Previously-treated Advanced or Metastatic Breast Cancer MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Interventions
Product Name: Pralatrexate
Product Code: PDX
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pralatrexate
CAS Number: 146464-95-1
Current Sponsor code: PDX
Other descriptive name: (RS)
Sponsors
Allos Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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 for at least 28 days prior to study entry. 5. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST): at least 1 uni-dimensionally measurable non-bony target lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) or chest x-ray (= 20 mm with conventional techniques or = 10 mm with spiral CT scan) outside a previously radiated field. 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
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. • Phase 1 only: prior treatment with capecitabine, 5-fluorouracil (5-FU), or antifolates other than methotratrexate is excluded within 6 months prior to enrollment. • 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. 17. Known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 Objective(s): • To determine the maximum tolerated dose (MTD) for pralatrexate up to 190 mg/m2 without vitamins in advanced or metastatic breast cancer patients who have failed prior chemotherapy. Phase 2 Objective(s): • To assess preliminary efficacy of pralatrexate in this patient population.;Secondary Objective: Phase 2 Objective(s): • To evaluate the safety and tolerability of pralatrexate with and without vitamin supplementation in this patient population. • To determine the pharmacokinetic (PK) profile of pralatrexate. • To assess the potential relationships between pralatrexate response and relevant biomarkers and correlate this with dose and plasma PK.;Primary end point(s): Phase 1: • The primary endpoint is whether or not the patient experiences a DLT. (DLT must be treatment-related, and occur in cycle 1) Phase 2: • The primary endpoint is the occurrence of any of the following regardless of when they occur: - = Grade 3 treatment-related hematological AE, excluding anemia, lasting for = 7 days. - = Grade 3 treatment-related neutropenic fever. - = Grade 3 treatment-related non-hematological AE, excluding nausea and vomiting. - Greater than 28 days has elapsed since the last dose of pralatrexate due to treatment-related AEs. | — |
Countries
Czech Republic, France, Hungary
Outcome results
None listed