Leptomeningeal CarcinomatosisPhase 1LMDNCT00527410
A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis
A Phase 1 study testing RTA 744 in people with Leptomeningeal Carcinomatosis, run by Biogen at 1 site in United States.
Trial summary
This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent neoplastic meningitis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leptomeningeal Carcinomatosis
- What is being tested?
- RTA 744
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2006to 1 Dec 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis
This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent neoplastic meningitis.
Read the 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.
- Conditions
- Leptomeningeal Carcinomatosis
- Being tested
- RTA 744
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RTA 744Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| RTA 744 | Experimental | 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). Receives: Drug: RTA 744 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the tolerability of RTA 744 Injection in patients with leptomeningeal disease (LMD) secondary to any type of primary tumor.
Measured: evaluation at end of cycle 1 for each cohort
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).
Measured: end of study
Secondary outcomes (2)
Document any potential antitumor activity.
Measured: after every even numbered treatment cycle
Correlate pharmacokinetic information with clinical (efficacy and safety) responses.
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2007 (estimated)
- Study start31 Oct 2006
- Primary completion1 Dec 2008
Why it stopped: Business Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal CarcinomatosisStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00527410
- Sponsor's protocol ID
- RTA 744-C-0601
- Acronym
- LMD
- Status last verified
- May 2025
- First submitted
- 7 Sep 2007
- Last updated
- 30 May 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis
- ClinicalTrials.gov ID
- NCT00527410
- Acronym / sponsor ID
- LMD / RTA 744-C-0601
- Conditions
- Leptomeningeal Carcinomatosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Decision
- Enrolment
- 9 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 31 Oct 2006 (actual)
- Primary completion
- 1 Dec 2008 (actual)
- First posted
- 10 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RTA 744 | Experimental | Drug: RTA 744RTA 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RTA 744Aqueous 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. | Drug | RTA 744 |
Primary outcome
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
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
2 secondary outcomes
Document any potential antitumor activity.
Time frame: after every even numbered treatment cycle
Correlate pharmacokinetic information with clinical (efficacy and safety) responses.
Time frame: end of study
Results and safety
The study was stopped early (reason given: Business Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2025.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RTA 744 in people with Leptomeningeal Carcinomatosis, run by Biogen at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2025.