A clinical study investigating Taxane Therapy With or Without Bavituximab for the Treatment of HER2-Negative Metastatic Breast Cancer

Conditions: metastatic HER2-negative breast cancer
MedDRA version: 18.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-003780-11-DE

Lead Sponsor: Peregrine Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 553

Inclusion Criteria

1. Written informed consent obtained prior to screening.
2. Females or males at least 18 years of age.
3. Histologically or cytologically documented metastatic HER2-negative breast cancer.
4. Measurable disease per RECIST 1.1 (Phase II; Appendix 2); evaluable disease (Phase III).
5. ECOG performance status of 0 or 1 (Appendix 1).
6. Adequate hematologic function: absolute neutrophil count =1500 cells/µL; hemoglobin =9 g/dL; platelets =100,000/µL.
7. Adequate renal function: serum creatinine =1.8 mg/dL or calculated creatinine clearance >50 mL/min using the Cockcroft-Gault equation.
8. Adequate hepatic function: total bilirubin = upper limit of normal (ULN), serum albumin =3.0 g/dL, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =1.5 × ULN. ALT and/or AST may be =5 × ULN if due to liver metastases. If ALT or AST is >1.5 and =5 × ULN in patients with liver metastases, alkaline phosphatase must be =2.5 × ULN. Patients with Gilbert’s syndrome are allowed if total bilirubin is =2 × ULN and direct bilirubin is =ULN.
9. Prothrombin time (PT) and/or international normalized ratio (INR) =1.5 × ULN and activated partial thromboplastin time (aPTT) =1.5 × ULN if patient is not on anticoagulant therapy (a therapeutic PT and/or INR and aPTT is acceptable if the
patient is on anticoagulants).
10. Patients must have a negative serum human chorionic gonadotropin (hCG) test within 1 week of Day 1 (pregnancy test not required for patients with bilateral oophorectomy and/or hysterectomy or for those patients who are >1 year postmenopausal).
11. All patients of reproductive potential (ie, not surgically sterile or postmenopausal) must agree to use a highly effective method of contraception (<1% failure rate per year) during and 3 months after end of study treatment (female) or during and 6 months after end of study treatment (male).
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 470
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 83

Exclusion Criteria

1. HER2-positive breast cancer.
2. Less than 6 months since last dose of prior adjuvant non-taxane regimen.
3. Less than 12 months since last dose of prior adjuvant taxane-containing regimen.
4. Any chemotherapy regimen for MBC within 3 weeks before Day 1.
5. Known history of bleeding diathesis or coagulopathy (eg, von Willebrand disease or hemophilia).
6. Bleeding
a) Clinically significant bleeding, such as gross hematuria, gastrointestinal bleeding, and hemoptysis within the 6 months before screening, unless the cause has been identified and adequately treated (eg, cystitis, ulcer).
b) Minor biopsy-related bleeding lasting <24 hours and resolved at least 1 week before Day 1 is allowed.
7. Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, arterial thrombosis) within 6 months before screening.
8. Grade 2 or higher peripheral neuropathy (eg, numbness, tingling, and/or pain in distal extremities).
9. Radiotherapy within 1 week preceding Day 1; ongoing acute toxicity from prior radiotherapy.
10. Either symptomatic or clinically active brain metastases (ie, requiring ongoing treatment). Patients are eligible if brain metastases are adequately treated. Patients must be either off corticosteroids, or on a stable or decreasing dose of =10 mg daily prednisone (or equivalent).
11. Major surgery within 4 weeks of Day 1.
12. Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease, active infections).
13. Autoimmune disease, being treated with immunosuppressive drugs (eg, methotrexate or biological agents), or other conditions requiring immunosuppressive therapy (eg, prior allotransplantation).
14. History of hypersensitivity to bavituximab, docetaxel, paclitaxel, or to any of their excipients.
15. Symptomatic coronary artery disease, cerebrovascular accident or transient ischemic attack, myocardial infarction, arterial embolism, or unstable angina pectoris within 6 months of screening.
16. Currently pregnant, nursing, or planning a pregnancy during the study.
17. Investigational therapy within 28 days prior to Day 1.
18. Patient has a condition or is in a situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient’s participation in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To characterize the safety and tolerability of bavituximab plus taxane therapy in patients with MBC<br><br>Exploratory:<br>• to assess immune effects in patients treated with bavituximab in combination with taxane therapy<br>• serum levels of ß2-GP1;Main Objective: To evaluate the efficacy of bavituximab in combination with taxane therapy in patients with MBC;Primary end point(s): Phase II: <br>ORR: percentage of patients whose best overall response is complete or partial response (CR or PR).<br><br>Phase III: <br>PFS;Timepoint(s) of evaluation of this end point: Tumor response will be assessed radiographically every 8 weeks (±3 days) for the first approximately 24 weeks, then every 12 weeks (±3 days) thereafter.

Secondary Outcome Measures