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Treatment of Patients With RAD001 With Progressive Sarcoma

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00767819
Collaborator
(none)
71
Enrollment
6
Locations
3
Arms
109.5
Actual Duration (Months)
11.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this multicenter, three-arm, exact binomial single-stage, phase II trial is to determine the preliminary efficacy and safety of RAD001 in patients with histological evidence of progressive or metastatic bone or soft tissue sarcoma.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
71 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multicenter, Triple-arm, Single-stage, Phase II Trial to Determine the Preliminary Efficacy and Safety of RAD001 in Patients With Histological Evidence of Progressive or Metastatic Bone or Soft Tissue Sarcomas
Actual Study Start Date :
Mar 31, 2008
Actual Primary Completion Date :
May 17, 2017
Actual Study Completion Date :
May 17, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1

Progressive or metastatic bone or soft tissue sarcomas

Drug: Everolimus
2.5 and 5 mg tablets taken orally and starting dose was 10 mg daily for all patients
Other Names:
  • RAD001

    		•
    Experimental: Arm 2

    Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line

    Drug: Everolimus
    2.5 and 5 mg tablets taken orally and starting dose was 10 mg daily for all patients
    Other Names:
  • RAD001

    		•
    Experimental: Arm 3

    Progressive or metastatic alveolar soft part sarcoma (ASPS)

    Drug: Everolimus
    2.5 and 5 mg tablets taken orally and starting dose was 10 mg daily for all patients
    Other Names:
  • RAD001

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Best Overall Response Rates by Week 16 (ITT) [Baseline up to 16 weeks]

      The best overall response is the best response recorded from treatment start until disease progression/recurrence (both measurement and confirmation criteria). Best lesion response was defined by (Resist Criteria V1 for target and non-target lesions): Complete Response (CR)=at least two determinations of CR 4 weeks apart before progression, Partial Response (PR)=at least two determinations of CR 4 weeks apart before progression (and not qualifying for a CR), Stable Disease (SD)=at least one SD assessment >6 weeks after start of treatment and Progressive Disease (PD)=Progression or death due to underlying cancer ≤16 weeks after start of treatment. PD without radiologic evidence were classified as progression only, when clear evidence of clinical deterioration was available and patient discontinued due to "disease progression". Unknown (UNK) = all other cases.

    Secondary Outcome Measures

    1. Objective Tumor Response Rates (Complete Response and Partial Response) at Week 16 (ITT) [Baseline up to approximately 16 weeks]

      The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Best lesion response was defined by (Resist Criteria V1 for target and non-target lesions).

    2. Percentage of Participants With Duration of Response (CR, PR, SD) at 16 Weeks. [Baseline up to 16 weeks]

      Duration of response (CR, PR or SD) applied only to those patients whose best overall response was CR, PR or SD based on local radiologic assessments and was defined as the time from start of treatment to progression or death from underlying disease. Patients not experiencing progression or death at 16 weeks were censored with the date of their last tumor assessment. Duration of response was explored using the Kaplan-Meier method.

    3. Percentage of Participants With Progression-free Survival (PFS) at 16 Weeks [16 weeks]

      Progression-free Survival (PFS) was defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death from any cause. If a patient had not had an event, PFS was censored at the date of the last adequate tumor assessment at week 16

    4. Time to Progression (TTP) (ITT) [Baseline up to 16 weeks]

      Time to progression (TTP) was defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death from underlying disease. If a patient had not had an event, TTP was censored at the date of the last adequate tumor assessment, which was the date of Visit 6 (Week 16) for the core phase and the last available tumor assessment for the follow-up phase. TTP was explored by using the Kaplan-Meier method.

    5. Percentage of Participants With Overall Survival (OS) at Week 16 (ITT) [Baseline up to 16 weeks]

      Overall survival (OS) was defined as the time from the date of start of treatment to death from any cause. If a patient was not known to have died (was alive), OS was censored at the date of the last contact, which was the date of Visit 6 (Week 16) for the core phase and the last available visit for the follow-up phase. OS was explored by using the Kaplan-Meier method. One death occurred in Arm 3 after Week 16.

