An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01646125
• Collaborator: (none)
• Enrollment: 59
• Locations: 27
• Arms: 2
• Actual Duration (Months): 35.4
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to determine if AUY922 had superior efficacy when compared to chemotherapy agents docetaxel or pemetrexed in patients whose tumor had EGFR mutations.

The primary purpose of this study was to compare the efficacy of AUY922, when administered i.v. on a once-weekly schedule at 70 mg/m2, versus docetaxel or pemetrexed in adult patients with advanced NSCLC, whose tumors harbored EGFR activating mutations, and had developed resistance to EGFR TKI.

Condition or Disease	Intervention/Treatment	Phase
Advanced Non Small Cell Lung Cancer (NSCLC)	Drug: AUY922; Drug: Docetaxel; Drug: Pemetrexed	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations Who Have Progressed on Prior EGFR TKI Treatment
• Actual Study Start Date: Nov 23, 2012
• Actual Primary Completion Date: Nov 4, 2015
• Actual Study Completion Date: Nov 4, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AUY922 arm Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Drug: AUY922; AUY922 was to be given by i.v. once weekly at 70 mg/m2 until disease progression, death or any other reason for discontinuation from study treatment.
Active Comparator: chemotherapy arm Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.	Drug: Docetaxel; Docetaxel was to be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity; Other Names: TAXOTERE ; Drug: Pemetrexed; Pemetrexed was to be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity; Other Names: ALIMTA

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [16 months]

   Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures

1. Overall Response Rate (ORR) [16 months]

   ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all the efficacy assessments was stopped at that time.

2. Overall Survival (OS) [from randomization until death up to death]

   OS is defined as the time from the date of randomization to date of death due to any cause. If a death has not been observed by the date of analysis cutoff, then OS was to be censored at the last known date patient was alive.

3. Disease Control Rate (DCR) [baseline, until disease progression up to 24 months]

   Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1

4. Time to Response (TRR) [baseline, until disease progression up to 24 months]

   TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1

5. Duration of Response (DOR) [baseline, until disease progression up to 24 months]

   The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1

6. Rate of Adverse Events (AEs) [baseline, until disease progression up to 24 months]

   To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.

7. Change in Laboratory Paramenters [baseline, until disease progression up to 24 months]

   Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.

8. Time to Progression (TTP) [baseline, until disease progression up to 24 months]

   TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients with histologically or cytologically documented, locally advanced (stage IIIB who are not amenable to combined modality treatment) or recurrent or metastatic (Stage

1. non-small cell lung cancer.

1. Patients must have EGFR gene mutation in their tumors. This can be source - documented by one of the following:

• Provide a pathology report that indicates the patient's tumor had EGFR activating mutation in the past.

Or:

• Perform testing (local or central) in an archival tumor or a fresh baseline biopsy tumor tissue to show the presence of EGFR activating mutation.

1. Patients must have documented clinical benefit (CR, PR, or patients with SD for 6 months or greater) on prior EGFR TKI (e.g. erlotinib or gefitinib) followed by documented progression according to RECIST.

2. Patients must have received prior platinum containing treatment.

3. WHO performance status of 0-1

Exclusion Criteria:

1. Patients who have received more than two prior lines of antineoplastic therapy for advanced disease. Chemotherapy administered as neoadjuvant or adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study.

2. Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least 2 months and have discontinued high dose corticosteroids will be eligible for protocol participation

