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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00681 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000495253 | |||
| NABTT 0504 | Other Identifier | Adult Brain Tumor Consortium | |
| NABTT-0504 | Other Identifier | CTEP | |
| U01CA137443 | U.S. NIH Grant/Contract | View source |
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This phase I/II trial is studying the side effects and best dose of tandutinib and to see how well it works in treating patients with recurrent or progressive glioblastoma.Tandutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PRIMARY OBJECTIVES:
I. Assess the ability of tandutinib to achieve a target tumor/plasma ratio ≥ 0.33 in patients with recurrent glioblastoma undergoing resection. (Feasibility study) II. Detect potential biological effects of tandutinib by measuring platelet-derived growth factor receptor phosphorylation status and downstream activation of Akt and Erk. (Feasibility study) III. Determine the maximum tolerated dose of tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) IV. Estimate the frequency of toxicities associated with tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) V. Describe the pharmacokinetics of this route of administration in patients with recurrent or progressive glioblastoma. (Phase I) VI. Assess tumor response rate in patients with recurrent or progressive glioblastoma. (Phase II)
SECONDARY OBJECTIVES:
I. Estimate overall survival of patients with recurrent or progressive glioblastoma. (Phase II) II. Estimate the 6-month progression-free survival rate in these patients. (Phase II) III. Assess the toxicities associated with tandutinib in these patients. (Phase II) IV. Assess the pharmacokinetic profile of this route of administration in these patients. (Phase II) V. Explore protein-expression patterns that distinguish patients who respond to therapy from those who do not. (Phase II)
OUTLINE: This is a multicenter, prospective, nonrandomized, feasibility study and phase I study (in parallel) followed by an open label phase II study.
FEASIBILITY STUDY: Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PHASE I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
[Note: *On day 1 of course 1, patients receive only 1 dose of tandutinib.]
PHASE II: Patients receive tandutinib as in phase I at the MTD determined in phase I.
Patients undergo blood sample collection for pharmacokinetic studies. Patients in the feasibility portion of the study also undergo blood and tissue sample collection for correlative studies by mass spectrometry for tandutinib concentration. Samples are also examined for circulating endothelial cells and plasma proteins (vascular endothelial growth factor [VEGF]-A, -B, -C, and -D, soluble VEGF receptors [sVEGFR's], placental growth factor [P1GF], platelet-derived growth factor [PDGF]-AA, PDGF-AB, PDGF-BB, angiopoietin-1 and -2, tumstatin, thrombospondin-1, and IL-8) as potential markers of the antiangiogenic effect of tandutinib.
After completion of study treatment, patients are followed every 2 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I - Feasibility | Experimental | Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. conventional surgery oral tandutinib Pharmacological study Tissue samples |
|
| Arm 2 - Dose Escalation (Phase 1) | Experimental | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. the starting dose for tandtinib is 500mg BID oral tandutinib Pharmacological study Tissue samples |
|
| Arm 3 - Phase 2 | Experimental | Patients receive tandutinib as in phase I at the MTD determined in phase I. 600mg was the determined MTD in Dose Escalation oral tandutinib Pharmacological study Tissue samples |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| conventional surgery | Procedure | Undergo surgery |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose of Tandutinib Defined by Dose Limiting Toxicities (Phase 1) | cycle 1 - 28 days | |
| To Determine the Tumor/Plasma Ratio of in Subjects With Recurrent GBM Undergoing Resections (Phase 0) | participants are administered tandutinib (500mg BID) for 7 days prior to surgery and then undergo resection for recurrent glioblastoma. Tissue samples will be collected for correlative studies - determine tumor/plasma ratio. | 7 days prior to surgery including surgery |
| Number of Dose Limiting Toxicities Per Dose Level | cohorts of 3-6 pts will recieve oral tandutinib starting at 500mg BID with a dose escalation in each cohort. Each treatment cycle is 28 days. Evaluation period for MTD is 1st cycle - 28 days. dose limiting toxicity defined as: grades 3-4 severity (except vomiting and diarrhea without sufficient prophylaxis delay of treatment > 14 days. ANC less/equal 500m/mm3; Plts less/equal 25,000/mm3; febrile neutropenia or delay of treatment > 14 days | 28 days |
| Tumor Response (Complete Response and Partial Response) Rate (Phase II) | pts receive a scan baseline and prior to every odd cycle. All responses are centrally reviewed Complete response Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks. Progressive disease Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. Stable disease Clinical status and MRI does not qualify for complete response, partial response or progression | Up to 4 years |
