Trial of Vinflunine Versus Alkylating Agent in Metastatic Breast Cancer

• Sponsor: Pierre Fabre Medicament (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01091168
• Collaborator: (none)
• Enrollment: 594
• Locations: 80
• Arms: 2
• Actual Duration (Months): 54
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

In metastatic breast cancer (MBC) patients who have already received anthracyclines, taxanes, antimetabolites and vinca-alkaloids and have developed drug resistance to these drugs, therapeutic options are very limited. Alkylating agents showed a modest activity in pretreated metastatic breast cancer. This phase III trial will compare the effectiveness and the safety profile of vinflunine to an alkylating agent of physician choice in MBC patients who have exhausted anthracyclines, taxanes, antimetabolites and vinca-alkaloids.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Metastases	Drug: vinflunine; Drug: Alkylating agent of physician choice registered in cancer	Phase 3

Detailed Description

Breast cancer is the most frequently diagnosed cancer in women worldwide and the second leading cause of cancer-related deaths in women.

Patients with metastatic breast cancer (MBC) remains incurable, and current goals of therapy are to ameliorate symptoms, delay disease progression, improve or at least maintain quality of life (QoL), and prolong overall survival (OS).There are a number of agents with established single-agent activity, with the anthracyclines and taxanes considered generally the most active. In addition, several drugs with different mechanisms of action such as antimetabolites and vinca-alkaloids have also demonstrated substantial activity in the metastatic setting as single-agents or in combination.

In patients who progress after having received anthracyclines, taxanes, antimetabolites and vinca- alkaloids, therapeutic options are scarce. In this heavily pretreated population for whom overall survival is not expected to exceed 6 to 7 months, there is a clear need for novel therapies.

Vinflunine (VFL) is a microtubule inhibitor obtained by semi-synthesis, interacts with tubulin at the vinca-binding domain and inhibits tubulin assembly by perturbing microtubule dynamics and mitotic spindles without affecting assembled microtubules. VFL antitumour activity was fully demonstrated against a large and varied panel of murine and xenograft models.

The main haematological toxicity reported was the neutropenia Grade 3-4 (40-50%). The incidence of its complications (febrile neutropenia and neutropenic infection) was less than 8%. The main non-haematological toxicity Grade 3-4 (with an incidence more than 10%) reported were constipation and fatigue.

This was a prospective multicentre, open-label, randomised (1:1), phase III study comparing OS in patients treated with vinflunine versus those treated with an alkylating agent of physician's choice as third line treatment or more for patients with locally recurrent and/or metastatic breast cancer previously treated with and no longer candidate to anthracyclines, antimetabolites, taxanes and vinca- alkaloids..

The primary endpoint for the trial was OS. Patients were assessed for toxicity, tumour response and progression and status (alive-dead) at regular intervals during the study treatment and the follow-up period. Patients were treated until disease progression, unacceptable toxicity, patient or investigator's decision. After the study treatment discontinuation, patients were followed until death.

The VFL dose of 280 mg/m² was the selected dose for this phase III study in patients with heavily pre- treated MBC. Indeed, VFL dose was reduced from 320 to 280 mg/m² in advanced transitional cell carcinoma of urothelial tract patients with performance status (PS) of 1 or with PS of 0 and having received prior pelvic irradiation. This dose was more regularly tolerable in patients with advanced disease stage who were heavily pre-treated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 594 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Trial of IV Vinflunine Versus an Alkylating Agent in Patients With Metastatic Breast Cancer Previously Treated With or Resistant to an Anthracycline, a Taxane, an Antimetabolite, and a Vinca-alkaloid (Study L00070 IN 308 B0)
• Actual Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Aug 27, 2012
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: arm A: Vinflunine Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.	Drug: vinflunine; 280 mg/m2 on day 1 of each cycle every 3 weeks; Other Names: JAVLOR L00070
Active Comparator: arm B: Alkylating agent of physician choice Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.	Drug: Alkylating agent of physician choice registered in cancer; cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin; Other Names: Various

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From baseline up to 3 years 1 month]

   The main endpoint of this study is overall survival defined as the time from randomisation to the date of death or last follow-up. For patients who have not died, survival duration will be censored at the date of last contact or last follow-up or the date of last news.

Secondary Outcome Measures

1. Disease Control Rate (DCR) [From baseline up to 3 years 1 month]

   DCR was defined as the proportion of patients with Complete Response (CR), Partial Response (PR) and stable disease (SD), relative to the total number of patients in the analysed population.