    Eligibility Criteria

    Criteria

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

    Histological evidence of progressive or metastatic bone or soft tissue sarcoma.

    The following tumor types are included:

    • malignant fibrous histiocytoma

    • liposarcoma

    • synovial sarcoma

    • malignant paraganglioma

    • fibrosarcoma

    • leiomyosarcoma

    • angiosarcoma including haemangiopericytoma

    • malignant peripheral nerve sheath tumor

    • STS, not otherwise specified

    • miscellaneous sarcoma including mixed mesodermal tumors of the uterus

    • osteosarcoma

    • Ewing's sarcoma

    • rhabdomyosarcoma

    • gastrointestinal stromal tumor (only after failure or intolerance of imatinib or sunitinib in 1st and 2nd line)

    • alveolar soft part sarcoma (ASPS)

    • Objective progression of disease may be documented by RECIST criteria. Any of the following would be sufficient according to RECIST:

    • a 20% increase in the sum of unidimensionally measured target lesions

    • a new lesion

    • unequivocal increase in non-measurable disease.

    • Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent.

    • ECOG performance status 0 - 2.

    Exclusion Criteria:

    Anticancer therapy within 3 weeks of enrollment including chemotherapy, hormonal therapy, immunotherapy, or radiotherapy.

    • The following tumor types will not be included:

    • gastrointestinal stromal tumor (except for patients after treatment with imatinib or sunitinib in 1st and 2nd line)

    • chondrosarcoma

    • malignant mesothelioma

    • neuroblastoma.

    • Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus).

    • Neurotoxicity > grade 2 CTC.

    • Radiation of the lung.

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Bad Saarow Germany 15526
    2 Novartis Investigative Site Duesseldorf Germany 40479
    3 Novartis Investigative Site Essen Germany 45147
    4 Novartis Investigative Site Mannheim Germany 68167
    5 Novartis Investigative Site Muenchen Germany 81377
    6 Novartis Investigative Site Milano MI Italy 20133

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00767819
    Other Study ID Numbers:
    • CRAD001C24114
    • 2007-005294-60
    First Posted:
    Oct 7, 2008
    Last Update Posted:
    Apr 1, 2019
    Last Verified:
    Dec 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    progressive GIST
    progressive sarcoma
    Additional relevant MeSH terms:
    Sarcoma
    Everolimus

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Seventy-four patients were screened and seventy-one enrolled.
    Arm/Group Title Arm 1 Arm 2 Arm 3
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    Period Title: Overall Study
    STARTED 37 24 10
    Intent to Treat (ITT) Analysis Set 37 24 10
    Safety Analysis Set (SAF) 37 24 10
    COMPLETED 12 5 10
    NOT COMPLETED 25 19 0

    Baseline Characteristics

    Arm/Group Title Arm 1 Arm 2 Arm 3 Total
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS) Total of all reporting groups
    Overall Participants 37 24 10 71
    Age, Customized (Count of Participants)
    < 65 years
    31
    83.8%
    14
    58.3%
    9
    90%
    54
    76.1%
    >= 65 years
    6
    16.2%
    10
    41.7%
    1
    10%
    17
    23.9%
    Sex: Female, Male (Count of Participants)
    Female
    14
    37.8%
    11
    45.8%
    6
    60%
    31
    43.7%
    Male
    23
    62.2%
    13
    54.2%
    4
    40%
    40
    56.3%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    36
    97.3%
    24
    100%
    10
    100%
    70
    98.6%
    Black
    1
    2.7%
    0
    0%
    0
    0%
    1
    1.4%

    Outcome Measures

    1. Primary Outcome
    Title Best Overall Response Rates by Week 16 (ITT)
    Description The best overall response is the best response recorded from treatment start until disease progression/recurrence (both measurement and confirmation criteria). Best lesion response was defined by (Resist Criteria V1 for target and non-target lesions): Complete Response (CR)=at least two determinations of CR 4 weeks apart before progression, Partial Response (PR)=at least two determinations of CR 4 weeks apart before progression (and not qualifying for a CR), Stable Disease (SD)=at least one SD assessment >6 weeks after start of treatment and Progressive Disease (PD)=Progression or death due to underlying cancer ≤16 weeks after start of treatment. PD without radiologic evidence were classified as progression only, when clear evidence of clinical deterioration was available and patient discontinued due to "disease progression". Unknown (UNK) = all other cases.
    Time Frame Baseline up to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 1 Arm 2 Arm 3
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    Measure Participants 37 24 10
    Complete Response
    0
    0%
    0
    0%
    0
    0%
    Partial Response
    0
    0%
    0
    0%
    0
    0%
    Stable Disease
    40.5
    109.5%
    33.3
    138.8%
    100.0
    1000%
    Progressive Disease
    51.4
    138.9%
    62.5
    260.4%
    0
    0%
    Unknown
    8.1
    21.9%
    4.2
    17.5%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1, Arm 2, Arm 3
    Comments
    Type of Statistical Test Superiority
    Comments The lower limit of the confidence interval was used to support the decision in favor of p0 or p1: if the lower limit of the confidence interval overlapped p0, the hypothesis that p is greater than or equal to p1 could be rejected; on the other side, if the lower limit of the confidence interval excluded p0, the hypothesis that p is greater than or equal to p1 could be accepted.
    Statistical Test of Hypothesis p-Value 0.1
    Comments
    Method Clopper-Person confidence interval
    Comments
    Method of Estimation Estimation Parameter percentage of participants
    Estimated Value 40.5
    Confidence Interval (2-Sided) 80%
    29.5 to 52.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Objective Tumor Response Rates (Complete Response and Partial Response) at Week 16 (ITT)
    Description The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Best lesion response was defined by (Resist Criteria V1 for target and non-target lesions).
    Time Frame Baseline up to approximately 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 1 Arm 2 Arm 3
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    Measure Participants 37 24 10
    Complete response
    0
    0%
    0
    0%
    0
    0%
    Partial response
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Percentage of Participants With Duration of Response (CR, PR, SD) at 16 Weeks.
    Description Duration of response (CR, PR or SD) applied only to those patients whose best overall response was CR, PR or SD based on local radiologic assessments and was defined as the time from start of treatment to progression or death from underlying disease. Patients not experiencing progression or death at 16 weeks were censored with the date of their last tumor assessment. Duration of response was explored using the Kaplan-Meier method.
    Time Frame Baseline up to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 1 Arm 2 Arm 3
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    Measure Participants 15 8 10
    Number [percentage of participants]
    60
    162.2%
    62.5
    260.4%
    100
    1000%
    4. Secondary Outcome
    Title Percentage of Participants With Progression-free Survival (PFS) at 16 Weeks
    Description Progression-free Survival (PFS) was defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death from any cause. If a patient had not had an event, PFS was censored at the date of the last adequate tumor assessment at week 16
    Time Frame 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 1 Arm 2 Arm 3
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    Measure Participants 37 24 10
    Number [percentage of participants]
    35.1
    94.9%
    30.5
    127.1%
    100.0
    1000%
    5. Secondary Outcome
    Title Time to Progression (TTP) (ITT)
    Description Time to progression (TTP) was defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death from underlying disease. If a patient had not had an event, TTP was censored at the date of the last adequate tumor assessment, which was the date of Visit 6 (Week 16) for the core phase and the last available tumor assessment for the follow-up phase. TTP was explored by using the Kaplan-Meier method.
    Time Frame Baseline up to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 1 Arm 2 Arm 3
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    Measure Participants 37 24 10
    Median (95% Confidence Interval) [days]
    57
    57
    499
    6. Secondary Outcome
    Title Percentage of Participants With Overall Survival (OS) at Week 16 (ITT)
    Description Overall survival (OS) was defined as the time from the date of start of treatment to death from any cause. If a patient was not known to have died (was alive), OS was censored at the date of the last contact, which was the date of Visit 6 (Week 16) for the core phase and the last available visit for the follow-up phase. OS was explored by using the Kaplan-Meier method. One death occurred in Arm 3 after Week 16.
    Time Frame Baseline up to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 1 Arm 2 Arm 3
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    Measure Participants 37 24 10
    Number [percentage of participants]
    68.8
    185.9%
    56.9
    237.1%
    100.0
    1000%

