Cediranib, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

• Sponsor: NCIC Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00795340
• Collaborator: (none)
• Enrollment: 306
• Locations: 19
• Arms: 2
• Actual Duration (Months): 62.3
• Patients Per Site: 16.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether cediranib is more effective than a placebo when given together with paclitaxel and carboplatin in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying how well cediranib works when given together with paclitaxel and carboplatin in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin; Drug: cediranib maleate; Drug: paclitaxel; Other: placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

• To compare overall survival of patients with stage IIIB-IV non-small cell lung cancer treated with cediranib vs placebo administered in combination with paclitaxel and carboplatin.

Secondary

• To compare the progression-free survival of patients treated with these regimens.

• To compare the objective response rates in patients treated with these regimens.

• To estimate time to response and response duration in patients treated with these regimens.

• To evaluate the nature, severity, and frequency of toxicities, including hemorrhage and hemoptysis, in patients treated with these regimens.

• To compare the pharmacokinetics of paclitaxel between the two arms in a subset of enrolled patients

• To compare the quality of life of patients treated with these regimens.

• To determine the incremental cost effectiveness and cost utility ratios for these regimens.

• To correlate the expression of tissue markers (at diagnosis) with outcomes and response in an exploratory fashion OUTLINE: This is a multicenter study. Patients are stratified by gender, center, disease stage (IIIB vs IV), weight loss (< 5% vs 5-10% vs unknown), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.

• Arm II: Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I.

Treatment in both arms repeats every 21 days for 4 to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 1 of each course, and periodically thereafter.

After completion of study therapy, patients are followed every 12 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 306 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blind Randomized Trial of Cediranib Versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer
• Actual Study Start Date: Nov 6, 2008
• Actual Primary Completion Date: Jan 9, 2012
• Actual Study Completion Date: Jan 16, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Cediranib Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.	Drug: carboplatin; Given IV; Drug: cediranib maleate; Given orally; Drug: paclitaxel; Given IV
Placebo Comparator: Arm II Placebo Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I.	Drug: carboplatin; Given IV; Drug: paclitaxel; Given IV; Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Overall Survival [at every 3 months visit throughout trial, a median of 13.1 months.]

   Medians of survival time, and their confidence intervals.

Secondary Outcome Measures

1. Progression-free Survival [at every 3 months visit throughout trial, a median of 12 months]

   Medians of PFS and their confidence intervals by arm

2. Objective Tumor Response as Assessed by RECIST Criteria v1.1. [Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.]

   Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically or cytologically* confirmed non-small cell carcinoma of the lung

• Stage IIIB or IV disease NOTE: *Diagnosis by sputum cytology alone allowed provided it is confirmed by a second sputum specimen

• Measurable disease, defined as at least 1 measurable lesion > 20 mm by x-ray, ultrasound, or physical exam or ≥ 10 mm (lymph nodes must be ≥ 15 mm in the short axis) by spiral CT scan or physical exam (in the first 260 patients randomized**)

• Measurable lesions that are sole sites of disease must be outside a previous radiotherapy field unless disease progression has been documented NOTE: **Measurable or nonmeasurable disease allowed after the first 260 patients

• No appreciable cavitation in central thoracic lesions

• No untreated brain or meningeal metastases

• Patients with treated and radiologic or clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible provided the metastases are asymptomatic and do not require corticosteroids

• No pleural effusion

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Absolute granulocyte count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Creatinine clearance > 50 mL/min

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT ≤ 2 times ULN (< 5 times ULN if due to liver metastasis)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double-method contraception (barrier method for men)

• No other malignancy within the past 5 years, except in situ cancer, basal cell or squamous cell skin cancer, or malignancy cured by definitive prior therapy alone (e.g., surgery) and continuously disease-free for at least 5 years

• Mean QTc with Bazett correction ≤ 480 msec in screening ECG (at least one value must be ≤ 480 msec when measured automatically or manually corrected using Bazett's or Fridericia's correction)