2. Progression Free Survival (PFS) [From baseline to cut-off date(27 August 2012), up to 3 years]

   PFS was defined as the time from randomisation to the first tumour progression or death due to any cause in the absence of previous documentation of objective tumour progression. PFS was performed in the ITT and eligible populations every 6 weeks based on RECIST version 1.1. For patients lost of follow up, or without a known record of progression or death, PFS was censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression which ever occured last.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:(main conditions)

• Female patients 18 to 75 years of age with metastatic breast cancer histologically/cytologically confirmed not amenable to curative surgery or radiotherapy and who have received at least two prior chemotherapy regimens including anthracyclines,taxanes,antimetabolite and vinca-alkaloid and are no longer candidate for these drugs,

• Karnofsky performance score of at least 70 %, adequate haematological, hepatic and renal functions and ECG without clinically relevant abnormality.

Exclusion Criteria:

• Concurrent serious uncontrolled medical disorder,

• known or clinical evidence of brain metastases or leptomeningeal involvement,

• pulmonary lymphangitis or symptomatic pleural effusion or symptomatic ascites,

• history of second primary malignancy,

• HIV infection, preexisting neuropathy,

• pregnancy or breast feeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Buenos aires		Argentina
2		Quilmes		Argentina
3		Rosario		Argentina
4		San Martin		Argentina
5		Tucuman		Argentina
6		Graz		Austria
7		Salzburg		Austria
8		Vienna		Austria
9		Gomel		Belarus
10		Grodno		Belarus
11		Minsk		Belarus
12		Vitebsk		Belarus
13		Brussels		Belgium
14		Haine Saint Paul		Belgium
15		Yvoir		Belgium
16		Angers		France
17		Brest		France
18		Clermont Ferrand		France
19		Dijon		France
20		Grenoble		France
21		Le Mans		France
22		Lille		France
23		Limoges		France
24		Lorient		France
25		Montpellier		France
26		Nancy		France
27		Nantes		France
28		Nice		France
29		Paris		France
30		Pontoise		France
31		Reims		France
32		Rouen		France
33		Saint Brieuc		France
34		Saint Priest en Jarez		France
35		Strasbourg		France
36		Berlin		Germany
37		Dortmund		Germany
38		Essen		Germany
39		Mainz		Germany
40		Munich		Germany
41		Trier		Germany
42		Ancona		Italy
43		Aviano		Italy
44		Bolzano		Italy
45		Brindisi		Italy
46		Frattamaggiore		Italy
47		Macerata		Italy
48		Orbassano		Italy
49		Lisboa		Portugal
50		Arkhangelsk		Russian Federation
51		Engels		Russian Federation
52		Moscow		Russian Federation
53		Ryazan		Russian Federation
54		Saratov		Russian Federation
55		St Petersburg		Russian Federation
56		Stavropol		Russian Federation
57		Tambov		Russian Federation
58		Ufa		Russian Federation
59		Volgograd		Russian Federation
60		Durban		South Africa
61		Johannesburg		South Africa
62		Pretoria		South Africa
63		A coruna		Spain
64		Barcelona		Spain
65		Madrid		Spain
66		Sevilla		Spain
67		Taichung		Taiwan
68		Taipei		Taiwan
69		Taoyuan		Taiwan
70		Dnipropetrovsk		Ukraine
71		Kharkiv		Ukraine
72		Khmelnytskyi		Ukraine
73		Kyiv		Ukraine
74		Burnley		United Kingdom
75		Cornwell		United Kingdom
76		Derby		United Kingdom
77		Glasgow		United Kingdom
78		Ipswich		United Kingdom
79		Preston		United Kingdom
80		Worthing		United Kingdom

Sponsors and Collaborators

• Pierre Fabre Medicament

Investigators

• Study Director: Karim Keddad, MD, PhD, Institut de Recherche Pierre Fabre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pierre Fabre Medicament
• ClinicalTrials.gov Identifier: NCT01091168
• Other Study ID Numbers: L00070 IN 308 B0
• First Posted: Mar 23, 2010
• Last Update Posted: Sep 16, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Breast Neoplasms; Alkylating Agents

Study Results

Participant Flow

Arm/Group Title	Vinflunine (VFL)	Alkylating Agent
Arm/Group Description	Patients randomised in the test arm (arm A) received Vinflunine at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Period Title: Overall Study
STARTED	298	296
COMPLETED	0	0
NOT COMPLETED	298	296

Baseline Characteristics

Arm/Group Title	Arm A: Vinflunine	Arm B: Alkylating Agent of Physician Choice	Total
Arm/Group Description	Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin	Total of all reporting groups
Overall Participants	298	296	594
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	236 79.2%	227 76.7%	463 77.9%
>=65 years	62 20.8%	69 23.3%	131 22.1%
Sex: Female, Male (Count of Participants)
Female	298 100%	296 100%	594 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	The main endpoint of this study is overall survival defined as the time from randomisation to the date of death or last follow-up. For patients who have not died, survival duration will be censored at the date of last contact or last follow-up or the date of last news.
Time Frame	From baseline up to 3 years 1 month