    Adverse Events

    Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 16 weeks
    Adverse Event Reporting Description
    Arm/Group Title Arm I Arm II Arm III
    Arm/Group Description Progressive or metastatic bone or soft tissue sarcomas Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line Progressive or metastatic alveolar soft part sarcoma (ASPS)
    All Cause Mortality
    Arm I Arm II Arm III
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/37 (21.6%) 4/24 (16.7%) 1/10 (10%)
    Serious Adverse Events
    Arm I Arm II Arm III
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/37 (40.5%) 14/24 (58.3%) 8/10 (80%)
    Blood and lymphatic system disorders
    ANAEMIA 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    LYMPHOPENIA 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    PANCYTOPENIA 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    Cardiac disorders
    ATRIAL FLUTTER 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    PERICARDIAL EFFUSION 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    Gastrointestinal disorders
    ABDOMINAL PAIN 1/37 (2.7%) 3/24 (12.5%) 0/10 (0%)
    COLITIS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    DIARRHOEA 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    NAUSEA 1/37 (2.7%) 1/24 (4.2%) 0/10 (0%)
    SUBILEUS 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    VOMITING 1/37 (2.7%) 3/24 (12.5%) 0/10 (0%)
    General disorders
    ASTHENIA 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    CHEST PAIN 0/37 (0%) 0/24 (0%) 1/10 (10%)
    DISEASE PROGRESSION 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    FATIGUE 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    GENERAL PHYSICAL HEALTH DETERIORATION 6/37 (16.2%) 5/24 (20.8%) 1/10 (10%)
    LOCALISED OEDEMA 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    OEDEMA PERIPHERAL 1/37 (2.7%) 1/24 (4.2%) 0/10 (0%)
    PAIN 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    PYREXIA 2/37 (5.4%) 1/24 (4.2%) 1/10 (10%)
    Hepatobiliary disorders
    JAUNDICE 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    Infections and infestations
    INFECTION 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    PERITONITIS BACTERIAL 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    PNEUMONIA 3/37 (8.1%) 0/24 (0%) 1/10 (10%)
    SEPSIS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    SUPERINFECTION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    URINARY TRACT INFECTION 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    Injury, poisoning and procedural complications
    BONE CONTUSION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    JAW FRACTURE 0/37 (0%) 0/24 (0%) 1/10 (10%)
    LUMBAR VERTEBRAL FRACTURE 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    WEIGHT DECREASED 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    Metabolism and nutrition disorders
    DECREASED APPETITE 0/37 (0%) 1/24 (4.2%) 1/10 (10%)
    DEHYDRATION 1/37 (2.7%) 1/24 (4.2%) 0/10 (0%)
    HYPOKALAEMIA 0/37 (0%) 2/24 (8.3%) 0/10 (0%)
    HYPOVOLAEMIA 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    Musculoskeletal and connective tissue disorders