| Pharmacokinetics (Max Concentration of Plasma) for Tandutinib in Phase 1 and Phase 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (Phase II) | Median time of survival along with 95% confidence interval will be estimated using Kaplan-Meier method. An overall failure rate will be estimated with 95% CI. | Up to 4 years |
| Six-month Progression-free Survival Rate (Phase II) |
Not provided
Criteria:
Histologically confirmed glioblastoma:
Measurable disease, defined as contrast-enhancing progressive or recurrent glioblastoma by MRI or CT imaging within the past 2 weeks
Must be maintained on a stable corticosteroid regimen from the time of baseline scan to the start of study treatment
Feasibility study only:
Karnofsky performance status 60-100%
Absolute neutrophil count >= 1,500/mm^3
Hemoglobin >= 10 mg/dL
Bilirubin =< 1.5 mg/dL
AST and ALT =< 4 times upper limit of normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment
Mini Mental State Exam score >= 15
Mean QTc =< 500 msec (with Bazett's correction) by screening electrocardiogram
LVEF >= 40%
No history of familial long QT syndrome
No myocardial infarction within the past 6 months
No severe uncontrolled ventricular arrhythmias
No uncontrolled angina
No electrocardiographic evidence of acute ischemia or active conduction system abnormalities
No ongoing vomiting or nausea >= grade 2
No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous alimentation
No active peptic ulcer disease
No other condition that would impair ability to swallow pills or absorb oral medications
No muscular dystrophy
No myasthenia gravis
No other known or suspected primary muscular or neuromuscular disease
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tandutinib (e.g., erlotinib hydrochloride, gefetinib, or doxazosin mesylate)
Patients who developed an acneiform/maculopustular rash while receiving either gefitinib or erlotinib hydrochloride are eligible unless the rash is considered an allergic reaction (angioedema/urticaria) or Stevens-Johnson syndrome
No ongoing or active infections
No psychiatric illness or social situations that would preclude study compliance
No other serious infection or medical illness
At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
No other uncontrolled illness
No other malignancy within the past 5 years except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
Recovered from prior therapy
At least 3 months since prior radiotherapy
No prior surgical procedures affecting absorption
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational agents
No concurrent agent that would cause QTc prolongation
No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
At least 10 days since prior and no concurrent anticonvulsant drugs that induce hepatic metabolic enzymes (e.g., primidone, oxcarbazepine, phenytoin, carbamazepine, or phenobarbital)
No prior treatment with small molecule inhibitors of platelet-derived growth factor receptor (e.g., sunitinib malate, sorafenib, or imatinib mesylate)
Platelet count >= 100,000/mm^3
No New York Heart Association class III or IV heart failure
Creatinine =< 1.5 mg/dL OR creatinine clearance >= 60mL/min
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| Name | Affiliation | Role |
|---|---|---|
| Tracy Batchelor, MD | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| H. Lee Moffitt Cancer Center and Research Institute |
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Patients enrolled from 4/2007 through 6/2010. Patients accrued in the outpatient clinical setting. The first part of study was for patients who required surgery. Hence these patients were treated in-patient.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1- Phase 0 | Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. conventional surgery oral tandutinib Pharmacological study Tissue samples |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| tandutinib | Drug | Given orally |
|
|
| pharmacological study | Other | Correlative studies |
|
| Tissue samples | Other | Correlative studies |
|
pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2
| 28 days |
| Pharmacokinetics (Apparent Terminal Phase Half-life) for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 28 days |
| Pharmacokinetics (Area Under the Plasma Concentration Time Profile From Zero to Infinity (AUC)) for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 28 days |
| Pharmacokinetics; Apparent Oral Clearance for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 28 days |
| Pharmacokinetics; Apparent Oral Total Body Volume of Distribution for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 28 days |
| Pharmacokinetics; Steady-state Trough Concentration for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 28 days |
The probability of 6-momth progression-free survival will be estimated using binomial distribution. Progression defined as: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. |
| At 6 months |
| Overall Failure Rate (Phase II) | The overall failure rate is expressed as hazard of failure per person-year of follow-up. | up to 4 years |
| Proportion of Patients With Serious or Life Threatening Toxicities | Grade 3 or 4 toxicities related to treatment as determined by the CTCAE | 2 year period |
| Protein Expression Patterns Post Treatment - Loss or Gain | serial blood samples over multiple time points (prior to treatment, 2 days post treatment, 8 days post treatment, 10 days post treatment and 28 days post treatment. statistical analyses presented for the comparisons that yielded a p-value <=0.05 | baseline - cycle 2 (28 days) |
