| ID | Type | Description | Link |
|---|---|---|---|
| CSTI571H2202 | Other Identifier | Novartis Pharmaceuticals |
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Lack of efficacy
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This was an investigational study to assess the objective overall response (OOR) rate (complete response [CR] + partial response [PR]) of imatinib mesylate and hydroxyurea (hydroxycarbamide) combination therapy in patients with recurrent glioblastoma multiforme (brain tumors). This study also evaluated the duration of tumor response (as per MacDonald criteria), clinical benefit, progression-free survival rate at 6 and 12 months, and the survival rate at 12 and 24 months.
This ClinicalTrials.gov record includes the results from two studies (Novartis protocol IDs CSTI571H2201 and CSTI571H2202) which were conducted separately but reported together in a single clinical study report. Both studies were phase II, open-label, multicenter, single-arm studies that evaluated the efficacy of imatinib mesylate plus hydroxyurea in subjects with progressive glioblastoma multiforme. The studies were identical in design with two exceptions: Patients in study CSTI571H2201 received a dose of imatinib 600 mg once daily and were not allowed concomitant use of enzyme-inducing anticonvulsant drugs (EIACDs); patients in study CSTI571H2202 received a dose of imatinib 500 mg twice daily and were allowed concomitant use of EIACDs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Imatinib 600 mg + hydroxyurea 1000 mg | Experimental | Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
|
| Imatinib 1000 mg + hydroxyurea 1000 mg | Experimental | Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imatinib tablets | Drug | Imatinib was supplied as 100 and 400 mg tablets by Novartis. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients With an Objective Overall Response (OOR) | Patients with an OOR were those whose best response to treatment was a complete response (CR) or a partial response (PR) assessed with magnetic resonance imaging. A patient had a CR if the target tumors disappeared. A patient had a PR if there was a ≥ 50% reduction in the sum of the products of the largest perpendicular diameters of the target tumors compared to the baseline value. A best response of CR required at least 2 determinations of CR at least 4 weeks apart. A best response of PR required at least 2 determinations of PR or better at least 4 weeks apart (and not qualifying for CR). | Baseline to end of study (Month 24) |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Objective Overall Response (OOR) | Duration of OOR only included patients whose best overall response was complete response (CR) or partial response (PR). The start date was the date of the first documented response (CR or PR); the end date was the date of the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, the duration of OOR was censored at the time of the last OOR assessment. |
Not provided
Inclusion criteria:
Exclusion Criteria:
Receipt of imatinib or hydroxyurea (HU) prior to study entry or receipt of any investigational agent within the last 6 months.
Patients who had received a second course of chemotherapy or radiotherapy, unless given as a single localized application of radio surgery.
In study STI571H2201 only, receipt of enzyme-inducing anticonvulsant drugs (EIACDs), eg, carbamazepine, phenobarbital, phenytoin, fosphenytoin, oxcarbazepine, or primidone. Previous EIACD should have been interrupted 4 weeks prior to study start.
Grade ≥ 2 peripheral edema or pulmonary or pericardial effusions or ascites of any grade.
Presence of any uncontrolled systemic infection.
Patients who were not a minimum of 12 weeks from completion of conventional external beam radiotherapy unless:
Evidence of intra-tumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative Grade 1 hemorrhage, patients with an excessive risk of an intracranial hemorrhagic event, and patients with history of central nervous system (excluding post-operative Grade 1) or intraocular bleed.
Patients who had undergone major surgery within 2 weeks prior to study entry or who had not recovered from prior major surgery, patients who had received chemotherapy within 4 weeks prior to study start, or who have not recovered from toxic effects of such therapy.
Impairment of gastrointestinal function or gastrointestinal disease that could significantly alter the absorption of imatinib.
Patients taking warfarin sodium.
Known history of human immunodeficiency virus (HIV) seropositivity; testing for HIV was not required at study entry.
For the purposes of MRI, patients with a pacemaker, ferromagnetic metal implants other than those approved as safe for use in MR scanners (eg, some types of aneurysm clips, shrapnel), patients suffering from uncontrollable claustrophobia, or those physically unable to fit into the machine (eg, obesity).
Patients considered by the investigator as unlikely to be compliant with the study, take the study medications, travel for the necessary assessment visits, or have other medical conditions likely to interfere with the study assessments.
Patients with another primary malignancy treated within the prior 3 years except excised squamous cell carcinomas of the skin and carcinoma in situ lesions of other organs which had been treated for cure.
Patients not able to provide reliable informed consent and who did not have a legal representative for healthcare decisions on their behalf.
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| Name | Affiliation | Role |
|---|---|---|
| David Reardon, Dr. | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Imatinib 600 mg + Hydroxyurea 1000 mg | Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
| FG001 | Imatinib 1000 mg + Hydroxyurea 1000 mg | Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Imatinib 600 mg + Hydroxyurea 1000 mg | Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Patients With an Objective Overall Response (OOR) | Patients with an OOR were those whose best response to treatment was a complete response (CR) or a partial response (PR) assessed with magnetic resonance imaging. A patient had a CR if the target tumors disappeared. A patient had a PR if there was a ≥ 50% reduction in the sum of the products of the largest perpendicular diameters of the target tumors compared to the baseline value. A best response of CR required at least 2 determinations of CR at least 4 weeks apart. A best response of PR required at least 2 determinations of PR or better at least 4 weeks apart (and not qualifying for CR). | Intent-to-treat (ITT) population: All patients who received at least 1 dose of any of the 2 study drugs. | Posted | Number | 95% Confidence Interval | Percentage of participants | Baseline to end of study (Month 24) |
|
Not provided
The analysis was done on the safety population which consisted of 131 patients in the imatinib 600 mg plus hydroxyurea 1000 mg group and 99 patients in the imatinib 1000 mg plus hydroxyurea 1000 mg group.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Imatinib 600 mg + Hydroxyurea 1000 mg | Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862 778-8300 |
Not provided
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D005910 | Glioma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
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| ID | Term |
|---|---|
| D000068877 | Imatinib Mesylate |
| D006918 | Hydroxyurea |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 |
Not provided
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|
| Hydroxyurea capsules | Drug | Hydroxyurea was supplied locally as 500 mg capsules. |
|
| Baseline to end of study (Month 24) |
| Percentage of Patients Who Had Clinical Benefit | Patients who had clinical benefit were patients with a best response of complete response (CR), partial response (PR), or stable disease (SD) lasting for more than 6 months from the start of treatment until the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. SD was defined as insufficient tumor shrinkage to qualify for PR or CR and no increase in lesions which would qualify as PD. | Baseline to end of study (Month 24) |
| Percentage of Patients With Progression-free Survival at Months 6 and 12 | Progression-free survival (PFS) was defined as the time from the start of treatment to the date of the first documented disease progression (PD) or death due to any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, progression-free survival was censored at the time of the last overall response assessment. | Months 6 and 12 |
| Percentage of Patients Surviving at Months 6, 12, and 24 | Patients not known to have died were censored at the time of last survival follow-up. | Months 6, 12, and 24 |
| Number of Patients With at Least 1 Adverse Event | An adverse event (AE) is any undesirable sign, symptom, or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. Study drug refers to imatinib or hydroxyurea. The study treatment is the combination of these two study drugs. | Baseline to end of study (Month 24) |
| Adverse Event |
|
| Withdrawal by Subject |
|
| Administrative problems |
|
| Protocol Violation |
|
| Lost to Follow-up |
|
| BG001 | Imatinib 1000 mg + Hydroxyurea 1000 mg | Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs.
