Phase 2 Study of Pralatrexate in Female Patients with Previously-treated Advanced or Metastatic Breast Cancer

• Conditions: Previously-treated Advanced or Metastatic Breast Cancer; MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer

• Registration Number: EUCTR2008-006425-14-CZ
• Lead Sponsor: Allos Therapeutics, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-26
• Last Update Posted: 26 June 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

Inclusion Criteria:
1. Histologically and/or cytologically confirmed human epidermal growth factor receptor 2 (HER-2) negative advanced or metastatic breast cancer, as shown by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC).
2. Patients must have failed at least 1 prior chemotherapy regimen for advanced or metastatic disease.
3. Patients with advanced or metastatic disease resistant to both a taxane and an anthracycline-containing chemotherapy regimen or resistant to taxanes and for whom further anthracycline therapy is not indicated. Taxane resistance is defined as progressive disease while on or within 3 months from end of treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen.
4. Patients with controlled brain metastases must have completed appropriate radiation therapy and if on corticosteroids, be on a stable or tapering dose of = 10 mg/day prednisone (or equivalent) for at least 28 days prior to study entry.
5. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) (see http://www.eortc.be/recist/).
6. Female = 18 years of age.
7. Eastern Cooperative Oncology Group (ECOG) performance status = 2.
8. Life expectancy > 3 months.
9. Adequate hematological, hepatic, and renal function as defined by: white blood cell (WBC) count = 2500 cells/µL (= 2.5 x 109 cells/L), absolute neutrophil count (ANC) = 1500 cells/µL (= 1.5 x 109 cells/L); platelet count = 100,000/µL (= 100 x 109/L); hemoglobin = 10 g/dL (= 100 g/L); calculated creatinine clearance (CrCl) of = 50 mL/min; total bilirubin = 1.5 x the upper limit of normal (ULN); aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT), and gamma-glutamyltransferase (?-GT) = 3 x ULN (if clearly attributable to liver metastases, ALT/AST/?-GT = 5 x ULN is permitted).
10. Females of childbearing potential have a negative serum pregnancy test within 14 days prior to enrollment and must agree to practice a medically acceptable and effective contraceptive regimen from enrollment until at least 30 days after the last administration of pralatrexate. Patients who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized do not require this test.
11. Accessible for repeat dosing and follow- up.
12. Given written informed consent (IC).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients with bone metastasis only.
2. A single metastatic site without histological proof of the lesion being metastatic breast cancer.
3. Patients with inflammatory breast cancer.
4. Receipt of systemic chemotherapy, hormone therapy, radiation therapy, or other investigational therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C) prior to enrollment, with the following exceptions noted:
• Bisphosphonates are permitted if ongoing.
• Prior treatment with methotrexate is excluded.
• Prior treatment with anti-angiogenics is excluded within 6 months prior to enrollment.
5. Prior treatment with > 2 prior chemotherapy regimens (3 prior chemotherapy regimens are allowed if 1 of the treatments was neoadjuvant or adjuvant chemotherapy).
6. Previous exposure to pralatrexate.
7. Anthracycline maximum cumulative dose exceeded (ie, doxorubicin with no risk factors = 550 mg/m2, otherwise 450 mg/m2; epirubicin = 720 mg/m2).
8. Extensive prior radiation therapy on more than 30% of bone marrow reserve or prior bone marrow/stem cell transplantation.
9. Congestive Heart Failure Class III/IV according to New York Heart Association (NYHA) Functional Classification.
10. Uncontrolled hypertension.
11. Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment.
12. Females who are pregnant or breastfeeding.
13. Major surgery within 14 days of enrollment.
14. Active concurrent primary malignancy (except adequately treated in situ cervical cancer and basal cell skin cancer).
15. Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent or limit study compliance.
16. Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of < 100 mm3 or detectable viral load within past 3 months and is receiving anti-retroviral therapy.
17. Hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified