A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02300987
• Collaborator: (none)
• Enrollment: 10
• Locations: 7
• Arms: 2
• Actual Duration (Months): 35.8
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This was a multi-center, randomized, double blind (investigator and subject), placebo controlled Phase II study to determine the efficacy and safety of treatment with ribociclib versus placebo in subjects with progressive relapsed, refractory incurable teratoma. Eligible subjects were randomized in a 2:1 ratio to ribociclib or placebo.

After discontinuation of study treatment, patients were followed up for safety, disease progression and overall survival.

Condition or Disease	Intervention/Treatment	Phase
Teratoma	Drug: LEE011; Drug: LEE011 Placebo	Phase 2

Detailed Description

Safety follow-up: After discontinuation of study treatment, all subjects were followed for safety for 30 days except in the case of death, loss to follow up, withdrawal of consent, or discontinuation of study treatment to enroll in the ribociclib rollover clinical trial (CLEE011X2X01B).

Disease progression follow-up: Subjects who discontinued study drug for any reasons other than disease progression were followed for efficacy every 8 weeks during the first 12 months. After 12 months, they were followed for every 12 weeks until disease progression, death, discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of consent), the initiation of a new antineoplastic treatment, or until all subjects had been followed for at least 18 months after their first dose of study drug, or early study termination, whichever occurred first.

Survival follow-up: All subjects were followed for survival via a phone call (or during a clinic visit) every 12 weeks and up to one additional time per quarter if a survival update was required to meet safety or regulatory needs. The safety follow-up was carried out until any of the following occurred (whichever occurred first): death, withdrawal of consent, loss to follow-up, at least 18 months had elapsed from when the last subject had started treatment, or when 80% of subjects had died or were lost to follow-up, or early study termination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
• Actual Study Start Date: Feb 26, 2015
• Actual Primary Completion Date: Feb 21, 2018
• Actual Study Completion Date: Feb 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: LEE011 600 mg daily dosing days 1-21 of a 28 day cycle	Drug: LEE011
Placebo Comparator: Placebo Arm 600 mg daily dosing days 1-21 of a 28 day cycle	Drug: LEE011 Placebo

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [At 24 months]

   Date of randomization to the date of the first documented progression or death due to any causeas per RECIST v1.1 (by local investigator assessment). Only includes data prior to cross over. Disease progression follow-up: Subjects who discontinued study drug for any reasons other than disease progression were followed for efficacy every 8 weeks during the first 12 months. After 12 months, they were followed for every 12 weeks until disease progression, death, discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of consent), the initiation of a new antineoplastic treatment, or until all subjects had been followed for at least 18 months after their first dose of study drug, or early study termination, whichever occurred first.

Secondary Outcome Measures

1. Best Overall Response (BOR) [At 24 months]

   as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the subject who experienced SD as best overall response entered the secondary phase and was treated with LEE011 after he experienced progressive disease, following his best Stable Disease response. In this outcome measure 2, only the best overall response is indicated.

2. Overall Response Rate [At 27 months]

   Overall response rate (ORR) = complete response (CR) or partial response (PR). ORR was zero, as there were no CRs or PRs in either of the groups

3. Disease Control Rate (DCR) [At 24 months]

   as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the disease control rate is based on the best overall response described in the outcome measure 2.

4. Overall Survival (OS) [At 27 months]

   Only includes data prior to cross over. OS defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut off, OS was censored at the date of last known date patient alive

5. Overall Survival Rate [1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months]

   as per RECIST v1.1. Only includes data prior to cross over. Kaplan-Meier estimates (%) OS rate [95% CI] at different timepoints. The overall survival rate at 27 month is 72.9% by Kaplan-Meyer (K-M) estimator; the reason that it is not 75% (1-25%) (Overall survival) is because of censoring. When the other 6 patients were censored would impact the survival rate with K-M method as the number of patients at risk after each censor was changed. NA for the 95% CI is indicated when no patient died at the time of assessment, as the CI could not be calculated as per definition. Results are presented as a % calculated on the total number of participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Diagnosis of teratoma for which no additional standard surgical or medical therapy exists

• Patients must have completed at least 1 prior line of chemotherapy for germ cell tumor (except patients who present with primary pure teratoma who need not have received any previous chemotherapy)

• Radiographic progression, defined by RECIST v.1.1, after the last cancer treatment and within 12 weeks prior to enrollment, compared with scans within 1 year of enrollment.

