Symptoms and General Pathology

All Conditions

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Rare Diseases

Recurrence

Glioma

Glioblastoma

Disease Attributes

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

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All Drugs and Chemicals

Anticonvulsants

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Amino Acids

Hydroxyurea

Imatinib Mesylate

Lactitol

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

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.

Imatinib was supplied as 100 and 400 mg tablets by Novartis.

Imatinib tablets

Hydroxyurea was supplied locally as 500 mg capsules.

Hydroxyurea capsules

David Reardon, Dr.

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.

Efficacy and Safety of Imatinib Mesylate Plus Hydroxyurea (HU) in Patients With Recurrent Glioblastoma Multiforme (GBM)

A Phase II, Open-label, Multicenter Study Evaluating the Efficacy of Imatinib Plus Hydroxyurea (HU) in Patients With Progressive Glioblastoma Multiforme (GBM) Receiving or Not Receiving Enzyme-inducing Anticonvulsant Drugs (EIACDs)

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).

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.

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.

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.

Patients not known to have died were censored at the time of last survival follow-up.

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.

Novartis

External Affairs

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.

Imatinib 600 mg + Hydroxyurea 1000 mg

Imatinib 1000 mg + Hydroxyurea 1000 mg

Total

Age Continuous

Sex: Female, Male

Study Director

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.

All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg

Intent-to-treat (ITT) population: All patients who received at least 1 dose of any of the 2 study drugs.

Percentage of Patients With an Objective Overall Response (OOR)

Duration of Objective Overall Response (OOR)

Percentage of Patients Who Had Clinical Benefit

6 Months

12 Months

Percentage of Patients With Progression-free Survival at Months 6 and 12

24 Months

Percentage of Patients Surviving at Months 6, 12, and 24

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.

Number of Patients With at Least 1 Adverse Event

Overall Study

Skin and Connective Tissue Diseases

Melanoma

Skin Neoplasms

Neuroendocrine Tumors

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Imatinib mesylate (STI571)

Kevin Kim, MD

Menashe Bar-Eli, PhD

RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and may be an effective treatment for metastatic melanoma.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have metastatic melanoma.

OBJECTIVES:

* Determine the clinical activity of imatinib mesylate (STI571) in patients with metastatic melanoma.
* Determine the side effects of this drug in these patients.
* Correlate molecular studies with responsiveness to this drug in these patients.

OUTLINE: Patients receive oral imatinib mesylate (STI571) twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21-78 patients will be accrued for this study within 6-15 months.

Imatinib Mesylate in Treating Patients With Metastatic Melanoma

Phase II Trial of Gleevec (Imatinib Mesylate, STI-571) in Metastatic Melanoma

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Nervous System Diseases

Adenocarcinoma

Brain Neoplasms

Temozolomide

Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening.

1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea.

Imatinib was supplied as 100 mg and 400 mg tablets packaged in polyethylene bottles.

Imatinib mesylate

Novartis Pharmaceuticals

This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy with hydroxyurea monotherapy in patients with temozolomide resistant progressive glioblastoma.

Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma

Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma

PFS was defined as the time from the date of randomization to the date of the first documented progression according to the MacDonald criteria, or death due to any cause. MacDonald criteria are standard criteria in neurooncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).

National Cancer Institute (NCI)/ National Institute of Health (NIH) provides a grading (severity) scale for each AE term. Grade 3 refers to severe AE and Grade 4 refers to life-threatening or disabling AE. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.

Safety population = patients who were randomized to either Imatinib + Hydroxyurea (combination)\[n=118\] or to Hydroxyurea alone \[n=118\]. Every 6 wks, patients on Hydroxyurea alone switched to combination arm depending on response. So, for the safety analysis Hydroxyurea arm is divided into Hydroxyurea alone \[n=118\] or switch to combination \[n=85\].

Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Patients receiving a daily dose of 800 mg imatinib with 1000 mg HU were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening.

Imatinib Mesylate + Hydroxyurea (HU)

1500 mg/day of HU given as 500 mg 3 times daily.

Period With Hydroxyurea Alone

After every 6 weeks from randomization, depending on the assessment of therapeutic effect, patients were switched from Hydroxyurea (1500 mg/day p.o) to combination arm where patients were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time).

Period After Switch to Combination

Hydroxyurea Alone

6 months

12 months

The ITT population consists of all randomized patients, analyzed according to their randomized treatment.

Percentage of Participants With Progression Free Survival (PFS) During the Study Duration

Deaths

Death due to disease progression

Serious Adverse Events (SAEs)

NCI/NIH Grade 3 (severe) or 4 (life threatening)

Suspected to be drug-related

Leading to dose adjustment or interruption

Leading to permanent discontinuation

The safety population consisted of randomized patients with at least one dose of randomized medication.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Imatinib Mesylate Plus Hydroxyurea (HU) in Patients With Recurrent Glioblastoma Multiforme (GBM)	NCT00290771	Recurrent Gliob...	Imatinib tablet... Hydroxyurea cap...	18 Years -	Novartis
Imatinib Mesylate in Treating Patients With Metastatic Melanoma	NCT00027586	Melanoma Skin Neoplasms	Imatinib mesyla...	-	M.D. Anderson Cancer Center
Imatinib Mesylate in Treating Patients With Metastatic Melanoma	NCT00027586	Melanoma Skin Neoplasms	Imatinib mesyla...	-	M.D. Anderson Cancer Center
Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma	NCT00154375	Glioblastoma Mu... Astrocytoma	Imatinib mesyla... Hydroxyurea	18 Years - 70 Years	Novartis
Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma	NCT00154375	Glioblastoma Mu... Astrocytoma	Imatinib mesyla... Hydroxyurea	18 Years - 70 Years	Novartis

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