| Tampa |
| Florida |
| 33612 |
| United States |
| Emory University | Atlanta | Georgia | 30322 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| Massachusetts General Hospital Cancer Center | Boston | Massachusetts | 02114 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| FG001 | Arm 2 - Phase 1 | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. tandutinib: Given orally pharmacological study: Correlative studies |
| FG002 | Arm 3 - Phase 2 | Patients receive tandutinib as in phase I at the MTD determined in phase I. 600mg was the determined MTD in Dose Escalation oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
| COMPLETED |
|
| NOT COMPLETED |
|
|
all pts had to have confirmed histological GBM, prior treatment wih RT and a MMSE of greater or equal to 15.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 - Phase 0 | Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. conventional surgery oral tandutinib Pharmacological study Tissue samples |
| BG001 | Arm 2 - Phase 1 | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. tandutinib: Given orally pharmacological study: Correlative studies |
| BG002 | Arm 3 - Phase 2 | Patients receive tandutinib as in phase I at the MTD determined in phase I. 600mg was the determined MTD in Dose Escalation oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Karnofsky Performance Status | Higher score better 100 normal no complaints/disease 90 capable normal activity few symptoms/disease 80 normal activity, some difficulty some symptoms/signs 70 caring for self not capable normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death | Median | Full Range | Percentage |
| ||||||||||||||
| Mini Mental Score | The mini-mental state examination (MMSE) is a 30-point questionnaire test used to screen for cognitive impairment. Commonly used to screen for dementia. It is also used to estimate the severity of cognitive impairment and to follow the course of cognitive changes in an individual over time. The MMSE test includes simple questions and problems in a number of areas: the time and place of the test, repeating lists of words, arithmetic such as the serial sevens, language use and comprehension, and basic motor skills. The Higher your score, the higher your function. Scale Ranges from 1-30 | Median | Full Range | units on a scale |
| ||||||||||||||
| Steroids | Number | participants |
|
| 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 | Maximum Tolerated Dose of Tandutinib Defined by Dose Limiting Toxicities (Phase 1) | 19 patients enrolled in dose escalation but 4 were removed for reasons other than drug related toxicity | Posted | Number | mg BID | cycle 1 - 28 days |
|
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| Primary | To Determine the Tumor/Plasma Ratio of in Subjects With Recurrent GBM Undergoing Resections (Phase 0) | participants are administered tandutinib (500mg BID) for 7 days prior to surgery and then undergo resection for recurrent glioblastoma. Tissue samples will be collected for correlative studies - determine tumor/plasma ratio. | a tandutinib tumor:plasma ratio of >/=0.33 was the objective in a minimum of 3/6 subjects in order to proceed with Phase 1/2 study. 6 samples received, but 2 samples were found to be thawed at receipt and not used in analysis | Posted | Mean | Standard Deviation | ratio | 7 days prior to surgery including surgery |
|
| ||||||||||||||||||||||||||
| Primary | Number of Dose Limiting Toxicities Per Dose Level | cohorts of 3-6 pts will recieve oral tandutinib starting at 500mg BID with a dose escalation in each cohort. Each treatment cycle is 28 days. Evaluation period for MTD is 1st cycle - 28 days. dose limiting toxicity defined as: grades 3-4 severity (except vomiting and diarrhea without sufficient prophylaxis delay of treatment > 14 days. ANC less/equal 500m/mm3; Plts less/equal 25,000/mm3; febrile neutropenia or delay of treatment > 14 days | all GBM, All prior treatment with RT. assessment was for 28 days, cycle 1. 3 dose levels 500, 600 and 700mg | Posted | Number | participants | 28 days |
| ||||||||||||||||||||||||||||
| Primary | Tumor Response (Complete Response and Partial Response) Rate (Phase II) | pts receive a scan baseline and prior to every odd cycle. All responses are centrally reviewed Complete response Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks. Progressive disease Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. Stable disease Clinical status and MRI does not qualify for complete response, partial response or progression | In the first stage, 31 patients would be enrolled and the trial would be terminated if 3 or fewer patients demonstrated objective responses (partial response or complete response) | Posted | Number | participants with objective response | Up to 4 years |
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| Primary | Pharmacokinetics (Max Concentration of Plasma) for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 56 enrolled pts, 40 evaluable PK sample sets, parameters not estimated for 16 pts. (Sample collected after next dose taken 3pts;1st dose given before collecting redose sample 1 pt; concentration sample 24h after dosing \ | Posted | Median | Standard Deviation | ng/mL | 28 days |