• Availability of an archival or newly obtained tumor sample (collected at diagnosis or progression) with accompanying pathology report

• Meaurable or evaluable extra-cranial disease as defined by RECIST v 1.1

Key Exclusion Criteria:

• Malignant germ cell tumors with mixed histology such as embryonal carcinoma, choriocarcinoma, yolk sac tumor or seminoma. Note - this refers to the histology at the time of enrollment, not the histolgy at the time of initial presentation.

• Pathologic evidence of malignant transformation

• CNS disease unless radiation therapy and/or surgery has been completed and serial evaluation demonstrates stable disease

• Prior treatment with any CDK4/6 inhibitor therapy

• Systemic antineoplastic therapy or any experimental therapy within 3 weeks before the first dose of study drug (6 weeks for prior nitrosoureas, bevacizumab, or mitomycin C)

• Major surgery ≤ 2 weeks or radiotherapy ≤ 4 weeks prior to planned start of study drug or patient has not recovered from major side effects.

• Requirement for treatment with any of the prohibited medications including strong CYP3A inhibitors, strong CYP3A inducers, CYP3A substrates with a narrow therapeutic index, and medications with strong risk of QT prolongation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC Kenneth Norris Comprehensive Cancer Center Oncology Dept	Los Angeles	California	United States	90033
2	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87106
3	Memorial Sloan Kettering Oncology Department.	New York	New York	United States	10017
4	Novartis Investigative Site	Villejuif Cedex		France	94800
5	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
6	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
7	Novartis Investigative Site	Madrid		Spain	28041

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 18, 2017
• Statistical Analysis Plan - Dec 7, 2016

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02300987
• Other Study ID Numbers: CLEE011X2201; 2014-000428-12
• First Posted: Nov 25, 2014
• Last Update Posted: Oct 26, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Teratoma,; Germ Cell tumor,; incurable teratoma,; CDK4/6,; LEE011
• Additional relevant MeSH terms: Teratoma

Study Results

Participant Flow

Recruitment Details	Subjects were randomly assigned to Ribociclib or Placebo in a 2:1 ratio. The 2 subjects from the placebo group (primary phase) entered the secondary treatment phase (cross over) after they experienced disease progression, and were then treated with LEE01. One patient from the LEE arm entered the secondary treatment phase.
Pre-assignment Detail	42 subjects were planned to be included (28 for the LEE011 arm and 14 for the Placebo arm). The study was stopped prematurely with 10 patients randomized and treated in this study (8 in the ribociclib arm, 2 in the placebo arm).

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Period Title: Primary Phase : Prior to Cross-over
STARTED	8	2
COMPLETED	2	0
NOT COMPLETED	6	2
Period Title: Primary Phase : Prior to Cross-over
STARTED	1	2
COMPLETED	0	1
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	LEE011	Placebo Arm	Total
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle	Total of all reporting groups
Overall Participants	8	2	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.3 (6.76)	40.5 (17.68)	33.9 (9.07)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	2 100%	10 100%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	4 50%	1 50%	5 50%
Native American	1 12.5%	0 0%	1 10%
Unknown	3 37.5%	1 50%	4 40%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Date of randomization to the date of the first documented progression or death due to any causeas per RECIST v1.1 (by local investigator assessment). Only includes data prior to cross over. Disease progression follow-up: Subjects who discontinued study drug for any reasons other than disease progression were followed for efficacy every 8 weeks during the first 12 months. After 12 months, they were followed for every 12 weeks until disease progression, death, discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of consent), the initiation of a new antineoplastic treatment, or until all subjects had been followed for at least 18 months after their first dose of study drug, or early study termination, whichever occurred first.
Time Frame	At 24 months