• No history of familial long QT syndrome

• No untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction including any of the following:

• Unstable angina

• Congestive heart failure

• Myocardial infarction within the past year

• Cardiac ventricular arrhythmias requiring medication

• History of second or third degree atrioventricular conduction defects

• LVEF > 50% in patients with significant cardiac history, even if controlled

• No resting BP consistently > 150 mm Hg systolic and/or > 100 mm Hg diastolic

• No poorly controlled hypertension

• No history of labile hypertension or poor compliance with anti-hypertensive medication

• No overt bleeding (> 30 mL bleeding/episode) from any site within the past 3 months

• No clinically relevant hemoptysis (> 5 mL fresh blood) within the past 4 weeks

• Flecks of blood in sputum allowed

• No active or uncontrolled infections, or serious illnesses or medical conditions which would not permit the patient to be treated according to the study

• No prior allergic reactions to drugs containing Cremophor EL®

• No inflammatory bowel disease (e.g., Crohn disease or ulcerative colitis)

• No documented weight loss > 10% within the past 3 months

• Patients with weight loss 5-10% or whose weight loss status is unknown are eligible provided serum albumin levels are ≥ 30 g/L

• No peripheral neuropathy > grade 1

• Must be fit for combined modality treatment

• Sufficiently fluent and willing to complete quality-of-life questionnaires

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior therapy

• No prior chemotherapy for metastatic or recurrent disease

• No prior anti-angiogenic therapy (e.g., bevacizumab, cediranib, AZD6474, PTK/ZK, sunitinib malate, or other agents considered angiogenesis inhibitors by NCIC Clinical Trials Group for any indication)

• Prior cox-2 inhibitors in standard doses allowed

• At least 12 months since prior adjuvant chemotherapy for completely resected disease

• Combined chemotherapy/radiotherapy regimens for locally advanced stage IIIB disease not allowed

• At least 21 days since prior radiotherapy

• At least 21 days since prior cetuximab or other monoclonal antibodies

• At least 14 days since prior EGFR inhibitor therapy for adjuvant therapy or metastatic disease (e.g., tyrosine kinase inhibitors, vaccines, or other agents considered by NCIC CTG as acting on the EGFR pathway)

• At least 14 days since prior major surgery

• At least 1 week since prior corticosteroids

• No other concurrent experimental drugs, anticancer treatment, or investigational therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto Nacional de Cancer (INCA)	Rio de Janeiro		Brazil	CEP20231-050
2	Instituto de Cancer Arnaldo Vieira de Carvalho	Sao Paulo		Brazil	01224-010
3	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
4	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
5	BCCA - Abbotsford Centre	Abbotsford	British Columbia	Canada	V2S 0C2
6	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia	Canada	V3V 1Z2
7	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
8	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
9	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario	Canada	K7L 5P9
10	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
11	Ottawa Health Research Institute - General Division	Ottawa	Ontario	Canada	K1H 8L6
12	Algoma District Cancer Program	Sault Ste. Marie	Ontario	Canada	P6B 0A8
13	Niagara Health System	St. Catharines	Ontario	Canada	L2R 7C6
14	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5
15	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
16	Windsor Regional Cancer Centre	Windsor	Ontario	Canada	N8W 2X3
17	McGill University - Dept. Oncology	Montreal	Quebec	Canada	H2W 1S6
18	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
19	University Institute of Cardiology and	Quebec		Canada	G1V 4G5

Sponsors and Collaborators

• NCIC Clinical Trials Group

Investigators

• Study Chair: Scott A. Laurie, MD, FRCPC, Ottawa Regional Cancer Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT00795340
• Other Study ID Numbers: BR29; CAN-NCIC-BR29; CDR0000618671
• First Posted: Nov 21, 2008
• Last Update Posted: Oct 8, 2020
• Last Verified: Jun 1, 2015

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by NCIC Clinical Trials Group: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Carboplatin; Cediranib

