Tandutinib in Treating Patients With Recurrent or Progressive Glioblastoma

NCT00379080 | Completed Phase 1 Results DMC

• 5 other identifiers: NCI-2009-00681CDR0000495253NABTT 0504NABTT-0504U01CA137443
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (10)

• 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

  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

Secondary Outcomes (5)

• Overall Survival (Phase II)

  Up to 4 years

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

  At 6 months

• Overall Failure Rate (Phase II)

  up to 4 years

• Proportion of Patients With Serious or Life Threatening Toxicities

  2 year period

• Protein Expression Patterns Post Treatment - Loss or Gain

  baseline - cycle 2 (28 days)

Study Arms (3)

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

Procedure: conventional surgery; Drug: tandutinib; Other: pharmacological study; Other: 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

Drug: tandutinib; Other: pharmacological study; Other: 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

Drug: tandutinib; Other: pharmacological study; Other: Tissue samples

Interventions

conventional surgery PROCEDURE

Undergo surgery

Also known as: MLN518

Arm I - Feasibility

tandutinib DRUG

Given orally

Also known as: CT53518

Arm 2 - Dose Escalation (Phase 1); Arm 3 - Phase 2; Arm I - Feasibility

pharmacological study OTHER

Correlative studies

Arm 2 - Dose Escalation (Phase 1); Arm 3 - Phase 2; Arm I - Feasibility

Tissue samples OTHER

Correlative studies

Arm 2 - Dose Escalation (Phase 1); Arm 3 - Phase 2; Arm I - Feasibility

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Criteria: * Histologically confirmed glioblastoma: * Progressive or recurrent disease after prior radiotherapy (with or without chemotherapy) * Patients with a previous low-grade glioma that progressed after prior radiotherapy (with or without chemotherapy) and are found to have glioblastoma by biopsy are eligible * 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: * Planning to undergo surgical resection or biopsy * Stereotactic biopsy for confirmation of tumor progression or differentiation of tumor progression from treatment-induced effects allowed * Corticosteroids must be tapered to the lowest required steroid dose and patient must be maintained on a stable dose after surgery or biopsy * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma; Gliosarcoma

Interventions

tandutinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Limitations and Caveats

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.

Results Point of Contact

• Title: Stuart A Grossman, MD Director of ABTC
• Organization: Adult Brain Tumor Consortium

grossman@jhmi.edu

410-955-8837

Study Officials

• Tracy Batchelor, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2006
• First Posted: September 21, 2006
• Study Start: January 1, 2007
• Primary Completion: September 1, 2012
• Study Completion: June 1, 2013
• Last Updated: April 7, 2017
• Results First Posted: April 7, 2017

Record last verified: 2017-02

Locations

US (9)