RTA 744 Injection in Patients With Leptomeningeal Disease

NCT00512460 | Terminated Phase 1

• 1 other identifier: 2006-0506
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.The primary objectives of this study are:
2. 2.To determine the tolerability of RTA 744 Injection in patients with leptomeningeal disease (LMD) secondary to any type of primary tumor.
3. 3.In a selected group of 6-10 patients who will receive RTA 744 at or near the maximum tolerated dose (MTD), to characterize the multiple-dose pharmacokinetics of RTA 744 in plasma and CSF.
4. 4.The secondary objectives of this study are:
5. 5.To document any potential antitumor activity of RTA 744 in this patient population.
6. 6.To correlate pharmacokinetic information with clinical (efficacy and safety) responses, as a possible help in selecting appropriate doses for later studies.

Conditions

Neoplastic Meningitis; Solid Tumor; Lymphoma; Leukemia; Brain Tumor

Keywords

Neoplastic Meningitis; Leptomeningeal Disease; Solid Tumor; Lymphoma; Leukemia; Brain Tumor; RTA 744

Outcome Measures

Primary Outcomes (1)

• To study the highest tolerable dose of RTA 744 that can be given to patients with cancer that has spread to the meninges of the brain or the spine.

  3 Years

Secondary Outcomes (1)

• To study the level of effectiveness of RTA 744 on the disease.

  3 Years

Study Arms (1)

RTA 744

EXPERIMENTAL

Drug: RTA 744

Interventions

RTA 744 DRUG

4.8 mg/m\^2 by vein Over 2 Hours On Days 1-3.

RTA 744

Eligibility Criteria

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

You may qualify if:

• Age \>/=18 years.
• Histologic confirmation of primary malignancy at original diagnosis. All primary tumor types may be enrolled into the study (solid tumor, lymphoma, leukemia, or brain malignancy).
• Neoplastic meningitis/leptomeningeal metastasis refractory to conventional intrathecal therapy and defined as presence of tumor cells on cytology after cytospin, OR neuroimaging evidence of leptomeningeal tumor by MRI accompanied by clinical evidence of leptomeningeal tumor.
• Patient is not eligible for higher priority clinical trial.
• If patient had surgical resection prior to enrollment, at least 2 weeks should have elapsed prior to enrollment into the study and patient must have completely recovered from the side effects of such therapy.
• For those patients taking steroid medications, the dose of steroid should be stable for at least 7 days prior to obtaining the Gd-MRI of the brain and spine, if medically feasible.
• Karnofsky Performance Status (KPS) of \>/= 60.
• Laboratory Parameters: 1) Absolute Neutrophil Count (ANC) \>/=1.5 x 10\^9/L; 2) Hemoglobin (Hgb) \>/=9 g/dl; 3) Platelets \>/= 100 x 10\^9/L; 4) AST and ALT \</= 3.0 x Upper Limit of Normal (ULN); 5) Serum bilirubin \</= 1.5 x ULN; 6) Serum creatinine \</= 1.5 x ULN and 24 hour creatinine clearance \>/= 50 ml/min
• Life expectancy of at least 8 weeks based on the judgment of the clinical investigator.
• Written informed consent obtained.

You may not qualify if:

• Concurrent intrathecal or intraventricular therapy for leptomeningeal disease or other malignancy.
• Concurrent oral or intravenous cytotoxic therapy for leptomeningeal disease or other malignancy. Patients who are receiving non-cytotoxic concurrent drug for their malignancy may be allowed on the study, provided that the non-cytotoxic drug was started for at least 4 weeks prior to entry into the study and that no apparent toxicity from the non-cytotoxic drug is evident.
• Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
• Patient has previously received anthracycline therapy up to the following cumulative doses: doxorubicin \>/= 550 mg/m\^2 (\>/= 450 mg/m\^2 if patient has had prior chest radiotherapy), epirubicin \>/= 1000 mg/m\^2 (\>/= 800 mg/m\^2 if prior chest radiation), idarubicin \>/= 150 mg/m\^2 (\>/= 130 mg/m\^2 if prior chest radiotherapy) and daunorubicin \>/= 550 mg/m\^2 (\>/= 400 mg/m\^2 if prior chest radiotherapy).
• Patients on anticonvulsant medications or other types of medications which are known liver-enzyme inducers.
• Patients who are pregnant or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control (such as oral, implantable, or injectable contraceptives ) (Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to administration of RTA 744 Injection)
• Total urinary protein in 24 hours urine collection \> 500 mg
• Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: 1) Uncontrolled diabetes (patients diagnosed with Type 1 or Type 2 diabetes who are currently under treatment by a physician for this condition and are not able to control blood sugars with management for glucose levels above 250 mg/dL). 2) Active or uncontrolled infection. 3) Acute or chronic liver disease (i.e., hepatitis, cirrhosis). 4) Confirmed diagnosis of HIV infection
• Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type, including any of the following: 1) LVEF \< 45% as determined by MUGA scan or echocardiogram. 2) Complete left bundle branch block. 3) Obligate use of a cardiac pacemaker. 4) ST depression of \> 1mm in \>/= 2 leads and/or T wave inversions in \>/= 2 contiguous leads. 5) Congenital long QT syndrome.
• \. (continued) 6) History or presence of ventricular or atrial tachyarrhythmias. 7) Clinically significant resting bradycardia (\< 50 beats per minute). 8) QTc \> 480 msec on screening ECG. 9) Uncontrolled high blood pressure(\>140/90), history of labile hypertension, or history of poor compliance with an antihypertensive regimen. 10) Unstable angina pectoris. 11) Symptomatic congestive heart failure.
• Myocardial infarction \</=6 months prior to starting study drug. Patients with a history of CHF or arrhythmias
• Patients who are taking therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed.)
• Patients who have received the following types of prior or concurrent therapy, or who have not recovered from the toxic effects of such therapy: 1) investigational drugs less than 4 weeks prior to entry on this study. 2) intrathecal chemotherapy within 2 weeks prior to entry into this study. 3) systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine) to entry on this study. 4) radiation therapy within 2 weeks prior to entry on this study. 5) any medication known to cause QT interval prolongation.
• Patients who have had any surgery, including resection of a brain tumor within 2 weeks prior to entry on this study
• Patients unwilling to or unable to comply with the protocol

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Reata Pharmaceuticals, Inc.: collaborator

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Meningeal Carcinomatosis; Lymphoma; Leukemia; Brain Neoplasms; Meningeal Neoplasms

Interventions

WP 744

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Brain Diseases; Central Nervous System Diseases

Study Officials

• Morris D. Groves, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 3, 2007
• First Posted: August 7, 2007
• Study Start: September 1, 2006
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 16, 2016

Record last verified: 2016-05

Locations

US (1)