RTA 744 in Breast Cancer Patients With Progression of Previously Irradiated Brain Metastases

NCT00538343 | Terminated Phase 2

• 1 other identifier: RTA 744-C-0703
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to determine whether RTA 744 is effective in the treatment of breast cancer that has metastasized to the brain.

Conditions

Brain Metastases

Keywords

brain metastases; breast cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of RTA 744 in reducing intracranial tumor on contrast-enhanced MRI of breast cancer patients with progression of brain metastases following whole brain radiotherapy (WBRT).

  21 Days

Secondary Outcomes (7)

• To evaluate the efficacy of RTA 744 on intracranial tumor as measured by intracranial objective response rate (Intracranial ORR) determined by modified RECIST criteria and by volumetric analysis.

  18 weeks

• To evaluate overall objective response rate after administration of RTA 744.

  18 weeks

• To evaluate the efficacy of RTA 744 on intracranial tumor as measured by intracranial Time To Progression.

  18 weeks

• To evaluate progression free survival (PFS) after administration of RTA 744.

  18 weeks

• To evaluate overall survival (OS) after administration of RTA 744.

  18 weeks

Study Arms (1)

RTA 744

EXPERIMENTAL

Drug: berubicin hydrochloride (RTA 744)

Interventions

berubicin hydrochloride (RTA 744) DRUG

RTA 744

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed adenocarcinoma of the breast with at least one evaluable brain lesion ( ≥ 1 cm in one dimension) on contrast-enhanced MRI after WBRT and documented intracranial failure/progression i. Presence of any new lesion(s); or ii. ≥ 25% increase in bi-dimensional measurement of existing tumor
• Definitive radiotherapy ≥ 3000 cGy for documented CNS disease completed ≥ 4 weeks prior to initiation of protocol therapy
• ≥ 2 weeks since stereotactic radiosurgery or gamma knife therapy
• ≥ 4 weeks since neurosurgery (open brain or stereotactic brain biopsy). Patients must have completely recovered from the side effects of surgical procedure.
• ≥ 2 weeks since major surgery (other than neurosurgical procedure) and complete recovery from this surgical procedure.
• Most recent chemotherapeutic treatment regimen completed ≥ 2 weeks prior to study entry provided toxicities have resolved.
• i. Hormone receptor positive patients must have progressed on one prior hormonal AND at least one prior chemotherapy course in the metastatic setting.
• ii. Hormone receptor negative patients must have progressed on at least one prior chemotherapy course in the metastatic setting.
• iii. Her2 positive patients must have progressed on at least one prior chemotherapeutic and one Her2-targeted combination course in the metastatic setting.
• Life expectancy ≥ 12 weeks.
• Patients receiving corticosteroids must have been on a stable dose for 2 weeks prior to study enrollment.
• LVEF ≥ 50% on MUGA or ECHO
• ECOG performance status of 0-2.
• Laboratory values confirmed within 14 days of initiation of study therapy: Granulocytes ≥ 1,500/μL; Lymphocytes ≥ 1,000/μL; Platelets ≥ 100,000/μL; Hemoglobin ≥ 9 gm/dL; Total Bilirubin \< 1.5 times upper limit of normal (ULN); ALT and AST \< 1.5 times ULN (\< 5 times ULN in patients with liver metastases); Creatinine \< 1.5 times ULN
• Women of childbearing potential must have negative serum pregnancy test, and must agree to use adequate contraceptive method during administration of study treatment and for three months after completing treatment.

You may not qualify if:

• Evidence of new or progressive metastatic disease in the brainstem or intramedullary upper spinal cord. (Metastases in the thalamus are allowed).
• Evidence of diffuse leptomeningeal disease on brain MRI or by previously documented CSF cytology. (Discrete dural metastases are permitted.)
• Evidence of impending herniation on baseline MRI.
• Evidence of CNS hemorrhage on baseline MRI (within 14 days of study enrollment).
• Grade 3 or 4 motor, sensory, or cranial neuropathy symptoms; Grade 3 or 4 seizures, headache or nausea/vomiting.
• Evidence of bleeding diathesis, coagulopathy or requirement for therapeutic anticoagulation.
• Total lifetime, cumulative anthracycline dose \> 350 mg/m2.
• Impaired cardiac function or other significant cardiac disease or arrhythmia of any type including: Complete left bundle branch block; Severe aortic stenosis iii. Obligate use of a cardiac pacemaker; ST depression of \> 1mm in ≥ 2 leads and/or T wave inversions in ≥ 2 contiguous leads; Congenital long QT syndrome; History or presence of ventricular or atrial arrhythmia; Clinically significant bradycardia; QTc \> 480 msec on EKG; Uncontrolled hypertension, history of labile hypertension or history of poor compliance with anti-hypertensive regimen; New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF); History of myocardial infarction within the past 6 months within the past 6 months
• Concurrent or recent (within 4 weeks prior to randomization) medication(s) that may interfere with study treatment or results, i.e., immunosuppressants other than corticosteroids, enzyme-inducing anti-epileptics and agents that prolong the QTc.
• Concurrent or planned hormonal, chemotherapeutic, experimental, or targeted biologic therapy.
• Any of the following concurrent severe or uncontrolled medical condition which could compromise participation in the study: Uncontrolled diabetes; Active or uncontrolled infection; Acute or chronic liver disease (i.e. hepatitis, cirrhosis); Patients having a contraindication to MRI imaging
• Pregnant
• Inability to comply with study and/or follow-up procedures.

Sponsors & Collaborators

• Biogen: lead

Study Sites (7)

Palm Beach Cancer Institute

West Palm Beach, Florida, 33401, United States

Location

Presbyterian Health Care

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 25184, United States

Location

Moses Cone Regional Cancer Center

Greensboro, North Carolina, 27403, United States

Location

Forsyth Regional Cancer Center

Winston-Salem, North Carolina, 27103, United States

Location

Texas Oncology, PA

Dallas, Texas, 75246, United States

Location

Virginia Oncology Associates

Newport News, Virginia, 23606, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Breast Neoplasms

Interventions

WP 744

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2007
• First Posted: October 2, 2007
• Study Start: October 31, 2007
• Primary Completion: December 1, 2008
• Study Completion: January 1, 2009
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (7)