3. Prior treatment with an HSP90 inhibitor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.	Los Angeles	California	United States	90048
2	Maryland Oncology Hematology, P.A. SC	Rockville	Maryland	United States	20850
3	University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5	Madison	Wisconsin	United States	53792-6164
4	Novartis Investigative Site	Marseille cedex 20	Bouches Du Rhone	France	13915
5	Novartis Investigative Site	Creteil		France	94000
6	Novartis Investigative Site	Villejuif Cedex		France	94805
7	Novartis Investigative Site	Hong Kong		Hong Kong
8	Novartis Investigative Site	Monza	MB	Italy	20900
9	Novartis Investigative Site	Milano	MI	Italy	20133
10	Novartis Investigative Site	Parma	PR	Italy	43100
11	Novartis Investigative Site	Orbassano	TO	Italy	10043
12	Novartis Investigative Site	Koto ku	Tokyo	Japan	135 8550
13	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
14	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06351
15	Novartis Investigative Site	Seoul	Seocho Gu	Korea, Republic of	06591
16	Novartis Investigative Site	Seoul		Korea, Republic of	03722
17	Novartis Investigative Site	Amsterdam		Netherlands	1081 HV
18	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
19	Novartis Investigative Site	Bergen		Norway	5021
20	Novartis Investigative Site	Oslo		Norway	NO-0424
21	Novartis Investigative Site	Gdansk		Poland	80 952
22	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
23	Novartis Investigative Site	Madrid		Spain	28034
24	Novartis Investigative Site	Kuei-Shan Chiang	Taoyuan/ Taiwan ROC	Taiwan	33305
25	Novartis Investigative Site	Taichung		Taiwan	407
26	Novartis Investigative Site	Taipei		Taiwan	10048
27	Novartis Investigative Site	Leicester		United Kingdom	LE1 5WW

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01646125
• Other Study ID Numbers: CAUY922A2207; 2012-001050-25
• First Posted: Jul 20, 2012
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Novartis Pharmaceuticals: Non-small cell lung carcinoma (NSCLC); treatment of lung cancer after first metastasis; lung cancer; lung adenocarcinoma; Squamous cell lung carcinoma; Large-cell lung carcinoma; Non small cell lung carcinoma; Non small cell lung cancer; Non-small cell lung cancer; NSCLC; Large cell lung carcinoma; Large cell lung cancer; HSP90; AUY922; Pemetrexed; Docetaxel; EGFR TKI; EGFR mutations
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Pemetrexed

Study Results

Participant Flow

Recruitment Details	Patients were randomized in a ratio of 1:1 to receive either AUY922 or pemetrexed/docetaxel. A total of 59 participants were randomized in the study: 31 to the AUY922 arm and 28 to the chemotherapy arm. 2 patients from the AUY922 arm & 5 from the chemotherapy arm were not treated. Only 52 received at least 1 dose of study medication.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Period Title: Overall Study
STARTED	31	28
COMPLETED	0	0
NOT COMPLETED	31	28

Baseline Characteristics

Arm/Group Title	AUY922 Arm	Chemotherapy Arm	Total
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.	Total of all reporting groups
Overall Participants	31	28	59
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.8 (10.10)	62.1 (10.34)	61.9 (10.13)
Sex: Female, Male (Count of Participants)
Female	27 87.1%	21 75%	48 81.4%
Male	4 12.9%	7 25%	11 18.6%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	16 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set (EAS) compromised of a subset of patients in the FAS who received 2 lines of prior antineoplastic therapy consisting of a platinum-based treatment & an EGFR TKI treatment. The DMC recommendation at Interim analysis was to stop the study for futility. As a result, collection of all efficacy assessments was stopped.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	19	17
Median (90% Confidence Interval) [Months]	1.5	2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AUY922 Arm, Chemotherapy Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 90%; 0.35 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all the efficacy assessments was stopped at that time.
Time Frame	16 months

Outcome Measure Data

Analysis Population Description

The data monitoring committee's (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	19	17
Complete Response (CR)	0 0%	0 0%
Partial Response (PR)	3 9.7%	2 7.1%
ORR (CR + PR)	3 9.7%	2 7.1%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from the date of randomization to date of death due to any cause. If a death has not been observed by the date of analysis cutoff, then OS was to be censored at the last known date patient was alive.
Time Frame	from randomization until death up to death

Outcome Measure Data

Analysis Population Description

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	0	0

4. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1
Time Frame	baseline, until disease progression up to 24 months

Outcome Measure Data

Analysis Population Description

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	0	0

5. Secondary Outcome

Title	Time to Response (TRR)
Description	TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1
Time Frame	baseline, until disease progression up to 24 months