| OG001 | Imatinib 1000 mg + Hydroxyurea 1000 mg | Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs. |
| OG002 | All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg | Patients took either imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal or imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. |
|
|
| Secondary | Duration of Objective Overall Response (OOR) | Duration of OOR only included patients whose best overall response was complete response (CR) or partial response (PR). The start date was the date of the first documented response (CR or PR); the end date was the date of the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, the duration of OOR was censored at the time of the last OOR assessment. | Intent-to-treat (ITT) population: All patients who received at least 1 dose of any of the 2 study drugs. | Posted | Median | 95% Confidence Interval | Weeks | Baseline to end of study (Month 24) |
|
|
|
| Secondary | Percentage of Patients Who Had Clinical Benefit | Patients who had clinical benefit were patients with a best response of complete response (CR), partial response (PR), or stable disease (SD) lasting for more than 6 months from the start of treatment until the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. SD was defined as insufficient tumor shrinkage to qualify for PR or CR and no increase in lesions which would qualify as PD. | Intent-to-treat (ITT) population: All patients who received at least 1 dose of any of the 2 study drugs. | Posted | Number | 95% Confidence Interval | Percentage of participants | Baseline to end of study (Month 24) |
|
|
|
| Secondary | Percentage of Patients With Progression-free Survival at Months 6 and 12 | Progression-free survival (PFS) was defined as the time from the start of treatment to the date of the first documented disease progression (PD) or death due to any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, progression-free survival was censored at the time of the last overall response assessment. | Intent-to-treat (ITT) population: All patients who received at least 1 dose of any of the 2 study drugs. | Posted | Number | 95% Confidence Interval | Percentage of participants | Months 6 and 12 |
|
|
|
| Secondary | Percentage of Patients Surviving at Months 6, 12, and 24 | Patients not known to have died were censored at the time of last survival follow-up. | Intent-to-treat (ITT) population: All patients who received at least 1 dose of any of the 2 study drugs. | Posted | Number | 95% Confidence Interval | Percentage of participants | Months 6, 12, and 24 |
|
|
|
| Secondary | Number of Patients With at Least 1 Adverse Event | An adverse event (AE) is any undesirable sign, symptom, or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. Study drug refers to imatinib or hydroxyurea. The study treatment is the combination of these two study drugs. | Safety population: All patients who received at least 1 dose of either of the 2 study drugs and who had at least 1 post-baseline safety assessment. | Posted | Number | Participants | Baseline to end of study (Month 24) |
|
|
|
| 62 |
| 131 |
| 122 |
| 131 |
| EG001 | Imatinib 1000 mg + Hydroxyurea 1000 mg | Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs. | 53 | 99 | 95 | 99 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Amaurosis | Eye disorders | MedDRA | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA | Systematic Assessment |
|
| Abdominal mass | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Palatal oedema | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Peritonitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Retroperitoneal haematoma | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Retroperitoneal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Sigmoiditis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA | Systematic Assessment |
|
| Oedema | General disorders | MedDRA | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Sudden death | General disorders | MedDRA | Systematic Assessment |
|
| Hepatotoxicity | Hepatobiliary disorders | MedDRA | Systematic Assessment |
|
| Alpha haemolytic streptococcal infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Beta haemolytic streptococcal infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pneumocystis jiroveci pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pneumonia staphylococcal | Infections and infestations | MedDRA | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Septic embolus | Infections and infestations | MedDRA | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA | Systematic Assessment |
|
| Staphylococcal sepsis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Wound infection staphylococcal | Infections and infestations | MedDRA | Systematic Assessment |
|
| Brain herniation | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Therapeutic agent toxicity | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Blood amylase increased | Investigations | MedDRA | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Intracranial tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
|
| Metastases to meninges | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
|
| Renal neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Cerebral cyst | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Grand mal convulsion | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hemiplegia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hypokinesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hypotonia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Intracranial pressure increased | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Neurological decompensation | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Partial seizures | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Tongue biting | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Personality change due to a general medical condition | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Staring | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Stress | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Incontinence | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Bronchopneumopathy | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Respiratory arrest | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Cushingoid | Endocrine disorders | MedDRA | Systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA | Systematic Assessment |
|
| Oedema | General disorders | MedDRA | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
|
| Pain | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Amnesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Speech disorder | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Incontinence | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Sexual dysfunction | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
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.
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D014508 | Urea |
|
|
| 24 Months |
|