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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Locally Recurrent or Metastatic Breast Cancer	Drug: Imetelstat sodium; Drug: Bevacizumab; Drug: Paclitaxel	Phase 2

Detailed Description:

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	166 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	November 2010
Actual Primary Completion Date :	October 2012
Actual Study Completion Date :	December 2012

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Imetelstat + Paclitaxel (with or without bevacizumab)	Drug: Imetelstat sodium; Imetelstat is administered at a dose of 300 mg/m2 on day one of a 21 day cycle.; Other Name: GRN163L Drug: Bevacizumab; Bevacizumab is administered at 15 mg/kg on day one of a 21 day cycle; Other Name: Avastin Drug: Paclitaxel; Paclitaxel is administered at 90 mg/m2 on days one and eight of a 21 day cycle; Other Name: Taxol
Experimental: Paclitaxel (with or without bevacizumab) alone	Drug: Bevacizumab; Bevacizumab is administered at 15 mg/kg on day one of a 21 day cycle; Other Name: Avastin Drug: Paclitaxel; Paclitaxel is administered at 90 mg/m2 on days one and eight of a 21 day cycle; Other Name: Taxol

Outcome Measures

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Primary Outcome Measures :

1. Progression-free survival [ Time Frame: Occurring post randomization through end of study period (9 mos. after the last participant is randomized) ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

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  Show 55 Study Locations

Sponsors and Collaborators

Geron Corporation

Investigators

Study Director:	Ted Shih, PharmD	Geron Corporation
Principal Investigator:	Kathy Miller, MD	Indiana University School of Medicine

More Information

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Publications:

Hochreiter AE, Xiao H, Goldblatt EM, Gryaznov SM, Miller KD, Badve S, Sledge GW, Herbert BS. Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer. Clin Cancer Res. 2006 May 15;12(10):3184-92.

Goldblatt EM, Gentry ER, Fox MJ, Gryaznov SM, Shen C, Herbert BS. The telomerase template antagonist GRN163L alters MDA-MB-231 breast cancer cell morphology, inhibits growth, and augments the effects of paclitaxel. Mol Cancer Ther. 2009 Jul;8(7):2027-35. doi: 10.1158/1535-7163.MCT-08-1188. Epub 2009 Jun 9.

Herbert BS, Wright WE, Shay JW. Telomerase and breast cancer. Breast Cancer Res. 2001;3(3):146-9. Epub 2001 Feb 22. Review.

Responsible Party:	Geron Corporation
ClinicalTrials.gov Identifier:	NCT01256762 History of Changes
Other Study ID Numbers:	CP14B014
First Posted:	December 9, 2010
Last Update Posted:	January 26, 2016
Last Verified:	December 2015

Keywords provided by Geron Corporation:

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents	Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors