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A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis (LMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00527410
Recruitment Status : Terminated (Business Decision)
First Posted : September 10, 2007
Last Update Posted : November 13, 2014
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

Brief Summary:
This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent neoplastic meningitis.

Condition or disease Intervention/treatment Phase
Leptomeningeal Carcinomatosis Drug: RTA 744 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis
Study Start Date : October 2006
Actual Primary Completion Date : December 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: RTA 744
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).
Drug: RTA 744
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 Measures :
  1. 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 ]
  2. 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 Measures :
  1. Document any potential antitumor activity. [ Time Frame: after every even numbered treatment cycle ]
  2. Correlate pharmacokinetic information with clinical (efficacy and safety) responses. [ Time Frame: end of study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00527410

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
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Responsible Party: Reata Pharmaceuticals, Inc. Identifier: NCT00527410    
Other Study ID Numbers: RTA 744-C-0601
First Posted: September 10, 2007    Key Record Dates
Last Update Posted: November 13, 2014
Last Verified: November 2014
Additional relevant MeSH terms:
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Meningeal Carcinomatosis
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site