and Cetuximab	Cisplatin
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly. Participants who demonstrated at least stable disease (SD) up to 6 cycles of cisplatin continued treatment with cetuximab only until progressive disease (PD) or occurrence of unacceptable toxicity.	Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of PD, unacceptable toxicity or withdrawal of consent.
Measure Participants	115	58
Median (95% Confidence Interval) [months]	1.4	1.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cisplatin and Cetuximab, Cisplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5993
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.754
	Confidence Interval	(2-Sided) 95%; 0.262 to 2.170
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Safety- Number of Participants Experiencing Any Adverse Event (AE)
Description	Number of participants experiencing any AE. AEs: Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications.
Time Frame	Time from first dose up to 30 days after last dose of study treatment, reported between day of first dose of study treatment, 20 June 2007, until cut-off date 05 April 2010

Outcome Measure Data

Analysis Population Description

Safety population included all the participants who received at least 1 dose of study medication (that is cisplatin or cetuximab).

Arm/Group Title	Cisplatin and Cetuximab	Cisplatin
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly. Participants who demonstrated at least stable disease (SD) up to 6 cycles of cisplatin continued treatment with cetuximab only until progressive disease (PD) or occurrence of unacceptable toxicity.	Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of PD, unacceptable toxicity or withdrawal of consent.
Measure Participants	114	57
Number [participants]	114 99.1%	57 98.3%

