Study of Gemcitabine and Cisplatin With or Without Cetuximab in Urothelial Cancer

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00645593
• Collaborator: National Comprehensive Cancer Network (Other), Bristol-Myers Squibb (Industry), Eli Lilly and Company (Industry)
• Enrollment: 89
• Locations: 14
• Arms: 2
• Duration (Months): 87
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will compare the effects, good and/or bad, of chemotherapy (Gemcitabine and Cisplatin) with or without the addition of the chemotherapy drug Cetuximab to find out which treatment is better.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: Gemcitabine,; Drug: Cisplatin; Drug: Cetuximab	Phase 2

Detailed Description

Urothelial cancer typically begins in the lining of the bladder, the balloon-shaped organ in the pelvic area that stores urine. Urothelial cancer can also begin in the ureter (the tube connecting the kidney and bladder), part of the kidney itself, or the urethra (the tube you pass urine out of). Some Urothelial cancers remain confined to the lining, while in other cases they spread to other areas. Treatment for these cancers varies greatly depending on the stage of disease at the time of diagnosis. Study participants in this research study will have a diagnosis of urothelial cancer that is advanced or has come back after prior therapy.

There are two standard chemotherapeutic regimens for the management of this disease. One is the combination of the drugs, methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). However the toxicities associated with this treatment regimen (side effects) is high.

The other is a combination of two drugs called Cisplatin and Gemcitabine. These drugs are also known to destroy urothelial cancer cells, and are better tolerated by patients. All study participants will receive both of these drugs.

Another anti-cancer drug called Cetuximab is known to delay or prevent tumor growth and in some cases to lead to death of cancer cells by blocking certain cellular pathways that lead to tumor development. This drug has been approved by the United States Food and Drug Administration (FDA) for the treatment of colorectal cancer and for treatment of head and neck cancers. The use of Cetuximab for the treatment of urothelial cancer is investigational in this study.

The purpose of this study is to compare the safety and efficacy of Gemcitabine and Cisplatin administered with or without the addition of Cetuximab in study participants with urothelial cancer.

This is a randomized research study. Study participants will be randomized to receive either gemcitabine and cisplatin alone or in combination with Cetuximab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Trial of Gemcitabine and Cisplatin With or Without Cetuximab in Patients With Urothelial Carcinoma
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1, Gemcitabine and Cisplatin Gemcitabine and Cisplatin, as described in the intervention	Drug: Gemcitabine,; Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.; Other Names: Gemzar ; Drug: Cisplatin; Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle.
Experimental: Arm 2, Cetuximab, Gemcitabine and Cisplatin Gemcitabine and Cisplatin with Cetuximab, as described in the intervention	Drug: Gemcitabine,; Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.; Other Names: Gemzar ; Drug: Cisplatin; Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle.; Drug: Cetuximab; Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.; Other Names: Erbitux

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants That Respond to Treatment in Arm 1 and Arm 2 [3 years]

   The primary objective is to compare the overall response rate of participants with locally advanced or metastatic urothelial carcinoma treated with gemcitabine and cisplatin with or without cetuximab. Overall response rate is defined as the percentage of participants that experience Complete Response (CR) (Disappearance of all target lesions) or Partial Response (PR) (>=30% decrease in the sum of the longest diameter of target lesions).

Secondary Outcome Measures

1. The Number of Grade 3 to 5 Adverse Events Experienced by Arm 1 and Arm 2 [3 years]

   One of the secondary outcomes was to assess the safety and tolerability of treatment for both arms. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were utilized for adverse event reporting.

2. Median Progression-free Survival Time in Months [3 years]

   Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions.

3. Median Overall Survival in Months [3 years]

   Median overall survival in months is provided. One participant who progressed from chemotherapy in arm 1 received cyclophosphamide and achieved long-term disease control therefore there is no upper limit for the 95% confidence interval.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Study participants will be male or female at least 18 years of age

• Study participants will have a histologic/cytologic diagnosis of urothelial carcinoma (transitional cell carcinoma; either pure or mixed histology) that is metastatic, locally recurrent, or unresectable (T4bN0 or any T, N2030)

• Study participants must have measurable disease by radiologic imaging. Study participants that have received previous radiation therapy, recovered from side effects and have not had more than 25% of the bone marrow

• Study participants must have adequate bone marrow function

Exclusion Criteria:

• Study participants may not have received previous systemic chemotherapy for the current stage of disease with the following exception: prior neoadjuvant or adjuvant chemotherapy is allowed provided it has been at least 6 months since treatment with non-cisplatin containing regimens and > 1 year since treatment with a cisplatin containing regimen

• Study participants may not have received prior therapy targeting the EGFR pathway

• Study participants may not have a history or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan

• Study participants may not have known HIV due to the intense nature of the chemotherapy in this trial

• Study subjects may not have a history of congestive heart failure (CHF), chronic renal failure, active TIAs, recent (in the last 6 months) stroke, symptomatic pulmonary embolism (PE), or myocardial infarction.

• Study participants with history of DVT or incidental or asymptomatic PE will be eligible for the study as deemed appropriate by the treating physician provided they continue prophylactic or full dose anticoagulation as per standards of care for the specific event.

• Study participants must not have a prior grade 3 or 4 severe infusion reaction to monoclonal antibodies

• Study participants may not be pregnant or breastfeeding

• Study participants may not receive concurrent treatment on another therapeutic clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Cancer Center	Duarte	California	United States	91010
2	Kenneth J. Norris Jr. Comprehensive Cancer Center, Keck School of Medicine, University of Southern California	Los Angeles	California	United States	90033
3	Stanford University	Stanford	California	United States	94305
4	Robert H. Lurie Comprehensive Cancer Center, Center of Northwestern University	Chicago	Illinois	United States	60611
5	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231
6	Boston Medical Center	Boston	Massachusetts	United States	02118
7	Lahey Clinic	Burlington	Massachusetts	United States	01805
8	University of Michigan	Ann Arbor	Michigan	United States	48109
9	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
10	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
11	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
12	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030-3721
13	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
14	University of Washington	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center
• National Comprehensive Cancer Network
• Bristol-Myers Squibb
• Eli Lilly and Company

Investigators

• Principal Investigator: Maha Hussain, M.D., University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00645593
• Other Study ID Numbers: UMCC 2007.097
• First Posted: Mar 27, 2008
• Last Update Posted: May 23, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by University of Michigan Rogel Cancer Center: Bladder Cancer
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Gemcitabine; Cetuximab

Study Results

Participant Flow

Arm/Group Title	Arm 1, Gemcitabine and Cisplatin	Arm 2, Cetuximab, Gemcitabine and Cisplatin
Arm/Group Description	Gemcitabine, Cisplatin: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.	Gemcitabine, Cisplatin and Cetuximab: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 800 mg/m2 on Days 1, 8 and 15 of cycle. Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.
Period Title: Overall Study
STARTED	29	60
COMPLETED	28	60
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Arm 1, Gemcitabine and Cisplatin	Arm 2, Cetuximab, Gemcitabine and Cisplatin	Total
Arm/Group Description	Gemcitabine, Cisplatin: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.	Gemcitabine, Cisplatin and Cetuximab: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 800 mg/m2 on Days 1, 8 and 15 of cycle. Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.	Total of all reporting groups
Overall Participants	28	60	88
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65.8	60.9	61
Sex: Female, Male (Count of Participants)
Female	5 17.9%	14 23.3%	19 21.6%
Male	23 82.1%	46 76.7%	69 78.4%
ECOG performance status (participants) [Number]
0	18 64.3%	33 55%	51 58%
1	8 28.6%	26 43.3%	34 38.6%
2	2 7.1%	1 1.7%	3 3.4%
Bladder primary (participants) [Number]
Number [participants]	20 71.4%	45 75%	65 73.9%
Distant metastasis (participants) [Number]
Number [participants]	26 92.9%	54 90%	80 90.9%
Local recurrence (participants) [Number]
Number [participants]	1 3.6%	2 3.3%	3 3.4%
Unresectable disease (participants) [Number]
Number [participants]	1 3.6%	4 6.7%	5 5.7%
Prior cystectomy or nephroureterectomy (participants) [Number]
Number [participants]	10 35.7%	13 21.7%	23 26.1%
Primary in place (participants) [Number]
Number [participants]	18 64.3%	47 78.3%	65 73.9%
Prior neoadjuvant or or adjuvant chemotherapy (participants) [Number]
Number [participants]	6 21.4%	8 13.3%	14 15.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants That Respond to Treatment in Arm 1 and Arm 2
Description	The primary objective is to compare the overall response rate of participants with locally advanced or metastatic urothelial carcinoma treated with gemcitabine and cisplatin with or without cetuximab. Overall response rate is defined as the percentage of participants that experience Complete Response (CR) (Disappearance of all target lesions) or Partial Response (PR) (>=30% decrease in the sum of the longest diameter of target lesions).
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

29 patients were enrolled and randomized to arm 1 and 60 patients were enrolled and randomized to arm 2. 1 patient from arm 1 was found to be ineligible and 3 patients from arm 2 withdrew consent (1 prior to treatment and 2 prior to 4 weeks of treatment). Only 28 patients from arm 1 and 57 patients from arm 2 were analyzed.

Arm/Group Title	Arm 1, Gemcitabine and Cisplatin	Arm 2, Cetuximab, Gemcitabine and Cisplatin
Arm/Group Description	Gemcitabine, Cisplatin: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.	Gemcitabine, Cisplatin and Cetuximab: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 800 mg/m2 on Days 1, 8 and 15 of cycle. Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.
Measure Participants	28	57
Number (95% Confidence Interval) [percentage of participants]	57.1 203.9%	61.4 102.3%

2. Secondary Outcome

Title	The Number of Grade 3 to 5 Adverse Events Experienced by Arm 1 and Arm 2
Description	One of the secondary outcomes was to assess the safety and tolerability of treatment for both arms. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were utilized for adverse event reporting.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Although 60 participants were enrolled and randomized to arm 2, 1 participant withdrew consent prior to treatment and was therefore excluded from toxicity analysis.

Arm/Group Title	Arm 1, Gemcitabine and Cisplatin	Arm 2, Cetuximab, Gemcitabine and Cisplatin
Arm/Group Description	Gemcitabine, Cisplatin: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.	Gemcitabine, Cisplatin and Cetuximab: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 800 mg/m2 on Days 1, 8 and 15 of cycle. Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.
Measure Participants	28	59
Number [adverse events]	75	83

3. Secondary Outcome

Title	Median Progression-free Survival Time in Months
Description	Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

29 patients were enrolled and randomized to arm 1 and 60 patients were enrolled and randomized to arm 2. 1 patient from arm 1 was found to be ineligible and 3 patients from arm 2 withdrew consent (1 prior to treatment and 2 prior to 4 weeks of treatment). Only 28 patients from arm 1 and 57 patients from arm 2 were analyzed.

Arm/Group Title	Arm 1, Gemcitabine and Cisplatin	Arm 2, Cetuximab, Gemcitabine and Cisplatin
Arm/Group Description	Gemcitabine, Cisplatin: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.	Gemcitabine, Cisplatin and Cetuximab: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 800 mg/m2 on Days 1, 8 and 15 of cycle. Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.
Measure Participants	28	57
Median (95% Confidence Interval) [months]	8.5	7.6

4. Secondary Outcome

Title	Median Overall Survival in Months
Description	Median overall survival in months is provided. One participant who progressed from chemotherapy in arm 1 received cyclophosphamide and achieved long-term disease control therefore there is no upper limit for the 95% confidence interval.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

29 patients were enrolled and randomized to arm 1 and 60 patients were enrolled and randomized to arm 2. 1 patient from arm 1 was found to be ineligible and 3 patients from arm 2 withdrew consent (1 prior to treatment and 2 prior to 4 weeks of treatment). Only 28 patients from arm 1 and 57 patients from arm 2 were analyzed.

