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

Purpose

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	Intervention	Phase
Locally Recurrent or Metastatic Breast Cancer	Drug: Imetelstat sodium Drug: Bevacizumab Drug: Paclitaxel	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Paclitaxel Bevacizumab

U.S. FDA Resources

Further study details as provided by Geron Corporation:

Primary Outcome Measures:

Progression-free survival [ Time Frame: Occurring post randomization through end of study period (9 mos. after the last participant is randomized) ] [ Designated as safety issue: No ]
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:

Objective response [ Time Frame: Occurring post randomization through end of study period (9 mos. after the last participant is randomized) ] [ Designated as safety issue: No ]
Objective response as determined by the investigator according to RECIST for patients with measurable disease at baseline.
Clinical benefit rate [ Time Frame: Occurring post randomization through end of study period (9 mos. after the last participant is randomized) ] [ Designated as safety issue: No ]
Clinical response rate includes patients with objective response and stable disease lasting at least 6 months.


Enrollment:	166
Study Start Date:	November 2010
Study Completion Date:	December 2012
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01256762

Show 55 Study Locations

Sponsors and Collaborators

Geron Corporation

Investigators


Study Director:	Ted Shih, PharmD	Geron Corporation
Principal Investigator:	Kathy Miller, MD	Indiana University Simon Cancer Center

More Information

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
Study First Received:	December 2, 2010
Last Updated:	January 27, 2013
Health Authority:	United States: Food and Drug Administration

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 Breast Diseases Neoplasms Neoplasms by Site Skin Diseases Bevacizumab Paclitaxel Angiogenesis Inhibitors Angiogenesis Modulating Agents Antimitotic Agents	Antineoplastic Agents Antineoplastic Agents, Phytogenic Growth Inhibitors Growth Substances Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses Tubulin Modulators

ClinicalTrials.gov processed this record on March 01, 2015