    BACK PAIN 0/37 (0%) 1/24 (4.2%) 1/10 (10%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ALVEOLAR SOFT PART SARCOMA METASTATIC 0/37 (0%) 0/24 (0%) 1/10 (10%)
    TUMOUR HAEMORRHAGE 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Nervous system disorders
    COGNITIVE DISORDER 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    SCIATICA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Psychiatric disorders
    DELIRIUM 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    DISORIENTATION 0/37 (0%) 1/24 (4.2%) 0/10 (0%)
    FEAR 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 2/37 (5.4%) 0/24 (0%) 0/10 (0%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    DYSPNOEA 2/37 (5.4%) 0/24 (0%) 0/10 (0%)
    PNEUMONITIS 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    Vascular disorders
    CAPILLARY LEAK SYNDROME 1/37 (2.7%) 0/24 (0%) 0/10 (0%)
    Other (Not Including Serious) Adverse Events
    Arm I Arm II Arm III
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 35/37 (94.6%) 21/24 (87.5%) 10/10 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 8/37 (21.6%) 9/24 (37.5%) 3/10 (30%)
    ANAEMIA OF MALIGNANT DISEASE 1/37 (2.7%) 2/24 (8.3%) 0/10 (0%)
    LEUKOPENIA 3/37 (8.1%) 1/24 (4.2%) 1/10 (10%)
    LYMPHOPENIA 1/37 (2.7%) 2/24 (8.3%) 0/10 (0%)
    THROMBOCYTOPENIA 5/37 (13.5%) 0/24 (0%) 0/10 (0%)
    Cardiac disorders
    BUNDLE BRANCH BLOCK RIGHT 0/37 (0%) 0/24 (0%) 1/10 (10%)
    CARDIOMEGALY 0/37 (0%) 0/24 (0%) 1/10 (10%)
    SINUS BRADYCARDIA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    TACHYCARDIA 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    Ear and labyrinth disorders
    VERTIGO 1/37 (2.7%) 0/24 (0%) 2/10 (20%)
    Endocrine disorders
    CUSHING'S SYNDROME 0/37 (0%) 0/24 (0%) 1/10 (10%)
    HYPERTHYROIDISM 1/37 (2.7%) 1/24 (4.2%) 1/10 (10%)
    TOXIC NODULAR GOITRE 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Eye disorders
    LACRIMATION INCREASED 0/37 (0%) 0/24 (0%) 1/10 (10%)
    MYOPIA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    VISION BLURRED 0/37 (0%) 0/24 (0%) 1/10 (10%)
    VISUAL IMPAIRMENT 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Gastrointestinal disorders
    ABDOMINAL PAIN 4/37 (10.8%) 7/24 (29.2%) 3/10 (30%)
    APHTHOUS ULCER 3/37 (8.1%) 0/24 (0%) 1/10 (10%)
    ASCITES 1/37 (2.7%) 4/24 (16.7%) 0/10 (0%)
    CONSTIPATION 1/37 (2.7%) 3/24 (12.5%) 2/10 (20%)
    DIARRHOEA 5/37 (13.5%) 6/24 (25%) 3/10 (30%)
    DRY MOUTH 1/37 (2.7%) 3/24 (12.5%) 1/10 (10%)
    DYSPEPSIA 0/37 (0%) 1/24 (4.2%) 1/10 (10%)
    DYSPHAGIA 2/37 (5.4%) 0/24 (0%) 1/10 (10%)
    FLATULENCE 1/37 (2.7%) 3/24 (12.5%) 0/10 (0%)
    GASTROINTESTINAL DISORDER 0/37 (0%) 0/24 (0%) 1/10 (10%)
    GINGIVAL BLEEDING 0/37 (0%) 0/24 (0%) 1/10 (10%)
    MOUTH ULCERATION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    NAUSEA 8/37 (21.6%) 8/24 (33.3%) 3/10 (30%)
    PROCTITIS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    STOMATITIS 10/37 (27%) 4/24 (16.7%) 5/10 (50%)
    TOOTHACHE 2/37 (5.4%) 0/24 (0%) 0/10 (0%)
    VOMITING 6/37 (16.2%) 5/24 (20.8%) 3/10 (30%)
    General disorders
    ASTHENIA 3/37 (8.1%) 1/24 (4.2%) 1/10 (10%)
    CHEST PAIN 0/37 (0%) 0/24 (0%) 2/10 (20%)