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Vinflunine	Alkylating Agent
Arm/Group Description	Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Measure Participants	298	296
Median (95% Confidence Interval) [Months]	9.1	9.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vinflunine, Alkylating Agent
	Comments	Kaplan-Meier curves and life tables by treatment arm were provided. Confidence intervals on the median were calculated using the Brookmeyer and Crowley method. Hazard ratio and 95% confidence intervals were reported. A stratified Cox proportional model was performed to compare the two treatment arms taking into account the stratification factors (except centre) used at the time of randomisation.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.673
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	DCR was defined as the proportion of patients with Complete Response (CR), Partial Response (PR) and stable disease (SD), relative to the total number of patients in the analysed population.
Time Frame	From baseline up to 3 years 1 month

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Vinflunine	Alkylating Agent
Arm/Group Description	Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Measure Participants	298	296
Number (95% Confidence Interval) [Percentage of participants]	43.6 14.6%	35.5 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vinflunine, Alkylating Agent
	Comments	The disease control rate (DCR) were compared in the ITT population and in the population evaluable for response between the 2 arms with a cochran Mantel Haenszel, stratified on WHO performance status at baseline, number of prior chemotherapy lines for the treatment of disease and disease measurability at Baseline.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0424
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time from randomisation to the first tumour progression or death due to any cause in the absence of previous documentation of objective tumour progression. PFS was performed in the ITT and eligible populations every 6 weeks based on RECIST version 1.1. For patients lost of follow up, or without a known record of progression or death, PFS was censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression which ever occured last.
Time Frame	From baseline to cut-off date(27 August 2012), up to 3 years