Study Results

Participant Flow

Arm/Group Title	Cediranib	Placebo
Arm/Group Description	Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. carboplatin: Given IV cediranib maleate: Given orally paclitaxel: Given IV	Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I. carboplatin: Given IV paclitaxel: Given IV placebo: Given orally
Period Title: Overall Study
STARTED	153	153
COMPLETED	146	153
NOT COMPLETED	7	0

Baseline Characteristics

Arm/Group Title	Cediranib	Placebo	Total
Arm/Group Description	Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. carboplatin: Given IV cediranib maleate: Given orally paclitaxel: Given IV	Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I. carboplatin: Given IV paclitaxel: Given IV placebo: Given orally	Total of all reporting groups
Overall Participants	153	153	306
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	62	62
Sex: Female, Male (Count of Participants)
Female	69 45.1%	70 45.8%	139 45.4%
Male	84 54.9%	83 54.2%	167 54.6%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	129 84.3%	132 86.3%	261 85.3%
Hispanic	1 0.7%	2 1.3%	3 1%
Black	1 0.7%	5 3.3%	6 2%
Asian	12 7.8%	9 5.9%	21 6.9%
Aboriginal	1 0.7%	0 0%	1 0.3%
Other	7 4.6%	2 1.3%	9 2.9%
Not Reported	2 1.3%	3 2%	5 1.6%
Region of Enrollment (participants) [Number]
Canada	102 66.7%	98 64.1%	200 65.4%
Brazil	7 4.6%	11 7.2%	18 5.9%
Australia	44 28.8%	44 28.8%	88 28.8%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Medians of survival time, and their confidence intervals.
Time Frame	at every 3 months visit throughout trial, a median of 13.1 months.

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Cediranib	Placebo
Arm/Group Description	Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. carboplatin: Given IV cediranib maleate: Given orally paclitaxel: Given IV	Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I. carboplatin: Given IV paclitaxel: Given IV placebo: Given orally
Measure Participants	153	153
Median (95% Confidence Interval) [months]	12.2	12.1

2. Secondary Outcome

Title	Progression-free Survival
Description	Medians of PFS and their confidence intervals by arm
Time Frame	at every 3 months visit throughout trial, a median of 12 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Cediranib	Placebo
Arm/Group Description	Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. carboplatin: Given IV cediranib maleate: Given orally paclitaxel: Given IV	Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I. carboplatin: Given IV paclitaxel: Given IV placebo: Given orally
Measure Participants	153	153
Median (95% Confidence Interval) [months]	5.52	5.45

3. Secondary Outcome

Title	Objective Tumor Response as Assessed by RECIST Criteria v1.1.
Description	Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.
Time Frame	Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Cediranib	Placebo
Arm/Group Description	Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. carboplatin: Given IV cediranib maleate: Given orally paclitaxel: Given IV	Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I. carboplatin: Given IV paclitaxel: Given IV placebo: Given orally
Measure Participants	153	153
Number (95% Confidence Interval) [percentage of participants]	52 34%	34 22.2%

Adverse Events

Time Frame	from the start of treatment to time of 4 weeks after stopped the treatment.
Arm/Group Title	Cediranib		Placebo
Arm/Group Description	Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.		Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I.
All Cause Mortality
	Cediranib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cediranib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/153 (43.8%)		54/153 (35.3%)
Blood and lymphatic system disorders
Febrile neutropenia	11/153 (7.2%)		7/153 (4.6%)
Hemoglobin	1/153 (0.7%)		3/153 (2%)
Cardiac disorders
Cardiac ischemia/infarction	1/153 (0.7%)		1/153 (0.7%)
Cardiopulmonary arrest	1/153 (0.7%)		0/153 (0%)
Pericardial effusion	0/153 (0%)		1/153 (0.7%)
Supraventricular arrhythmia Atrial fibrillation	0/153 (0%)		1/153 (0.7%)
Supraventricular arrhythmia Sinus tachycardia	0/153 (0%)		1/153 (0.7%)
Endocrine disorders
Hypothyroidism	1/153 (0.7%)		0/153 (0%)
Eye disorders
Blurred vision	0/153 (0%)		1/153 (0.7%)
Gastrointestinal disorders
Constipation	1/153 (0.7%)		2/153 (1.3%)
Diarrhea	7/153 (4.6%)		0/153 (0%)
Mucositis (functional/symptomatic) Oral cavity	0/153 (0%)		1/153 (0.7%)
Nausea	6/153 (3.9%)		5/153 (3.3%)
Obstruction, GI Small bowel NOS	1/153 (0.7%)		0/153 (0%)
Pain Abdomen NOS	3/153 (2%)		0/153 (0%)
Perforation, GI Colon	1/153 (0.7%)		0/153 (0%)
Vomiting	8/153 (5.2%)		5/153 (3.3%)
General disorders
Death Death NOS	1/153 (0.7%)		2/153 (1.3%)
Death Disease progression NOS	6/153 (3.9%)		4/153 (2.6%)
Edema: limb	1/153 (0.7%)		0/153 (0%)
Fatigue	2/153 (1.3%)		1/153 (0.7%)
Fever	0/153 (0%)		5/153 (3.3%)
Pain Chest/thorax NOS	1/153 (0.7%)		4/153 (2.6%)
Hepatobiliary disorders
Pain Liver	0/153 (0%)		1/153 (0.7%)
Immune system disorders
Allergic reaction	0/153 (0%)		3/153 (2%)
Infections and infestations
Colitis, infectious	1/153 (0.7%)		0/153 (0%)
Infection (documented clinically) Blood	1/153 (0.7%)		0/153 (0%)
Infection (documented clinically) Colon	0/153 (0%)		1/153 (0.7%)
Infection (documented clinically) Lung	2/153 (1.3%)		2/153 (1.3%)
Infection (documented clinically) Meninges	1/153 (0.7%)		0/153 (0%)
Infection (documented clinically) Skin	0/153 (0%)		1/153 (0.7%)
Infection (documented clinically) Upper airway NOS	4/153 (2.6%)		0/153 (0%)
Infection with normal ANC Abdomen NOS	2/153 (1.3%)		0/153 (0%)
Infection with normal ANC Anal/perianal	1/153 (0.7%)		0/153 (0%)
Infection with normal ANC Bladder	2/153 (1.3%)		0/153 (0%)
Infection with normal ANC Colon	1/153 (0.7%)		1/153 (0.7%)
Infection with normal ANC Larynx	1/153 (0.7%)		0/153 (0%)
Infection with normal ANC Lung	5/153 (3.3%)		7/153 (4.6%)
Injury, poisoning and procedural complications
Fracture	1/153 (0.7%)		1/153 (0.7%)
Thrombosis/embolism (vascular access)	0/153 (0%)		2/153 (1.3%)
Investigations
Neutrophils	0/153 (0%)		4/153 (2.6%)
Platelets	1/153 (0.7%)		1/153 (0.7%)
cTnI	0/153 (0%)		1/153 (0.7%)
Metabolism and nutrition disorders
Anorexia	2/153 (1.3%)		1/153 (0.7%)
Dehydration	5/153 (3.3%)		3/153 (2%)
Hypoglycemia	1/153 (0.7%)		0/153 (0%)
Hypomagnesemia	1/153 (0.7%)		0/153 (0%)
Hyponatremia	3/153 (2%)		0/153 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness Extremity-lower	1/153 (0.7%)		0/153 (0%)
Muscle weakness Whole body/generalized	0/153 (0%)		1/153 (0.7%)
Pain Back	2/153 (1.3%)		0/153 (0%)
Pain Bone	0/153 (0%)		1/153 (0.7%)
Pain Extremity-limb	1/153 (0.7%)		0/153 (0%)
Pain Muscle	0/153 (0%)		2/153 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain Tumor pain	1/153 (0.7%)		1/153 (0.7%)
Nervous system disorders
CNS hemorrhage	1/153 (0.7%)		0/153 (0%)
CNS ischemia	3/153 (2%)		2/153 (1.3%)
Dizziness	0/153 (0%)		2/153 (1.3%)
Leukoencephalopathy	1/153 (0.7%)		0/153 (0%)
Neuropathy: cranial CN VIII	0/153 (0%)		1/153 (0.7%)
Pain Head/headache	1/153 (0.7%)		0/153 (0%)
Seizure	3/153 (2%)		1/153 (0.7%)
Somnolence	1/153 (0.7%)		0/153 (0%)
Psychiatric disorders
Confusion	3/153 (2%)		1/153 (0.7%)
Renal and urinary disorders
Hemorrhage, GU Urinary NOS	0/153 (0%)		1/153 (0.7%)
Renal failure	1/153 (0.7%)		1/153 (0.7%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/153 (0.7%)		0/153 (0%)
Cough	0/153 (0%)		1/153 (0.7%)
Dyspnea	5/153 (3.3%)		3/153 (2%)
Hemorrhage pulmonary Lung	1/153 (0.7%)		0/153 (0%)
Hiccoughs	0/153 (0%)		1/153 (0.7%)
Pleural effusion	3/153 (2%)		1/153 (0.7%)
Pneumonitis	1/153 (0.7%)		0/153 (0%)
Pneumothorax	1/153 (0.7%)		0/153 (0%)
Vascular disorders
Hemorrhage - Other	1/153 (0.7%)		0/153 (0%)
Hypotension	2/153 (1.3%)		4/153 (2.6%)
Thrombosis/thrombus/embolism	11/153 (7.2%)		12/153 (7.8%)
Other (Not Including Serious) Adverse Events
	Cediranib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	151/153 (98.7%)		152/153 (99.3%)
Blood and lymphatic system disorders
Febrile neutropenia	13/153 (8.5%)		8/153 (5.2%)
Cardiac disorders
Supraventricular arrhythmia Sinus tachycardia	1/153 (0.7%)		8/153 (5.2%)
Ear and labyrinth disorders
Hearing (without monitoring program)	4/153 (2.6%)		8/153 (5.2%)
Eye disorders
Blurred vision	15/153 (9.8%)		11/153 (7.2%)
Gastrointestinal disorders
Constipation	87/153 (56.9%)		101/153 (66%)
Diarrhea	120/153 (78.4%)		56/153 (36.6%)
Dry mouth	7/153 (4.6%)		11/153 (7.2%)
Dysphagia	8/153 (5.2%)		4/153 (2.6%)
Heartburn	28/153 (18.3%)		31/153 (20.3%)
Hemorrhoids	9/153 (5.9%)		3/153 (2%)
Mucositis (clinical exam) Oral cavity	25/153 (16.3%)		15/153 (9.8%)
Mucositis (functional/symptomatic) Oral cavity	36/153 (23.5%)		21/153 (13.7%)
Nausea	102/153 (66.7%)		95/153 (62.1%)
Pain Abdomen NOS	34/153 (22.2%)		27/153 (17.6%)
Vomiting	56/153 (36.6%)		59/153 (38.6%)
General disorders
Edema: limb	21/153 (13.7%)		25/153 (16.3%)
Fatigue	127/153 (83%)		120/153 (78.4%)
Fever	9/153 (5.9%)		22/153 (14.4%)
Flu-like syndrome	11/153 (7.2%)		7/153 (4.6%)
Pain Chest/thorax NOS	38/153 (24.8%)		43/153 (28.1%)
Immune system disorders
Allergic reaction	13/153 (8.5%)		23/153 (15%)
Infections and infestations
Infection with normal ANC Lung	12/153 (7.8%)		8/153 (5.2%)
Infection with normal ANC Upper airway NOS	15/153 (9.8%)		15/153 (9.8%)
Infection with normal ANC Urinary tract NOS	8/153 (5.2%)		11/153 (7.2%)
Infection with unknown ANC Upper airway NOS	10/153 (6.5%)		5/153 (3.3%)
Injury, poisoning and procedural complications
Bruising	8/153 (5.2%)		5/153 (3.3%)
Investigations
Weight loss	35/153 (22.9%)		11/153 (7.2%)
Metabolism and nutrition disorders
Anorexia	93/153 (60.8%)		77/153 (50.3%)
Dehydration	14/153 (9.2%)		11/153 (7.2%)
Hypomagnesemia	12/153 (7.8%)		5/153 (3.3%)
Musculoskeletal and connective tissue disorders
Arthritis	5/153 (3.3%)		8/153 (5.2%)
Muscle weakness Extremity-lower	14/153 (9.2%)		9/153 (5.9%)
Muscle weakness Whole body/generalized	7/153 (4.6%)		10/153 (6.5%)
Pain Back	40/153 (26.1%)		38/153 (24.8%)
Pain Bone	27/153 (17.6%)		27/153 (17.6%)
Pain Chest wall	17/153 (11.1%)		20/153 (13.1%)
Pain Extremity-limb	34/153 (22.2%)		24/153 (15.7%)
Pain Joint	58/153 (37.9%)		67/153 (43.8%)
Pain Muscle	55/153 (35.9%)		75/153 (49%)
Pain Neck	8/153 (5.2%)		8/153 (5.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain Tumor pain	13/153 (8.5%)		19/153 (12.4%)
Nervous system disorders
Dizziness	37/153 (24.2%)		29/153 (19%)
Memory impairment	10/153 (6.5%)		4/153 (2.6%)
Neuropathy-motor	15/153 (9.8%)		9/153 (5.9%)
Neuropathy-sensory	110/153 (71.9%)		110/153 (71.9%)
Pain Head/headache	49/153 (32%)		35/153 (22.9%)
Taste alteration	32/153 (20.9%)		26/153 (17%)
Psychiatric disorders
Confusion	7/153 (4.6%)		10/153 (6.5%)
Insomnia	46/153 (30.1%)		53/153 (34.6%)
Mood alteration Anxiety	27/153 (17.6%)		33/153 (21.6%)
Mood alteration Depression	13/153 (8.5%)		21/153 (13.7%)
Renal and urinary disorders
Urinary frequency	9/153 (5.9%)		1/153 (0.7%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	8/153 (5.2%)		7/153 (4.6%)
Cough	107/153 (69.9%)		108/153 (70.6%)
Dyspnea	104/153 (68%)		92/153 (60.1%)
Hemorrhage pulmonary Lung	8/153 (5.2%)		9/153 (5.9%)
Hemorrhage pulmonary Nose	35/153 (22.9%)		12/153 (7.8%)
Hiccoughs	8/153 (5.2%)		5/153 (3.3%)
Pain Throat/pharynx/larynx	12/153 (7.8%)		12/153 (7.8%)
Rhinitis	11/153 (7.2%)		7/153 (4.6%)
Voice changes	29/153 (19%)		15/153 (9.8%)
Skin and subcutaneous tissue disorders
Alopecia	121/153 (79.1%)		116/153 (75.8%)
Dry skin	19/153 (12.4%)		11/153 (7.2%)
Hand-foot	11/153 (7.2%)		6/153 (3.9%)
Pruritus	12/153 (7.8%)		15/153 (9.8%)
Rash	47/153 (30.7%)		36/153 (23.5%)
Sweating	6/153 (3.9%)		10/153 (6.5%)
Vascular disorders
Hypertension	77/153 (50.3%)		21/153 (13.7%)
Hypotension	8/153 (5.2%)		7/153 (4.6%)
Thrombosis/thrombus/embolism	16/153 (10.5%)		15/153 (9.8%)

Limitations/Caveats

Early termination at phase II part of the trial, leading to small numbers of subjects analyzed, and limited follow up time.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There IS 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.