Outcome Measure Data

Analysis Population Description

Full analysis set. After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Measure Participants	8	2
Median (90% Confidence Interval) [Days]	71.4	0.0

2. Secondary Outcome

Title	Best Overall Response (BOR)
Description	as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the subject who experienced SD as best overall response entered the secondary phase and was treated with LEE011 after he experienced progressive disease, following his best Stable Disease response. In this outcome measure 2, only the best overall response is indicated.
Time Frame	At 24 months

Outcome Measure Data

Analysis Population Description

Full analysis set. After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Measure Participants	8	2
Stable Disease (SD)	8 100%	1 50%
Progressive Disease (PD)	0 0%	1 50%

3. Secondary Outcome

Title	Overall Response Rate
Description	Overall response rate (ORR) = complete response (CR) or partial response (PR). ORR was zero, as there were no CRs or PRs in either of the groups
Time Frame	At 27 months

Outcome Measure Data

Analysis Population Description

Full analysis set. After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Measure Participants	8	2
Number (95% Confidence Interval) [percentage of participants]	0 0%	0 0%

4. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the disease control rate is based on the best overall response described in the outcome measure 2.
Time Frame	At 24 months

Outcome Measure Data

Analysis Population Description

Full analysis set. After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Measure Participants	8	2
Number (95% Confidence Interval) [percentage of participants]	100 1250%	50 2500%

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Only includes data prior to cross over. OS defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut off, OS was censored at the date of last known date patient alive
Time Frame	At 27 months

Outcome Measure Data

Analysis Population Description

Full analysis set. After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Measure Participants	8	2
Count of Participants [Participants]	6 75%	1 50%

6. Secondary Outcome

Title	Overall Survival Rate
Description	as per RECIST v1.1. Only includes data prior to cross over. Kaplan-Meier estimates (%) OS rate [95% CI] at different timepoints. The overall survival rate at 27 month is 72.9% by Kaplan-Meyer (K-M) estimator; the reason that it is not 75% (1-25%) (Overall survival) is because of censoring. When the other 6 patients were censored would impact the survival rate with K-M method as the number of patients at risk after each censor was changed. NA for the 95% CI is indicated when no patient died at the time of assessment, as the CI could not be calculated as per definition. Results are presented as a % calculated on the total number of participants.
Time Frame	1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months

Outcome Measure Data

Analysis Population Description

Full analysis set.After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Measure Participants	8	2
1 month	100 1250%	100 5000%
2 months	100 1250%	100 5000%
3 months	100 1250%	100 5000%
6 months	100 1250%	100 5000%
9 months	100 1250%	100 5000%
12 months	87.5 1093.8%	100 5000%
15 months	87.5 1093.8%	100 5000%
18 months	87.5 1093.8%	100 5000%
21 months	87.5 1093.8%	50.0 2500%
24 months	87.5 1093.8%	50.0 2500%
27 months	72.9 911.3%	50.0 2500%

7. Post-Hoc Outcome

Title	All Collected Deaths
Description	On treatment deaths are collected from first patient first visit up to 30 days after study treatment discontinuation (approximately 12 months, median duration of exposure). Patients with cancer are also followed up for overall survival until the end of the trial. During overall survival (up to 27 months after the first patient first visit), additional deaths were recorded, including deaths due to the cancer disease (having occurred more than 30 days after study drug discontinuation)
Time Frame	12 months, 27 months

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	LEE011	Placebo Arm
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle	600 mg daily dosing days 1-21 of a 28 day cycle
Measure Participants	8	2
Total deaths	2 25%	1 50%
Deaths on treatment	0 0%	0 0%
Deaths post treatment survival follow up	2 25%	1 50%