Adverse Events

Time Frame	Time from first dose up to 30 days after last dose of study treatment, reported between day of first dose of study treatment, 20 June 2007, until cut-off date 05 April 2010
Adverse Event Reporting Description	An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship.
Arm/Group Title	Cisplatin and Cetuximab		Cisplatin		Cisplatin Alone Switched to Cetuximab
Arm/Group Description	Cisplatin 75 milligram per square meter (mg/m^2) intravenous (IV) infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles and cetuximab initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion weekly.		Cisplatin 75 mg/m^2 IV infusion administered on Day 1 until every 3 weeks with a maximum of 6 cycles until the first occurrence of progressive disease (PD), unacceptable toxicity or withdrawal of consent.		On progression, participants in the cisplatin group had the option to switch to cisplatin (75 mg/m^2 IV infusion) plus cetuximab (initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion) if the progressive disease was reported during the 6 cisplatin cycles or to cetuximab alone (initially 400 mg/m^2 followed by 250 mg/m^2 IV infusion) if the progression was reported after the 6 cisplatin cycles.
All Cause Mortality
	Cisplatin and Cetuximab		Cisplatin		Cisplatin Alone Switched to Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cisplatin and Cetuximab		Cisplatin		Cisplatin Alone Switched to Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/114 (36%)		13/57 (22.8%)		6/31 (19.4%)
Blood and lymphatic system disorders
Anaemia	3/114 (2.6%)		0/57 (0%)		0/31 (0%)
Leukopenia	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Thrombocytopenia	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Cardiac disorders
Tachycardia	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Gastrointestinal disorders
Abdominal Distention	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Abdomial Pain	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Diarrhoea	3/114 (2.6%)		0/57 (0%)		0/31 (0%)
Intestinal Obstruction	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Melaena	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Nausea	2/114 (1.8%)		0/57 (0%)		0/31 (0%)
Vomiting	1/114 (0.9%)		1/57 (1.8%)		0/31 (0%)
General disorders
Asthenia	2/114 (1.8%)		0/57 (0%)		0/31 (0%)
Fatigue	3/114 (2.6%)		0/57 (0%)		0/31 (0%)
General Physical Health Deterioration	4/114 (3.5%)		1/57 (1.8%)		2/31 (6.5%)
Pyrexia	4/114 (3.5%)		2/57 (3.5%)		1/31 (3.2%)
Hepatobiliary disorders
Hepatic Function Abnormal	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Immune system disorders
Drug Hypersensitivity	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Infections and infestations
Catheter Site Infection	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Cellulitis	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Device Related Infection	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Erysipelas	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Infection	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Pneumonia	2/114 (1.8%)		1/57 (1.8%)		0/31 (0%)
Post Procedural Infection	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Septic Shock	1/114 (0.9%)		0/57 (0%)		1/31 (3.2%)
Sinusitis	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Skin Infection	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Soft Tissue Infection	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Streptococcal Infection	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Urinary Tract Infection	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Injury, poisoning and procedural complications
Femur Fracture	0/114 (0%)		0/57 (0%)		1/31 (3.2%)
Investigations
Oxygen Saturation Decreased	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Metabolism and nutrition disorders
Decreased Appetite	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Hypocalcaemia	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Hypomagnesaemia	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Hyponatraemia	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Osteolysis	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Pathological Fracture	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Central Nervous System	1/114 (0.9%)		1/57 (1.8%)		0/31 (0%)
Cancer Pain	0/114 (0%)		0/57 (0%)		1/31 (3.2%)
Nervous system disorders
Cerebral Haemorrhage	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Cerebrovascular Accident	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Coma Hepatic	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Dizziness	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Headache	2/114 (1.8%)		0/57 (0%)		0/31 (0%)