    CHILLS 1/37 (2.7%) 1/24 (4.2%) 1/10 (10%)
    DYSPLASIA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    FATIGUE 10/37 (27%) 9/24 (37.5%) 5/10 (50%)
    GENERAL PHYSICAL HEALTH DETERIORATION 3/37 (8.1%) 1/24 (4.2%) 0/10 (0%)
    GENERALISED OEDEMA 2/37 (5.4%) 0/24 (0%) 0/10 (0%)
    IMPAIRED HEALING 0/37 (0%) 0/24 (0%) 1/10 (10%)
    MEDICAL DEVICE PAIN 0/37 (0%) 0/24 (0%) 1/10 (10%)
    MUCOSAL INFLAMMATION 10/37 (27%) 4/24 (16.7%) 3/10 (30%)
    NON-CARDIAC CHEST PAIN 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    OEDEMA PERIPHERAL 6/37 (16.2%) 6/24 (25%) 3/10 (30%)
    PAIN 3/37 (8.1%) 0/24 (0%) 1/10 (10%)
    PERIPHERAL SWELLING 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    PYREXIA 10/37 (27%) 3/24 (12.5%) 3/10 (30%)
    Hepatobiliary disorders
    HEPATIC LESION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Immune system disorders
    CONTRAST MEDIA ALLERGY 0/37 (0%) 1/24 (4.2%) 2/10 (20%)
    Infections and infestations
    BRONCHITIS 4/37 (10.8%) 1/24 (4.2%) 0/10 (0%)
    CHRONIC SINUSITIS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    CYSTITIS 1/37 (2.7%) 1/24 (4.2%) 2/10 (20%)
    FEBRILE INFECTION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    GASTROENTERITIS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    GASTROENTERITIS VIRAL 0/37 (0%) 0/24 (0%) 1/10 (10%)
    INFLUENZA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    ORAL INFECTION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    PHARYNGITIS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    PNEUMONIA 1/37 (2.7%) 0/24 (0%) 2/10 (20%)
    RHINITIS 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    SINUSITIS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    URINARY TRACT INFECTION 3/37 (8.1%) 0/24 (0%) 1/10 (10%)
    VIRAL UPPER RESPIRATORY TRACT INFECTION 4/37 (10.8%) 1/24 (4.2%) 5/10 (50%)
    Injury, poisoning and procedural complications
    RADIATION SKIN INJURY 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 2/37 (5.4%) 0/24 (0%) 0/10 (0%)
    ASPARTATE AMINOTRANSFERASE INCREASED 4/37 (10.8%) 0/24 (0%) 1/10 (10%)
    BLOOD ALKALINE PHOSPHATASE INCREASED 3/37 (8.1%) 3/24 (12.5%) 0/10 (0%)
    BLOOD CHOLESTEROL INCREASED 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    BLOOD CREATININE INCREASED 3/37 (8.1%) 1/24 (4.2%) 0/10 (0%)
    BLOOD LACTATE DEHYDROGENASE INCREASED 4/37 (10.8%) 3/24 (12.5%) 0/10 (0%)
    C-REACTIVE PROTEIN INCREASED 4/37 (10.8%) 7/24 (29.2%) 1/10 (10%)
    CLOSTRIDIUM TEST POSITIVE 0/37 (0%) 0/24 (0%) 1/10 (10%)
    GAMMA-GLUTAMYLTRANSFERASE INCREASED 6/37 (16.2%) 3/24 (12.5%) 0/10 (0%)
    TRANSAMINASES INCREASED 5/37 (13.5%) 5/24 (20.8%) 2/10 (20%)
    WEIGHT DECREASED 7/37 (18.9%) 7/24 (29.2%) 1/10 (10%)
    Metabolism and nutrition disorders
    CACHEXIA 0/37 (0%) 2/24 (8.3%) 1/10 (10%)
    DECREASED APPETITE 13/37 (35.1%) 6/24 (25%) 1/10 (10%)
    HYPERGLYCAEMIA 2/37 (5.4%) 0/24 (0%) 0/10 (0%)
    HYPOCALCAEMIA 0/37 (0%) 2/24 (8.3%) 0/10 (0%)
    HYPOKALAEMIA 10/37 (27%) 5/24 (20.8%) 0/10 (0%)
    IRON DEFICIENCY 0/37 (0%) 0/24 (0%) 1/10 (10%)
    TYPE 1 DIABETES MELLITUS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    TYPE 2 DIABETES MELLITUS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 1/37 (2.7%) 1/24 (4.2%) 3/10 (30%)
