Back to resultsA Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis (LMD)
Primary Purpose
Leptomeningeal Carcinomatosis
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RTA 744
Sponsored by
About this trial
This is an interventional treatment trial for Leptomeningeal Carcinomatosis
Eligibility Criteria
Inclusion Criteria:
- Histologic confirmation of primary malignancy. All primary tumor types may be enrolled.
- Neoplastic meningitis/leptomeningeal metastasis refractory to conventional therapy with presence of tumor cells on cytology, OR neuroimaging evidence of leptomeningeal tumor by MRI.
- Not eligible for higher priority clinical trial.
- Have recovered from side effects of any surgical resection.
- A stable dose of steroid for at least 7 days prior to the Gd-MRI.
- Karnofsky Performance Status (KPS) of ≥ 60.
- Laboratory Parameters: ANC ≥ 1.5 x 109/L; Hgb ≥ 9 g/dl; Platelets ≥ 100 x 109/L; AST and ALT ≤ 3.0 x ULN; Serum bilirubin ≤ 1.5 x ULN; Serum creatinine ≤ 1.5 x ULN; 24 hour creatinine clearance ≥ 50 ml/min
- Life expectancy of at least 8 weeks.
- Written informed consent obtained.
Exclusion Criteria:
- Concurrent therapy for leptomeningeal disease or other malignancy.
- Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
- Cumulative doses: doxorubicin > 450 - 550 mg/m2, epirubicin > 800-1000 mg/m2, idarubicin >130-150 mg/m2 and daunorubicin > 400-550 mg/m2.
- Anticonvulsant medications or other types of medications which are known to induce the CYP450 enzymes.
- Pregnancy or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control
- Total 24 hour urinary protein > 500 mg.
- Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
- Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type
- Myocardial infarction ≤ 6 months prior
- History of CHF or arrhythmias
- Therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed)
- Investigational drugs less than 4 weeks prior; intrathecal chemotherapy within 2 weeks prior; systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine); radiation therapy within 2 weeks prior; any medication known to cause QT interval prolongation
- Any surgery <2 weeks prior
Sites / Locations
- University of Texas MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RTA 744
Arm Description
RTA 744 injection administered intravenously for a maximum of 18 cycles (54 weeks). Dose escalation based on four dose levels and occurance of dose limiting toxicity (DLT).
Outcomes
Primary Outcome Measures
Determine the tolerability of RTA 744 Injection in patients with leptomeningeal disease (LMD) secondary to any type of primary tumor.
Characterize the multiple-dose pharmacokinetics of RTA 744 in plasma and CSF in a selected group of 6-10 patients who will receive RTA 744 at or near the maximum tolerated dose (MTD).
Secondary Outcome Measures
Document any potential antitumor activity.
Correlate pharmacokinetic information with clinical (efficacy and safety) responses.
Full Information
NCT ID
NCT00527410
First Posted
September 7, 2007
Last Updated
November 12, 2014
Sponsor
Reata Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00527410
Brief Title
A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis
Acronym
LMD
Official Title
A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Terminated
Why Stopped
Business Decision
Study Start Date
October 2006 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Reata Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent neoplastic meningitis.
Detailed Description
Neoplastic meningitis refers to the deposition of malignant cells in the lining (leptomeninges) of the brain and spine. Neoplastic meningitis from solid tumors most often occurs in patients with advanced systemic disease who have failed prior chemotherapy; it is also frequent in patients with CNS parenchymal metastasis. Patient survival remains low, and better treatments are needed to penetrate the blood brain barrier and treat the entire neuraxis.
RTA 744 is a close chemical analogue of the well characterized anti-cancer agent doxorubicin. Unlike doxorubicin, RTA 744 has shown ability to cross the blood brain barrier and to achieve high concentration in CNS tumor tissue in animal models. Dose escalation will continue as pre-determined until first occurrence of a dose-limiting toxicity. Maximum tolerated dose will be determined as defined in protocol.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leptomeningeal Carcinomatosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RTA 744
Arm Type
Experimental
Arm Description
RTA 744 injection administered intravenously for a maximum of 18 cycles (54 weeks). Dose escalation based on four dose levels and occurance of dose limiting toxicity (DLT).
Intervention Type
Drug
Intervention Name(s)
RTA 744
Intervention Description
Aqueous solution of RTA 744 is packaged in 5 ml vials - 1 mg/ ml. The drug is mixed in D10W and infused over 2 hours on three consecutive days.
Primary Outcome Measure Information:
Title
Determine the tolerability of RTA 744 Injection in patients with leptomeningeal disease (LMD) secondary to any type of primary tumor.
Time Frame
evaluation at end of cycle 1 for each cohort
Title
Characterize the multiple-dose pharmacokinetics of RTA 744 in plasma and CSF in a selected group of 6-10 patients who will receive RTA 744 at or near the maximum tolerated dose (MTD).
Time Frame
end of study
Secondary Outcome Measure Information:
Title
Document any potential antitumor activity.
Time Frame
after every even numbered treatment cycle
Title
Correlate pharmacokinetic information with clinical (efficacy and safety) responses.
Time Frame
end of study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologic confirmation of primary malignancy. All primary tumor types may be enrolled.
Neoplastic meningitis/leptomeningeal metastasis refractory to conventional therapy with presence of tumor cells on cytology, OR neuroimaging evidence of leptomeningeal tumor by MRI.
Not eligible for higher priority clinical trial.
Have recovered from side effects of any surgical resection.
A stable dose of steroid for at least 7 days prior to the Gd-MRI.
Karnofsky Performance Status (KPS) of ≥ 60.
Laboratory Parameters: ANC ≥ 1.5 x 109/L; Hgb ≥ 9 g/dl; Platelets ≥ 100 x 109/L; AST and ALT ≤ 3.0 x ULN; Serum bilirubin ≤ 1.5 x ULN; Serum creatinine ≤ 1.5 x ULN; 24 hour creatinine clearance ≥ 50 ml/min
Life expectancy of at least 8 weeks.
Written informed consent obtained.
Exclusion Criteria:
Concurrent therapy for leptomeningeal disease or other malignancy.
Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
Cumulative doses: doxorubicin > 450 - 550 mg/m2, epirubicin > 800-1000 mg/m2, idarubicin >130-150 mg/m2 and daunorubicin > 400-550 mg/m2.
Anticonvulsant medications or other types of medications which are known to induce the CYP450 enzymes.
Pregnancy or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control
Total 24 hour urinary protein > 500 mg.
Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type
Myocardial infarction ≤ 6 months prior
History of CHF or arrhythmias
Therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed)
Investigational drugs less than 4 weeks prior; intrathecal chemotherapy within 2 weeks prior; systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine); radiation therapy within 2 weeks prior; any medication known to cause QT interval prolongation
Any surgery <2 weeks prior
Facility Information:
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
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A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis
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