Renal and urinary disorders
Renal Failure	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Reproductive system and breast disorders
Pelvic Pain	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/114 (1.8%)		0/57 (0%)		0/31 (0%)
Dysphonia	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Dyspnoae	6/114 (5.3%)		1/57 (1.8%)		0/31 (0%)
Pleural Effusion	2/114 (1.8%)		1/57 (1.8%)		0/31 (0%)
Pneumothorax	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Pulmonary Embolism	4/114 (3.5%)		0/57 (0%)		2/31 (6.5%)
Respiratory Failure	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Vascular disorders
Arterial Thrombosis Limb	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Deep Vein Thrombosis	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Hypertension	1/114 (0.9%)		0/57 (0%)		0/31 (0%)
Thrombosis	0/114 (0%)		1/57 (1.8%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Cisplatin and Cetuximab		Cisplatin		Cisplatin Alone Switched to Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/114 (98.2%)		55/57 (96.5%)		28/31 (90.3%)
Blood and lymphatic system disorders
Neutropenia	33/114 (28.9%)		10/57 (17.5%)		3/31 (9.7%)
Anaemia	13/114 (11.4%)		12/57 (21.1%)		4/31 (12.9%)
Thrombocytopenia	7/114 (6.1%)		2/57 (3.5%)		0/31 (0%)
Leukopenia	7/114 (6.1%)		1/57 (1.8%)		0/31 (0%)
Ear and labyrinth disorders
Tinnitus	8/114 (7%)		10/57 (17.5%)		0/31 (0%)
Ototoxicity	3/114 (2.6%)		3/57 (5.3%)		0/31 (0%)
Vertigo	1/114 (0.9%)		3/57 (5.3%)		0/31 (0%)
Eye disorders
Conjunctivitis	9/114 (7.9%)		0/57 (0%)		0/31 (0%)
Gastrointestinal disorders
Nausea	73/114 (64%)		37/57 (64.9%)		8/31 (25.8%)
Vomiting	43/114 (37.7%)		37/57 (64.9%)		7/31 (22.6%)
Constipation	27/114 (23.7%)		16/57 (28.1%)		5/31 (16.1%)
Diarrhoea	22/114 (19.3%)		6/57 (10.5%)		3/31 (9.7%)
Stomatitis	16/114 (14%)		2/57 (3.5%)		2/31 (6.5%)
Dyspepsia	13/114 (11.4%)		5/57 (8.8%)		0/31 (0%)
Abdominal Pain	10/114 (8.8%)		1/57 (1.8%)		2/31 (6.5%)
Abdominal Pain Upper	9/114 (7.9%)		6/57 (10.5%)		0/31 (0%)
General disorders
Fatigue	56/114 (49.1%)		20/57 (35.1%)		6/31 (19.4%)
Asthenia	26/114 (22.8%)		14/57 (24.6%)		3/31 (9.7%)
Pyrexia	11/114 (9.6%)		7/57 (12.3%)		0/31 (0%)
Oedema Peripheral	10/114 (8.8%)		3/57 (5.3%)		0/31 (0%)
Pain	9/114 (7.9%)		1/57 (1.8%)		2/31 (6.5%)
General Physical Health Deterioration	4/114 (3.5%)		4/57 (7%)		0/31 (0%)
Mucosal Inflammation	0/114 (0%)		0/57 (0%)		2/31 (6.5%)
Immune system disorders
Drug Hypersensitivity	6/114 (5.3%)		0/57 (0%)		0/31 (0%)
Infections and infestations
Nasopharyngitis	7/114 (6.1%)		2/57 (3.5%)		0/31 (0%)
Nail Infection	6/114 (5.3%)		0/57 (0%)		0/31 (0%)
Folliculitis	0/114 (0%)		0/57 (0%)		2/31 (6.5%)
Investigations
Haemoglobin Decreased	2/114 (1.8%)		3/57 (5.3%)		0/31 (0%)
Weight Decreased	0/114 (0%)		0/57 (0%)		2/31 (6.5%)
Metabolism and nutrition disorders
Decreased Appetite	40/114 (35.1%)		8/57 (14%)		4/31 (12.9%)
Hypomagnesaemia	23/114 (20.2%)		4/57 (7%)		3/31 (9.7%)
Hypokalaemia	15/114 (13.2%)		1/57 (1.8%)		3/31 (9.7%)
Hypocalcaemia	6/114 (5.3%)		0/57 (0%)		2/31 (6.5%)
Musculoskeletal and connective tissue disorders
Pain in Extremity	13/114 (11.4%)		3/57 (5.3%)		2/31 (6.5%)
Back Pain	8/114 (7%)		6/57 (10.5%)		3/31 (9.7%)
Bone Pain	8/114 (7%)		3/57 (5.3%)		0/31 (0%)
Musculoskeletal Pain	2/114 (1.8%)		4/57 (7%)		0/31 (0%)
Nervous system disorders
Dysgeusia	19/114 (16.7%)		4/57 (7%)		0/31 (0%)
Peripheral Sensory Neuropathy	13/114 (11.4%)		2/57 (3.5%)		0/31 (0%)
Neuropathy Peripheral	12/114 (10.5%)		4/57 (7%)		0/31 (0%)
Headache	11/114 (9.6%)		7/57 (12.3%)		2/31 (6.5%)
Paraesthesia	4/114 (3.5%)		3/57 (5.3%)		0/31 (0%)
Psychiatric disorders
Depression	7/114 (6.1%)		2/57 (3.5%)		0/31 (0%)
Insomnia	5/114 (4.4%)		4/57 (7%)		2/31 (6.5%)
Anxiety	5/114 (4.4%)		3/57 (5.3%)		0/31 (0%)
Reproductive system and breast disorders
Breast Pain	6/114 (5.3%)		0/57 (0%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	23/114 (20.2%)		8/57 (14%)		3/31 (9.7%)
Cough	16/114 (14%)		7/57 (12.3%)		4/31 (12.9%)
Skin and subcutaneous tissue disorders
Rash	56/114 (49.1%)		1/57 (1.8%)		5/31 (16.1%)
Dry Skin	29/114 (25.4%)		1/57 (1.8%)		2/31 (6.5%)
Dermatitis Acneiform	23/114 (20.2%)		0/57 (0%)		9/31 (29%)
Alopecia	15/114 (13.2%)		3/57 (5.3%)		2/31 (6.5%)
Acne	15/114 (13.2%)		0/57 (0%)		4/31 (12.9%)
Pruritus	10/114 (8.8%)		2/57 (3.5%)		3/31 (9.7%)
Nail Disorder	6/114 (5.3%)		0/57 (0%)		2/31 (6.5%)
Vascular disorders
Hypertension	10/114 (8.8%)		2/57 (3.5%)		2/31 (6.5%)

Limitations/Caveats

Participants were randomized to 2 groups in a 2:1 ratio.

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.