Arm/Group Title	Arm 1, Gemcitabine and Cisplatin	Arm 2, Cetuximab, Gemcitabine and Cisplatin
Arm/Group Description	Gemcitabine, Cisplatin: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.	Gemcitabine, Cisplatin and Cetuximab: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 800 mg/m2 on Days 1, 8 and 15 of cycle. Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.
Measure Participants	28	57
Median (95% Confidence Interval) [Months]	17.4	14.3

Adverse Events

Arm/Group Title	Arm 1, Gemcitabine and Cisplatin		Arm 2, Cetuximab, Gemcitabine and Cisplatin
Arm/Group Description	Gemcitabine, Cisplatin: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.		Gemcitabine, Cisplatin and Cetuximab: Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle. Gemcitabine will be administered intravenously at a dose of 800 mg/m2 on Days 1, 8 and 15 of cycle. Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.
All Cause Mortality
	Arm 1, Gemcitabine and Cisplatin		Arm 2, Cetuximab, Gemcitabine and Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1, Gemcitabine and Cisplatin		Arm 2, Cetuximab, Gemcitabine and Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/29 (55.2%)		36/60 (60%)
Blood and lymphatic system disorders
Anemia	0/29 (0%)	0	2/60 (3.3%)	2
Cardiac disorders
Hypertension	1/29 (3.4%)	1	0/60 (0%)	0
Supraventricular and nodal arrhythmia	1/29 (3.4%)	1	0/60 (0%)	0
Cardiac General - Other	0/29 (0%)	0	1/60 (1.7%)	1
Gastrointestinal disorders
Hemorrhage, GI	1/29 (3.4%)	1	1/60 (1.7%)	1
Nausea	1/29 (3.4%)	1	5/60 (8.3%)	7
Vomiting	1/29 (3.4%)	1	2/60 (3.3%)	2
Colitis, infectious (e.g., Clostridium difficile)	0/29 (0%)	0	1/60 (1.7%)	1
Dysphagia (difficulty swallowing)	0/29 (0%)	0	1/60 (1.7%)	1
Obstruction, GI	0/29 (0%)	0	1/60 (1.7%)	1
Typhlitis (cecal inflammation)	0/29 (0%)	0	1/60 (1.7%)	1
Ulcer, GI	0/29 (0%)	0	1/60 (1.7%)	1
General disorders
Febrile neutropenia (fever of unknown origin without documented infection)	2/29 (6.9%)	2	2/60 (3.3%)	2
Pain	2/29 (6.9%)	2	5/60 (8.3%)	5
Death not associated with CTCAE term	0/29 (0%)	0	2/60 (3.3%)	2
Edema: limb	0/29 (0%)	0	1/60 (1.7%)	1
Fatigue (asthenia, lethargy, malaise)	0/29 (0%)	0	3/60 (5%)	4
Fever (in the absence of neutropenia)	0/29 (0%)	0	1/60 (1.7%)	1
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	0/29 (0%)	0	1/60 (1.7%)	1
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	2/29 (6.9%)	2	1/60 (1.7%)	1
Infection - Other	1/29 (3.4%)	1	1/60 (1.7%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils	3/29 (10.3%)	3	7/60 (11.7%)	7
Infection with unknown ANC	0/29 (0%)	0	3/60 (5%)	3
Investigations
Leukocytes (total WBC)	1/29 (3.4%)	1	3/60 (5%)	3
Neutrophils/granulocytes (ANC/AGC)	5/29 (17.2%)	5	8/60 (13.3%)	10
Platelets	1/29 (3.4%)	3	7/60 (11.7%)	11
ALT, SGPT (serum glutamic pyruvic transaminase)	0/29 (0%)	0	1/60 (1.7%)	1
AST, SGOT(serum glutamic oxaloacetic transaminase)	0/29 (0%)	0	1/60 (1.7%)	1
