Imetelstat in Combination With Paclitaxel (With or Without Bevacizumab) in Patients With Locally Recurrent or Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of treatment with imetelstat + paclitaxel (with or without bevacizumab) versus paclitaxel (with or without bevacizumab) alone for patients with locally recurrent or metastatic breast cancer who have not received chemotherapy or have received one non-taxane based chemotherapy for metastatic breast cancer.

Detailed Description
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Patients will be randomized in a 1:1 ratio to imetelstat + paclitaxel (with or without bevacizumab) versus paclitaxel (with or without bevacizumab) alone.

Official Title
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A Randomized Phase II Study Of Imetelstat (GRN163L) In Combination With Paclitaxel (With Or Without Bevacizumab) in Patients With Locally Recurrent Or Metastatic Breast Cancer

Conditions
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Locally Recurrent or Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Imetelstat sodium
* Drug: Bevacizumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically or cytologically confirmed adenocarcinoma of the breast that is either locally recurrent or metastatic. Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent Either have not received chemotherapy or may have had one prior non-taxane chemotherapy regimen for metastatic disease (there are no restrictions on prior hormonal therapy) Prior use of bevacizumab is allowed provided that it was not administered in combination with a taxane ECOG performance status 0-1 Adequate bone marrow reserve as indicated by: ANC > 1500/uL (without use of growth factors within 7 days) Platelet count > 100,000 (without transfusion in prior 7 days) Hemoglobin > 9.0 g/dL Exclusion Criteria: Women who are pregnant or breast feeding Locally recurrent disease amenable to resection with curative intent HER-2-positive breast cancer Active central nervous system (CNS) metastatic disease including those patients receiving radiotherapy and/or steroid treatment (within the last 3 months) Prior adjuvant or neoadjuvant taxane chemotherapy within 12 months prior of first relapse Investigational therapy within 4 weeks of first study drug administration Prior radiation, cytotoxic, or hormonal therapy within 2 weeks of first study drug administration Therapeutic anti-coagulation or regular use of anti-platelet therapy within 2 weeks prior to first study drug administration (low dose anti-coagulant therapy to maintain patency of a vascular access device is allowed) Grade ≥ 2 neuropathy Uncontrolled clinically significant atrial or ventricular arrhythmias (unless pacemaker in place) Severe conduction disturbance including clinically significant QTC prolongation > 450 ms (unless pacemaker in place) Active or chronically recurrent bleeding (e.g., active peptic ulcer disease) Clinically relevant active infection Known positive serology for human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imetelstat + Paclitaxel (with or without bevacizumab)<br> | Drug: Imetelstat sodium<br>* Imetelstat is administered at a dose of 300 mg/m2 on day one of a 21 day cycle.<br>* Other names: GRN163L;Drug: Bevacizumab<br>* Bevacizumab is administered at 15 mg/kg on day one of a 21 day cycle<br>* Other names: Avastin;Drug: Paclitaxel<br>* Paclitaxel is administered at 90 mg/m2 on days one and eight of a 21 day cycle<br>* Other names: Taxol;|
| Experimental: Paclitaxel (with or without bevacizumab) alone<br> | Drug: Bevacizumab<br>* Bevacizumab is administered at 15 mg/kg on day one of a 21 day cycle<br>* Other names: Avastin;Drug: Paclitaxel<br>* Paclitaxel is administered at 90 mg/m2 on days one and eight of a 21 day cycle<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Defined as the time from randomization to documented disease progression, as determined by the investigator's assessment according to RECIST, or death from any cause, whichever occurs first. | Occurring post randomization through end of study period (9 mos. after the last participant is randomized) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response | Objective response as determined by the investigator according to RECIST for patients with measurable disease at baseline. | Occurring post randomization through end of study period (9 mos. after the last participant is randomized) | 
| Clinical benefit rate | Clinical response rate includes patients with objective response and stable disease lasting at least 6 months. | Occurring post randomization through end of study period (9 mos. after the last participant is randomized) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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imetelstat, imetelstat sodium, GRN163L, telomerase inhibitor, telomerase inhibition, metastatic breast cancer, locally recurrent breast cancer, Bevacizumab, Paclitaxel, Avastin, Taxol, HER-2-negative, First-Line Chemotherapy, Second-Line Chemotherapy