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

This study has been terminated.
(Business Decision)
Sponsor:
Information provided by:
Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00527410
First received: September 7, 2007
Last updated: February 17, 2009
Last verified: February 2009
  Purpose

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


Condition Intervention Phase
Leptomeningeal Carcinomatosis
Drug: RTA 744
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Reata Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Document any potential antitumor activity. [ Time Frame: after every even numbered treatment cycle ] [ Designated as safety issue: No ]
  • Correlate pharmacokinetic information with clinical (efficacy and safety) responses. [ Time Frame: end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: October 2006
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00527410

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Reata Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00527410     History of Changes
Other Study ID Numbers: RTA 744-C-0601
Study First Received: September 7, 2007
Last Updated: February 17, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Meningitis
Carcinoma
Meningeal Carcinomatosis
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on July 22, 2014