Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Gliosarcoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Tumor, Adult

Neuroepithelioma

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

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

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

conventional surgery

tandutinib

pharmacological study

Tissue samples

Tracy Batchelor, MD

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.

Tandutinib in Treating Patients With Recurrent or Progressive Glioblastoma

A Feasibility Assessment and a Phase I/II Trial of MLN518 for Treatment of Patients With Recurrent Glioblastoma

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.

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

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

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

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 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 overall failure rate is expressed as hazard of failure per person-year of follow-up.

Grade 3 or 4 toxicities related to treatment as determined by the CTCAE

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

National Cancer Institute (NCI)

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

Arm I - Feasibility

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

Arm 2 - Dose Escalation (Phase 1)

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

Arm 3 - Phase 2

Arm 1 - Phase 0

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

Arm 2 - Phase 1

Total

Age, Continuous

Sex: Female, Male

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

Karnofsky Performance Status

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

Mini Mental Score

Steroids

all pts had to have confirmed histological GBM, prior treatment wih RT and a MMSE of greater or equal to 15.

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.

Stuart A Grossman, MD Director of ABTC

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. All dose Levels

tandutinib: Given orally

pharmacological study: Correlative studies

Reporting Group - Phase 1

19 patients enrolled in dose escalation but 4 were removed for reasons other than drug related toxicity

Maximum Tolerated Dose of Tandutinib Defined by Dose Limiting Toxicities (Phase 1)

Participants receive oral tandutinib 500 mg twice daily for 7 days prior to surgery. Patients then undergo biopsy or surgery to remove the tumor. Tissue collected for tumor/plasma ratio.

Post surgery, 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. (not necessary for feasibility)

conventional surgery

oral tandutinib

Pharmacological study

Tissue samples

conventional surgery: Undergo surgery

tandutinib: Given orally

pharmacological study: Correlative studies

Tissue samples: Correlative studies

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

To Determine the Tumor/Plasma Ratio of in Subjects With Recurrent GBM Undergoing Resections (Phase 0)

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 500mg BID

oral tandutinib

Pharmacological study

Tissue samples

tandutinib: Given orally

pharmacological study: Correlative studies

Tissue samples: Correlative studies

Level 1 - 500mg 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 600mg BID

oral tandutinib

Pharmacological study

Tissue samples

tandutinib: Given orally

pharmacological study: Correlative studies

Tissue samples: Correlative studies

Level 2 - 600mg 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

Level 3 - 700mg BID

all GBM, All prior treatment with RT. assessment was for 28 days, cycle 1. 3 dose levels 500, 600 and 700mg

Number of Dose Limiting Toxicities Per Dose Level

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)

Tumor Response (Complete Response and Partial Response) Rate (Phase II)

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.

Phase 2: MTD dose Patients receive tandutinib as in phase I at the MTD (600mg BID) determined in phase I.

600mg was the determined MTD in Dose Escalation

dose for tandtinib is 600mg BID

oral tandutinib

Pharmacological study

Tissue samples

tandutinib: Given orally

pharmacological study: Correlative studies

Tissue samples: Correlative studies

Level 2 - 600mg BID (Phase 1 & Phase 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 \<LOQ 8 pts or samples not collected proper times 1pt. 2pts feasibility arm did not restart treatment post-surgery

Pharmacokinetics (Max Concentration of Plasma) for Tandutinib in Phase 1 and Phase 2

Pharmacokinetics (Apparent Terminal Phase Half-life) for Tandutinib in Phase 1 and Phase 2

Pharmacokinetics (Area Under the Plasma Concentration Time Profile From Zero to Infinity (AUC)) for Tandutinib in Phase 1 and Phase 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 \<LOQ 8 pts or samples not collected proper times 1pt. 2pts feasibility arm did not restart treatment post surgery

Pharmacokinetics; Apparent Oral Clearance for Tandutinib in Phase 1 and Phase 2

Pharmacokinetics; Apparent Oral Total Body Volume of Distribution for Tandutinib in Phase 1 and Phase 2

Pharmacokinetics; Steady-state Trough Concentration for Tandutinib in Phase 1 and Phase 2

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.

Overall Survival (Phase II)

The probability of 6-momth progression-free survival will be estimated using binomial distribution.

Six-month Progression-free Survival Rate (Phase II)

Overall Failure Rate (Phase II)

Proportion of Patients With Serious or Life Threatening Toxicities

SDF_1a

bFGF

PIGF

sFLT_1

VEGF

CAIX

VEGFR2

ANG_2

Patients receive tandutinib at 600mg as was the determined MTD in Dose Escalation

oral tandutinib

tandutinib: Given orally

pharmacological study: Correlative studies

Peripheral blood

Baseline (BL) - Overall Survival (OS)

Baseline (BL) - Progression Free Survival (PFS)

Association Between OS and Biomarker Day 2 / BL

Association Between PFS Biomarker Day 2 / BL

Association Between OS and Biomarker Day 8 / BL

Association Between PFS Biomarker Day 8 / BL

Association Between OS and Biomarker Day 10 /BL

Association Between PFS Biomarker Day 10 / BL

Association Between OS and Biomarker Day 28 / BL

Association Between PFS Biomarker Day 28 / BL

peripheral blood was obtained from 20 patients enrolled in the phase 2 portion of the study.

Protein Expression Patterns Post Treatment - Loss or Gain

Arm 1- Phase 0

Overall Study

Digestive System Diseases

Liver Neoplasms

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Liver Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Hematinics

Herbal and Botanical

Anesthetics

Liver Extracts

Cola

Patients will have 10 mL of peripheral venous blood drawn immediately prior to surgery, in the post anesthesia care unit (PACU), and at the first postoperative clinic visit for a total of 30 mL.

blood draws

Three small pieces of otherwise "normal-appearing" liver of 0.5-1 cm3 collected intraoperatively from patients in all four groups (including Group D). Because liver biopsy is less frequently performed during operations for benign colon lesions or Stage I-III colon cancers, this single aspect of the protocol can be made optional at the discretion of the surgical attending or the patient, however bloods and tissue from pathology will still be collected.

colectomy or hepatectomy

This may be done either at a preoperative clinic setting or immediately prior to surgery.

Fibroscan test

Michael D'Angelica

The purpose of this study is to explore novel ways of diagnosing colon cancer and predicting its propensity to spread to other organs such as the liver.

A Study of Imaging, Blood, and Tissue Samples to Guide Treatment of Colon Cancer and Related Liver Tumors

Development of Novel Imaging and Laboratory Biomarkers to Monitor the Liver Pre-metastatic Niche and Guide Treatment of Colon Cancer: A Pilot Study

defined as isolation of at least 5μg of exosomal protein and reported as a binomial proportion with a 95% confidence interval.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tandutinib in Treating Patients With Recurrent or Progressive Glioblastoma	NCT00379080	Adult Brain Tum... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Recurrent Adult...	conventional su... tandutinib pharmacological... Tissue samples	18 Years -	National Cancer Institute (NCI)
A Study of Imaging, Blood, and Tissue Samples to Guide Treatment of Colon Cancer and Related Liver Tumors	NCT03432806	Colon Cancer Liver Tumors	blood draws colectomy or he... Fibroscan test	18 Years -	Memorial Sloan Kettering Cancer Center
Tandutinib in Treating Patients With Recurrent or Progressive Glioblastoma	NCT00379080	Adult Brain Tum... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Recurrent Adult...	conventional su... tandutinib pharmacological... Tissue samples	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for tissue samples