Metabolism and nutrition disorders
Dehydration	1/29 (3.4%)	1	0/60 (0%)	0
Anorexia	0/29 (0%)	0	1/60 (1.7%)	1
Magnesium, serum-low (hypomagnesemia)	0/29 (0%)	0	3/60 (5%)	5
Sodium, serum-low (hyponatremia)	0/29 (0%)	0	2/60 (3.3%)	2
Musculoskeletal and connective tissue disorders
Fracture	0/29 (0%)	0	1/60 (1.7%)	1
Muscle weakness, generalized or specific area (not due to neuropathy)	0/29 (0%)	0	1/60 (1.7%)	1
Nervous system disorders
Confusion	1/29 (3.4%)	1	0/60 (0%)	0
Neurology - Other	1/29 (3.4%)	1	0/60 (0%)	0
Ataxia (incoordination)	0/29 (0%)	0	2/60 (3.3%)	2
Cognitive disturbance	0/29 (0%)	0	1/60 (1.7%)	1
Confusion	0/29 (0%)	0	1/60 (1.7%)	3
Dizziness	0/29 (0%)	0	1/60 (1.7%)	1
Insomnia	0/29 (0%)	0	1/60 (1.7%)	1
Memory impairment	0/29 (0%)	0	1/60 (1.7%)	1
Neuropathy: motor	0/29 (0%)	0	2/60 (3.3%)	2
Neuropathy: sensory	0/29 (0%)	0	1/60 (1.7%)	1
Syncope (fainting)	0/29 (0%)	0	1/60 (1.7%)	1
Renal and urinary disorders
Renal failure	1/29 (3.4%)	1	1/60 (1.7%)	1
Hemorrhage, GU	0/29 (0%)	0	1/60 (1.7%)	1
Obstruction, GU	0/29 (0%)	0	1/60 (1.7%)	1
Urinary retention (including neurogenic bladder)	0/29 (0%)	0	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates	1/29 (3.4%)	1	0/60 (0%)	0
Pulmonary/Upper Respiratory - Other (Specify)	0/29 (0%)	0	1/60 (1.7%)	1
Skin and subcutaneous tissue disorders
Rash: acne/acneiform	0/29 (0%)	0	1/60 (1.7%)	1
Ulceration	0/29 (0%)	0	1/60 (1.7%)	1
Vascular disorders
CNS cerebrovascular ischemia	1/29 (3.4%)	1	2/60 (3.3%)	2
Thrombosis/thrombus/embolism	3/29 (10.3%)	3	7/60 (11.7%)	8
Peripheral arterial ischemia	0/29 (0%)	0	1/60 (1.7%)	1
Thrombosis/embolism (vascular access-related)	0/29 (0%)	0	6/60 (10%)	7
Other (Not Including Serious) Adverse Events
	Arm 1, Gemcitabine and Cisplatin		Arm 2, Cetuximab, Gemcitabine and Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/29 (100%)		60/60 (100%)
Blood and lymphatic system disorders
Anemia	22/29 (75.9%)	54	37/60 (61.7%)	139
Cardiac disorders
Hypertension	0/29 (0%)	0	6/60 (10%)	9
Supraventricular and nodal arrhythmia	0/29 (0%)	0	9/60 (15%)	11
Ear and labyrinth disorders
Tinnitus	5/29 (17.2%)	6	0/60 (0%)	0
Gastrointestinal disorders
Constipation	14/29 (48.3%)	23	22/60 (36.7%)	35
Diarrhea	9/29 (31%)	15	20/60 (33.3%)	42
Nausea	17/29 (58.6%)	43	38/60 (63.3%)	71
Taste alteration (dysgeusia)	9/29 (31%)	11	14/60 (23.3%)	19
Vomiting	8/29 (27.6%)	14	20/60 (33.3%)	29
Heartburn/dyspepsia	0/29 (0%)	0	15/60 (25%)	22
Mucositis/stomatitis (clinical exam)	0/29 (0%)	0	9/60 (15%)	11
Mucositis/stomatitis (functional/symptomatic)	0/29 (0%)	0	7/60 (11.7%)	7
General disorders
Fatigue (asthenia, lethargy, malaise)	23/29 (79.3%)	67	51/60 (85%)	146
Pain	29/29 (100%)	46	60/60 (100%)	136
Pain - Other	6/29 (20.7%)	7	8/60 (13.3%)	12
Edema: limb	0/29 (0%)	0	16/60 (26.7%)	22
Fever (in the absence of neutropenia)	0/29 (0%)	0	12/60 (20%)	18
Rigors/chills	0/29 (0%)	0	9/60 (15%)	12
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	0/29 (0%)	0	5/60 (8.3%)	5