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Vinflunine	Alkylating Agent
Arm/Group Description	Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Measure Participants	298	296
Median (95% Confidence Interval) [Months]	2.5	1.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vinflunine, Alkylating Agent
	Comments	PFS was compared between the 2 treatment arms by the log-rank test procedure with the 5 % significant level, stratified on the stratification factors (except study site) as specified at the time of randomisation. Os was analysed using Kaplan-Meir method and summarized with median and 95% CI of the median
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4927
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm).
Adverse Event Reporting Description	The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT >=1%)
Arm/Group Title	Vinflunine		Alkylating Agent
Arm/Group Description	Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks		Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
All Cause Mortality
	Vinflunine		Alkylating Agent
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	276/298 (92.6%)		274/296 (92.6%)
Serious Adverse Events
	Vinflunine		Alkylating Agent
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/297 (27.6%)		66/290 (22.8%)
Blood and lymphatic system disorders
Neutropenia	6/297 (2%)		0/290 (0%)
Anaemia	6/297 (2%)		0/290 (0%)
Febrile neutropenia	3/297 (1%)		1/290 (0.3%)
Thrombocytopenia	1/297 (0.3%)		2/290 (0.7%)
Endocardititis staphylococcal	1/297 (0.3%)		0/290 (0%)
Cardiac disorders
Arteriospasm coronary	1/297 (0.3%)		0/290 (0%)
Atrial fibrillation	1/297 (0.3%)		1/290 (0.3%)
Cardiac failure	0/297 (0%)		1/290 (0.3%)
Gastrointestinal disorders
Constipation	5/297 (1.7%)		0/290 (0%)
Vomiting	6/297 (2%)		3/290 (1%)
Abdominal pain	4/297 (1.3%)		1/290 (0.3%)
Ileus	3/297 (1%)		0/290 (0%)
Ileus paralytic	3/297 (1%)		0/290 (0%)
Stomatis	3/297 (1%)		0/290 (0%)
Intestinal obstruction	2/297 (0.7%)		0/290 (0%)
Nausea	2/297 (0.7%)		1/290 (0.3%)
Haematemesis	1/297 (0.3%)		0/290 (0%)
Abdominal pain upper	1/297 (0.3%)		0/290 (0%)
Dysphagia	0/297 (0%)		1/290 (0.3%)
Oesophagial stenosis	0/297 (0%)		1/290 (0.3%)
Upper gastrointestinal haemorrage	1/297 (0.3%)		0/290 (0%)
General disorders
Asthenia	2/297 (0.7%)		0/290 (0%)
Fatigue	2/297 (0.7%)		0/290 (0%)
Femur fracture	1/297 (0.3%)		1/290 (0.3%)
Hepatobiliary disorders
Hepatic function abnormal	1/297 (0.3%)		0/290 (0%)
Bile duct obstruction	0/297 (0%)		1/290 (0.3%)
Infections and infestations
Neutropenic infections	4/297 (1.3%)		1/290 (0.3%)
Pneumonia	3/297 (1%)		1/290 (0.3%)
Urinary tract infection	2/297 (0.7%)		2/290 (0.7%)
Sepsis	1/297 (0.3%)		1/290 (0.3%)
Cellulitis	1/297 (0.3%)		0/290 (0%)
Influenza	1/297 (0.3%)		0/290 (0%)
Staphylococcal infection	1/297 (0.3%)		0/290 (0%)
Catheter related infections	0/297 (0%)		1/290 (0.3%)
Central line infection	0/297 (0%)		1/290 (0.3%)
Lobar pneumonia	0/297 (0%)		1/290 (0.3%)
Upper respiratory tract infection	0/297 (0%)		1/290 (0.3%)
Injury, poisoning and procedural complications
Humerus fracture	1/297 (0.3%)		0/290 (0%)
Allergic transfusion reaction	0/297 (0%)		1/290 (0.3%)
Fall	0/297 (0%)		1/290 (0.3%)
Investigations
Transaminases increased	1/297 (0.3%)		0/290 (0%)
Metabolism and nutrition disorders
Hyponatraemia	2/297 (0.7%)		0/290 (0%)
Hyperglycaemia	1/297 (0.3%)		1/290 (0.3%)
Hypercalcaemia	0/297 (0%)		1/290 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/297 (0.3%)		1/290 (0.3%)
Myalgia	1/297 (0.3%)		0/290 (0%)
Bone pain	0/297 (0%)		1/290 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	38/297 (12.8%)		43/290 (14.8%)
Cancer pain	1/297 (0.3%)		0/290 (0%)
Squamous cell carcinoma	0/297 (0%)		1/290 (0.3%)
Nervous system disorders
Epilepsy	1/297 (0.3%)		0/290 (0%)
Neuralgia	1/297 (0.3%)		0/290 (0%)
Brachial plexopathy	0/297 (0%)		1/290 (0.3%)
Headache	0/297 (0%)		1/290 (0.3%)
Peripheral sensory neuropathy	1/297 (0.3%)		0/290 (0%)
Spinal cord compression	0/297 (0%)		1/290 (0.3%)
Psychiatric disorders
Confusional state	1/297 (0.3%)		0/290 (0%)
Hallucination	0/297 (0%)		1/290 (0.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	4/297 (1.3%)		2/290 (0.7%)
Dyspnoea	6/297 (2%)		2/290 (0.7%)
Interstitial lung disease	0/297 (0%)		1/290 (0.3%)
Pleural effusion	1/297 (0.3%)		1/290 (0.3%)
Acute respiratory failure	1/297 (0.3%)		0/290 (0%)
Pneumonitis	1/297 (0.3%)		0/290 (0%)
Pulmonary hypertension	1/297 (0.3%)		0/290 (0%)
Other (Not Including Serious) Adverse Events
	Vinflunine		Alkylating Agent
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	197/297 (66.3%)		262/290 (90.3%)
Blood and lymphatic system disorders
Neutropenia	37/297 (12.5%)		31/290 (10.7%)
Thrombocyotopenia	3/297 (1%)		39/290 (13.4%)
Gastrointestinal disorders
Constipation	102/297 (34.3%)		23/290 (7.9%)
Nausea	70/297 (23.6%)		67/290 (23.1%)
Abdominal pain	66/297 (22.2%)		16/290 (5.5%)
Stomatitis	52/297 (17.5%)		18/290 (6.2%)
Vomiting	34/297 (11.4%)		33/290 (11.4%)
Diarrhoea	16/297 (5.4%)		19/290 (6.6%)
General disorders
Asthenia	89/297 (30%)		43/290 (14.8%)
Injection site reaction	29/297 (9.8%)		2/290 (0.7%)
Fatigue	23/297 (7.7%)		25/290 (8.6%)
Investigations
Weight decreased	26/297 (8.8%)		17/290 (5.9%)
Metabolism and nutrition disorders
Anorexia	31/297 (10.4%)		24/290 (8.3%)
Musculoskeletal and connective tissue disorders
Myalgia	38/297 (12.8%)		5/290 (1.7%)
Arthralgia	21/297 (7.1%)		3/290 (1%)
Nervous system disorders
Peripheral sensory neuropathy	21/297 (7.1%)		5/290 (1.7%)
Skin and subcutaneous tissue disorders
Alopecia	30/297 (10.1%)		9/290 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

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.