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| Primary | Pharmacokinetics (Apparent Terminal Phase Half-life) for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 56 enrolled pts, 40 evaluable PK sample sets, parameters not estimated for 16 pts. (Sample collected after next dose taken 3pts;1st dose given before collecting redose sample 1 pt; concentration sample 24h after dosing \ | Posted | Median | Standard Deviation | h | 28 days |
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| Primary | Pharmacokinetics (Area Under the Plasma Concentration Time Profile From Zero to Infinity (AUC)) for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 56 enrolled pts, 40 evaluable PK sample sets, parameters not estimated for 16 pts. (Sample collected after next dose taken 3pts;1st dose given before collecting redose sample 1 pt; concentration sample 24h after dosing \ | Posted | Median | Standard Deviation | ng*h/mL | 28 days |
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| Primary | Pharmacokinetics; Apparent Oral Clearance for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 56 enrolled pts, 40 evaluable PK sample sets, parameters not estimated for 16 pts. (Sample collected after next dose taken 3pts;1st dose given before collecting redose sample 1 pt; concentration sample 24h after dosing \ | Posted | Median | Standard Deviation | L/h | 28 days |
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| Primary | Pharmacokinetics; Apparent Oral Total Body Volume of Distribution for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 56 enrolled pts, 40 evaluable PK sample sets, parameters not estimated for 16 pts. (Sample collected after next dose taken 3pts;1st dose given before collecting redose sample 1 pt; concentration sample 24h after dosing \ | Posted | Median | Standard Deviation | L | 28 days |
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| Primary | Pharmacokinetics; Steady-state Trough Concentration for Tandutinib in Phase 1 and Phase 2 | pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2 | 56 enrolled pts, 40 evaluable PK sample sets, parameters not estimated for 16 pts. (Sample collected after next dose taken 3pts;1st dose given before collecting redose sample 1 pt; concentration sample 24h after dosing \ | Posted | Median | Standard Deviation | ng/mL | 28 days |
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| Secondary | Overall Survival (Phase II) | Median time of survival along with 95% confidence interval will be estimated using Kaplan-Meier method. An overall failure rate will be estimated with 95% CI. | Median time of survival along with 95% confidence interval will be estimated using Kaplan-Meier method. An overall failure rate will be estimated with 95% CI. The overall failure rate is expressed as hazard of failure per person-year of follow-up. | Posted | Median | 95% Confidence Interval | months | Up to 4 years |
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| Secondary | Six-month Progression-free Survival Rate (Phase II) | The probability of 6-momth progression-free survival will be estimated using binomial distribution. Progression defined as: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. | The probability of 6-momth progression-free survival will be estimated using binomial distribution. | Posted | Number | 95% Confidence Interval | percent probability | At 6 months |
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| Secondary | Overall Failure Rate (Phase II) | The overall failure rate is expressed as hazard of failure per person-year of follow-up. | Posted | Number | 95% Confidence Interval | failure per person-year | up to 4 years |
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| Secondary | Proportion of Patients With Serious or Life Threatening Toxicities | Grade 3 or 4 toxicities related to treatment as determined by the CTCAE | Posted | Number | percentage of participants | 2 year period |
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| Secondary | Protein Expression Patterns Post Treatment - Loss or Gain | serial blood samples over multiple time points (prior to treatment, 2 days post treatment, 8 days post treatment, 10 days post treatment and 28 days post treatment. statistical analyses presented for the comparisons that yielded a p-value <=0.05 | peripheral blood was obtained from 20 patients enrolled in the phase 2 portion of the study. | Posted | Number | 95% Confidence Interval | hazard ratio | baseline - cycle 2 (28 days) |
|
Time of first dose until patient went off treatment. <4 years
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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 | Arm I - Feasibility | Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. conventional surgery oral tandutinib Pharmacological study Tissue samples conventional surgery: Undergo surgery tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies | 2 | 6 | 3 | 6 | ||
| EG001 | Arm 2 - Dose Escalation (Phase 1) | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. the starting dose for tandtinib is 500mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies | 3 | 15 | 15 | 15 | ||