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	0/29 (0%)	0	6/60 (10%)	9
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils	11/29 (37.9%)	13	28/60 (46.7%)	31
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	0/29 (0%)	0	8/60 (13.3%)	8
Infection - Other	0/29 (0%)	0	6/60 (10%)	8
Infection with unknown ANC	0/29 (0%)	0	10/60 (16.7%)	11
Investigations
Albumin, serum-low (hypoalbuminemia)	8/29 (27.6%)	12	13/60 (21.7%)	41
Creatinine	10/29 (34.5%)	39	16/60 (26.7%)	40
Leukocytes (total WBC)	12/29 (41.4%)	30	31/60 (51.7%)	114
Lymphopenia	6/29 (20.7%)	17	19/60 (31.7%)	100
Neutrophils/granulocytes (ANC/AGC)	18/29 (62.1%)	44	36/60 (60%)	100
Platelets	26/29 (89.7%)	96	45/60 (75%)	162
ALT, SGPT (serum glutamic pyruvic transaminase)	0/29 (0%)	0	12/60 (20%)	36
AST, SGOT(serum glutamic oxaloacetic transaminase)	0/29 (0%)	0	11/60 (18.3%)	38
Alkaline phosphatase	0/29 (0%)	0	8/60 (13.3%)	22
Weight loss	0/29 (0%)	0	11/60 (18.3%)	14
Metabolism and nutrition disorders
Anorexia	15/29 (51.7%)	18	27/60 (45%)	44
Dehydration	8/29 (27.6%)	10	15/60 (25%)	19
Glucose, serum-high (hyperglycemia)	13/29 (44.8%)	43	20/60 (33.3%)	96
Magnesium, serum-low (hypomagnesemia)	6/29 (20.7%)	18	31/60 (51.7%)	132
Potassium, serum-high (hyperkalemia)	7/29 (24.1%)	15	11/60 (18.3%)	32
Sodium, serum-low (hyponatremia)	7/29 (24.1%)	23	7/60 (11.7%)	11
Calcium, serum-low (hypocalcemia)	0/29 (0%)	0	11/60 (18.3%)	18
Dehydration	0/29 (0%)	0	15/60 (25%)	19
Magnesium, serum-high (hypermagnesemia)	0/29 (0%)	0	6/60 (10%)	18
Sodium, serum-high (hypernatremia)	0/29 (0%)	0	5/60 (8.3%)	9
Sodium, serum-low (hyponatremia)	0/29 (0%)	0	21/60 (35%)	49
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)	0/29 (0%)	0	7/60 (11.7%)	9
Nervous system disorders
Dizziness	5/29 (17.2%)	6	16/60 (26.7%)	32
Mood alteration	7/29 (24.1%)	9	13/60 (21.7%)	20
Neuropathy: sensory	8/29 (27.6%)	10	16/60 (26.7%)	22
Insomnia	0/29 (0%)	0	6/60 (10%)	6
Renal and urinary disorders
Urinary frequency/urgency	5/29 (17.2%)	8	0/60 (0%)	0
Hemorrhage, GU	0/29 (0%)	0	8/60 (13.3%)	8
Respiratory, thoracic and mediastinal disorders
Cough	7/29 (24.1%)	7	12/60 (20%)	19
Dyspnea (shortness of breath)	6/29 (20.7%)	10	12/60 (20%)	16
Hemorrhage, pulmonary/upper respiratory	0/29 (0%)	0	5/60 (8.3%)	7
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	0/29 (0%)	0	5/60 (8.3%)	6
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)	5/29 (17.2%)	5	13/60 (21.7%)	13
Dermatology/Skin - Other (Specify)	0/29 (0%)	0	10/60 (16.7%)	20
Dry skin	0/29 (0%)	0	16/60 (26.7%)	22
Nail changes	0/29 (0%)	0	6/60 (10%)	9
Pruritus/itching	0/29 (0%)	0	11/60 (18.3%)	23
Rash/desquamation	0/29 (0%)	0	27/60 (45%)	85
Rash: acne/acneiform	0/29 (0%)	0	33/60 (55%)	118
Vascular disorders
Thrombosis/embolism (vascular access-related)	0/29 (0%)	0	8/60 (13.3%)	9
Thrombosis/thrombus/embolism	0/29 (0%)	0	9/60 (15%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.