    BACK PAIN 3/37 (8.1%) 0/24 (0%) 1/10 (10%)
    MUSCULOSKELETAL DISORDER 0/37 (0%) 0/24 (0%) 1/10 (10%)
    MUSCULOSKELETAL PAIN 2/37 (5.4%) 0/24 (0%) 3/10 (30%)
    MUSCULOSKELETAL STIFFNESS 0/37 (0%) 0/24 (0%) 1/10 (10%)
    PAIN IN EXTREMITY 1/37 (2.7%) 1/24 (4.2%) 2/10 (20%)
    PAIN IN JAW 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    METASTASES TO CENTRAL NERVOUS SYSTEM 0/37 (0%) 0/24 (0%) 1/10 (10%)
    TUMOUR PAIN 2/37 (5.4%) 0/24 (0%) 0/10 (0%)
    Nervous system disorders
    DYSAESTHESIA 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    DYSGEUSIA 3/37 (8.1%) 4/24 (16.7%) 1/10 (10%)
    HEADACHE 4/37 (10.8%) 2/24 (8.3%) 5/10 (50%)
    MIGRAINE 0/37 (0%) 1/24 (4.2%) 1/10 (10%)
    SEIZURE 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Psychiatric disorders
    DEPRESSION 1/37 (2.7%) 1/24 (4.2%) 1/10 (10%)
    INSOMNIA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    SLEEP DISORDER 2/37 (5.4%) 2/24 (8.3%) 1/10 (10%)
    Renal and urinary disorders
    CHRONIC KIDNEY DISEASE 1/37 (2.7%) 2/24 (8.3%) 0/10 (0%)
    DYSURIA 1/37 (2.7%) 1/24 (4.2%) 1/10 (10%)
    NOCTURIA 3/37 (8.1%) 3/24 (12.5%) 0/10 (0%)
    URINARY RETENTION 0/37 (0%) 2/24 (8.3%) 0/10 (0%)
    Reproductive system and breast disorders
    AMENORRHOEA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    MENORRHAGIA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    VAGINAL DISCHARGE 0/37 (0%) 0/24 (0%) 1/10 (10%)
    VULVOVAGINAL INFLAMMATION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 3/37 (8.1%) 3/24 (12.5%) 5/10 (50%)
    DRY THROAT 0/37 (0%) 0/24 (0%) 1/10 (10%)
    DYSPNOEA 8/37 (21.6%) 6/24 (25%) 2/10 (20%)
    EPISTAXIS 0/37 (0%) 4/24 (16.7%) 1/10 (10%)
    OROPHARYNGEAL PAIN 0/37 (0%) 0/24 (0%) 1/10 (10%)
    PLEURAL EFFUSION 1/37 (2.7%) 1/24 (4.2%) 1/10 (10%)
    PLEURISY 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    PNEUMONITIS 0/37 (0%) 0/24 (0%) 2/10 (20%)
    Skin and subcutaneous tissue disorders
    ACNE 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    DRY SKIN 2/37 (5.4%) 2/24 (8.3%) 1/10 (10%)
    ECZEMA 3/37 (8.1%) 0/24 (0%) 1/10 (10%)
    NAIL DISORDER 3/37 (8.1%) 0/24 (0%) 0/10 (0%)
    NIGHT SWEATS 1/37 (2.7%) 0/24 (0%) 1/10 (10%)
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME 2/37 (5.4%) 2/24 (8.3%) 0/10 (0%)
    PHOTOSENSITIVITY REACTION 0/37 (0%) 0/24 (0%) 1/10 (10%)
    PRURITUS 2/37 (5.4%) 1/24 (4.2%) 1/10 (10%)
    RASH 8/37 (21.6%) 5/24 (20.8%) 3/10 (30%)
    TELANGIECTASIA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    Vascular disorders
    AORTIC ANEURYSM 0/37 (0%) 0/24 (0%) 1/10 (10%)
    HAEMATOMA 0/37 (0%) 0/24 (0%) 1/10 (10%)
    LYMPHOEDEMA 0/37 (0%) 0/24 (0%) 1/10 (10%)

    Limitations/Caveats

    [Not Specified]

    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.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email Novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00767819
    Other Study ID Numbers:
    • CRAD001C24114
    • 2007-005294-60
    First Posted:
    Oct 7, 2008
    Last Update Posted:
    Apr 1, 2019
    Last Verified:
    Dec 1, 2018