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days.
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Arm/Group Title	LEE011		Placebo		All Patients
Arm/Group Description	600 mg daily dosing days 1-21 of a 28 day cycle		Placebo		All patients
All Cause Mortality
	LEE011		Placebo		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/2 (0%)		0/10 (0%)
Serious Adverse Events
	LEE011		Placebo		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Gastrointestinal disorders
Vomiting	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
General disorders
Fatigue	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Pyrexia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Infections and infestations
Meningitis bacterial	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Pneumonia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Investigations
Blood creatinine increased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Nervous system disorders
Headache	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Renal and urinary disorders
Acute kidney injury	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Vascular disorders
Hypotension	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	LEE011		Placebo		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		1/2 (50%)		9/10 (90%)
Blood and lymphatic system disorders
Anaemia	2/8 (25%)		0/2 (0%)		2/10 (20%)
Leukopenia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Lymphopenia	2/8 (25%)		0/2 (0%)		2/10 (20%)
Neutropenia	4/8 (50%)		0/2 (0%)		4/10 (40%)
Thrombocytopenia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Cardiac disorders
Palpitations	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Congenital, familial and genetic disorders
Dermoid cyst	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Ear and labyrinth disorders
Ear pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Tinnitus	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Gastrointestinal disorders
Abdominal pain	2/8 (25%)		0/2 (0%)		2/10 (20%)
Abdominal pain upper	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Constipation	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Diarrhoea	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Gastrooesophageal reflux disease	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Nausea	5/8 (62.5%)		0/2 (0%)		5/10 (50%)
Stomatitis	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Vomiting	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
General disorders
Asthenia	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Breakthrough pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Chest pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Fatigue	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Impaired healing	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Malaise	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Non-cardiac chest pain	2/8 (25%)		0/2 (0%)		2/10 (20%)
Pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Pyrexia	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Infections and infestations
Anal infection	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Fungal infection	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Laryngitis	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Nasopharyngitis	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Rhinitis	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Urinary tract infection	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Injury, poisoning and procedural complications
Ligament sprain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Procedural pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Thermal burn	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Investigations
Alpha 1 foetoprotein increased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Blood creatine increased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Blood creatinine increased	2/8 (25%)		0/2 (0%)		2/10 (20%)
Haemoglobin decreased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Lymphocyte count decreased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Neutrophil count decreased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Weight decreased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	4/8 (50%)		0/2 (0%)		4/10 (40%)
Dehydration	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Hypercalcaemia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Hyperglycaemia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Back pain	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Muscle tightness	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Muscular weakness	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Musculoskeletal pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Musculoskeletal stiffness	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Myalgia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Nervous system disorders
Dizziness	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Headache	6/8 (75%)		0/2 (0%)		6/10 (60%)
Neuropathy peripheral	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Paraesthesia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Psychiatric disorders
Agitation	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Insomnia	3/8 (37.5%)		0/2 (0%)		3/10 (30%)
Libido decreased	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Renal and urinary disorders
Cystitis noninfective	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Nocturia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)		1/2 (50%)		2/10 (20%)
Dysphonia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Dyspnoea	2/8 (25%)		0/2 (0%)		2/10 (20%)
Pleuritic pain	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Rhinorrhoea	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Skin and subcutaneous tissue disorders
Alopecia	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Night sweats	2/8 (25%)		0/2 (0%)		2/10 (20%)
Rash	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Rash maculo-papular	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Skin lesion	1/8 (12.5%)		0/2 (0%)		1/10 (10%)
Vascular disorders
Hypertension	1/8 (12.5%)		0/2 (0%)		1/10 (10%)

Limitations/Caveats

After 10 patients were included the recruitment was halted for business reasons not for safety concerns. Overall Survival presents all deaths up to 27 months while the all-cause mortality presents deaths up to 30 days after treatment discontinuation

More Information

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 the pooled data (ie, data from all sites) in the clinical trial.