| EG002 | Arm 3 - Phase 2 | Patients receive tandutinib as in phase I at the MTD determined in phase I. 600mg was the determined MTD in Dose Escalation oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies | 15 | 31 | 28 | 31 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| confusion | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| hypertension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| somnolence | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| intracranial hemorrhage | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| alanine aminotransferase increased | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| electrocardiogram QT corrected interval prolonged | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| lung infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
| |
| peripheral motor neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| fatigue | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Platelet count decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| electrocardiogram QT corrected interval prolonged | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| edema face | General disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| edema limb | General disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| white blood cell decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| creatinine increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| somnolence | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| rash maculopapular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| blood bilirubin increase | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| neutrophil count decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| alkaline phosphatase increase | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| blurred vision | Ear and labyrinth disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| confusion | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| dizziness | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| insomnia | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
Simon's two-stage design Phase 2, prespecified goal patients alive & progression-free survival 6-months not achieved first stage, 2nd stage not done & trial closed/stopped.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stuart A Grossman, MD Director of ABTC | Adult Brain Tumor Consortium | 410-955-8837 | grossman@jhmi.edu |
| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| C464670 | tandutinib |
Not provided
Not provided
Not provided
| Male |
|
| No |
|
|
|
| OG002 | Level 3 - 700mg BID | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. dose for tandtinib is 700mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
|
|
|
|
| OG002 | Level 3 - 700mg BID | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. dose for tandtinib is 700mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
|
|
| OG002 | Level 3 - 700mg BID | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. dose for tandtinib is 700mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
|
|
| OG002 | Level 3 - 700mg BID | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. dose for tandtinib is 700mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
|
|
| OG002 | Level 3 - 700mg BID | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. dose for tandtinib is 700mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
|
|
| OG002 | Level 3 - 700mg BID | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. dose for tandtinib is 700mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
|
|
| OG002 | Level 3 - 700mg BID | Phase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. dose for tandtinib is 700mg BID oral tandutinib Pharmacological study Tissue samples tandutinib: Given orally pharmacological study: Correlative studies Tissue samples: Correlative studies |
|
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|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| OG003 | Association Between PFS Biomarker Day 2 / BL | Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation oral tandutinib tandutinib: Given orally pharmacological study: Correlative studies Peripheral blood |
| OG004 | Association Between OS and Biomarker Day 8 / BL | Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation oral tandutinib tandutinib: Given orally pharmacological study: Correlative studies Peripheral blood |
| OG005 | Association Between PFS Biomarker Day 8 / BL | Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation oral tandutinib tandutinib: Given orally pharmacological study: Correlative studies Peripheral blood |
| OG006 | Association Between OS and Biomarker Day 10 /BL | Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation oral tandutinib tandutinib: Given orally pharmacological study: Correlative studies Peripheral blood |
| OG007 | Association Between PFS Biomarker Day 10 / BL | Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation oral tandutinib tandutinib: Given orally pharmacological study: Correlative studies Peripheral blood |
| OG008 | Association Between OS and Biomarker Day 28 / BL | Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation oral tandutinib tandutinib: Given orally pharmacological study: Correlative studies Peripheral blood |
| OG009 | Association Between PFS Biomarker Day 28 / BL | Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation oral tandutinib tandutinib: Given orally pharmacological study: Correlative studies Peripheral blood |
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