Outcome Measure Data

Analysis Population Description

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	0	0

6. Secondary Outcome

Title	Duration of Response (DOR)
Description	The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1
Time Frame	baseline, until disease progression up to 24 months

Outcome Measure Data

Analysis Population Description

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	0	0

7. Secondary Outcome

Title	Rate of Adverse Events (AEs)
Description	To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
Time Frame	baseline, until disease progression up to 24 months

Outcome Measure Data

Analysis Population Description

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	0	0

8. Secondary Outcome

Title	Change in Laboratory Paramenters
Description	Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.
Time Frame	baseline, until disease progression up to 24 months

Outcome Measure Data

Analysis Population Description

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	0	0

9. Secondary Outcome

Title	Time to Progression (TTP)
Description	TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1
Time Frame	baseline, until disease progression up to 24 months

Outcome Measure Data

Analysis Population Description

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Arm/Group Title	AUY922 Arm	Chemotherapy Arm
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Safety set: comprised of all participants who received at least one dose of study medication (AUY922, pemetrexed or docetaxel). In the safety set, patients were classified and analyzed according to the treatment received. Of the 59 participants randomized, only 52 received one dose of study medication.
Arm/Group Title	AUY922 Arm		Chemotherapy Arm		Total
Arm/Group Description	Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.		Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.		Total
All Cause Mortality
	AUY922 Arm		Chemotherapy Arm		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AUY922 Arm		Chemotherapy Arm		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/29 (34.5%)		6/23 (26.1%)		16/52 (30.8%)
Cardiac disorders
ATRIAL FIBRILLATION	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Eye disorders
RETINAL DEGENERATION	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
VISION BLURRED	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Gastrointestinal disorders
CONSTIPATION	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
STOMATITIS	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
General disorders
ASTHENIA	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
DISCOMFORT	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
PYREXIA	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
SUDDEN DEATH	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Infections and infestations
LOCALISED INFECTION	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
PNEUMONIA	1/29 (3.4%)		1/23 (4.3%)		2/52 (3.8%)
UPPER RESPIRATORY TRACT INFECTION	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
URINARY TRACT INFECTION	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Injury, poisoning and procedural complications
FALL	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Metabolism and nutrition disorders
DECREASED APPETITE	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO CENTRAL NERVOUS SYSTEM	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
Nervous system disorders
DIZZINESS	0/29 (0%)		1/23 (4.3%)		1/52 (1.9%)
EPILEPSY	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS	1/29 (3.4%)		0/23 (0%)		1/52 (1.9%)
Other (Not Including Serious) Adverse Events
	AUY922 Arm		Chemotherapy Arm		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/29 (96.6%)		21/23 (91.3%)		49/52 (94.2%)
Blood and lymphatic system disorders
ANAEMIA	5/29 (17.2%)		0/23 (0%)		5/52 (9.6%)
LYMPHOPENIA	2/29 (6.9%)		1/23 (4.3%)		3/52 (5.8%)
NEUTROPENIA	0/29 (0%)		3/23 (13%)		3/52 (5.8%)
Eye disorders
ACCOMMODATION DISORDER	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
NIGHT BLINDNESS	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
PHOTOPSIA	10/29 (34.5%)		0/23 (0%)		10/52 (19.2%)
VISION BLURRED	6/29 (20.7%)		0/23 (0%)		6/52 (11.5%)
VISUAL ACUITY REDUCED	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
VISUAL IMPAIRMENT	6/29 (20.7%)		0/23 (0%)		6/52 (11.5%)
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	2/29 (6.9%)		1/23 (4.3%)		3/52 (5.8%)
CONSTIPATION	6/29 (20.7%)		2/23 (8.7%)		8/52 (15.4%)
DIARRHOEA	21/29 (72.4%)		1/23 (4.3%)		22/52 (42.3%)
DRY MOUTH	1/29 (3.4%)		2/23 (8.7%)		3/52 (5.8%)
NAUSEA	10/29 (34.5%)		3/23 (13%)		13/52 (25%)
STOMATITIS	1/29 (3.4%)		3/23 (13%)		4/52 (7.7%)
VOMITING	3/29 (10.3%)		3/23 (13%)		6/52 (11.5%)
General disorders
ASTHENIA	8/29 (27.6%)		8/23 (34.8%)		16/52 (30.8%)
AXILLARY PAIN	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
FATIGUE	10/29 (34.5%)		5/23 (21.7%)		15/52 (28.8%)
NON-CARDIAC CHEST PAIN	2/29 (6.9%)		1/23 (4.3%)		3/52 (5.8%)
OEDEMA PERIPHERAL	1/29 (3.4%)		2/23 (8.7%)		3/52 (5.8%)
PYREXIA	2/29 (6.9%)		4/23 (17.4%)		6/52 (11.5%)
Hepatobiliary disorders
HEPATOCELLULAR INJURY	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
Infections and infestations
CONJUNCTIVITIS	0/29 (0%)		3/23 (13%)		3/52 (5.8%)
RHINITIS	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
UPPER RESPIRATORY TRACT INFECTION	3/29 (10.3%)		1/23 (4.3%)		4/52 (7.7%)
URINARY TRACT INFECTION	1/29 (3.4%)		2/23 (8.7%)		3/52 (5.8%)
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED	3/29 (10.3%)		0/23 (0%)		3/52 (5.8%)
Metabolism and nutrition disorders
DECREASED APPETITE	4/29 (13.8%)		3/23 (13%)		7/52 (13.5%)
HYPERGLYCAEMIA	3/29 (10.3%)		0/23 (0%)		3/52 (5.8%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	6/29 (20.7%)		0/23 (0%)		6/52 (11.5%)
BACK PAIN	5/29 (17.2%)		3/23 (13%)		8/52 (15.4%)
MUSCULOSKELETAL CHEST PAIN	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
MUSCULOSKELETAL PAIN	5/29 (17.2%)		0/23 (0%)		5/52 (9.6%)
MYALGIA	4/29 (13.8%)		3/23 (13%)		7/52 (13.5%)
PAIN IN EXTREMITY	3/29 (10.3%)		2/23 (8.7%)		5/52 (9.6%)
Nervous system disorders
DIZZINESS	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
HEADACHE	9/29 (31%)		0/23 (0%)		9/52 (17.3%)
PARAESTHESIA	2/29 (6.9%)		2/23 (8.7%)		4/52 (7.7%)
PERIPHERAL SENSORY NEUROPATHY	2/29 (6.9%)		2/23 (8.7%)		4/52 (7.7%)
VISUAL FIELD DEFECT	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
VISUAL PERSEVERATION	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
Psychiatric disorders
DEPRESSION	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
INSOMNIA	3/29 (10.3%)		0/23 (0%)		3/52 (5.8%)
Renal and urinary disorders
POLLAKIURIA	2/29 (6.9%)		0/23 (0%)		2/52 (3.8%)
Respiratory, thoracic and mediastinal disorders
COUGH	7/29 (24.1%)		2/23 (8.7%)		9/52 (17.3%)
DYSPNOEA	2/29 (6.9%)		7/23 (30.4%)		9/52 (17.3%)
HAEMOPTYSIS	0/29 (0%)		2/23 (8.7%)		2/52 (3.8%)
OROPHARYNGEAL PAIN	0/29 (0%)		2/23 (8.7%)		2/52 (3.8%)
Skin and subcutaneous tissue disorders
ALOPECIA	0/29 (0%)		6/23 (26.1%)		6/52 (11.5%)
NAIL DISORDER	0/29 (0%)		2/23 (8.7%)		2/52 (3.8%)
PRURITUS	6/29 (20.7%)		2/23 (8.7%)		8/52 (15.4%)
RASH	2/29 (6.9%)		4/23 (17.4%)		6/52 (11.5%)
Vascular disorders
HYPERTENSION	5/29 (17.2%)		0/23 (0%)		5/52 (9.6%)

Limitations/Caveats

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results to terminate the study early due to futility, data was not collected for this assessment on many of the secondary endpoints.

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Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.