Clinical trial NCT01256762: Imetelstat in Combination With Paclitaxel (With or Without Bevacizumab) in Patients With Locally Recurrent or Metastatic Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Locally Recurrent or Metastatic Breast Cancer
Keywords: 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
Lead sponsor: Geron Corporation
Sponsor class: INDUSTRY
First posted: 2010-12-09
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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)

Primary outcomes:
measure: Progression-free survival
timeFrame: Occurring post randomization through end of study period (9 mos. after the last participant is randomized)
Secondary outcomes:
measure: Objective response
timeFrame: Occurring post randomization through end of study period (9 mos. after the last participant is randomized)
measure: Clinical benefit rate
timeFrame: Occurring post randomization through end of study period (9 mos. after the last participant is randomized)
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Center
state: Alabama
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Campbell
country: United States
facility: Southbay Oncology Hematology Partners
state: California
city: Fresno
country: United States
facility: Cancer Care Associates
state: California
city: Long Beach
country: United States
facility: Memorial Miller Hospital
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: Palm Springs
country: United States
facility: Desert Regional Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: UC San Diego
state: California
city: Santa Rosa
country: United States
facility: Redwood Regional Medical Group
state: California
city: Aurora
country: United States
facility: Univ. Colorado at Denver
state: Colorado
city: Torrington
country: United States
facility: Connecticut Oncology & Hematology
state: Connecticut
city: Waterbury
country: United States
facility: Medical Oncology Hematology
state: Connecticut
city: Jacksonville
country: United States
facility: Florida Oncology Associates
state: Florida
city: Port St. Lucie
country: United States
facility: Hematology Oncology Associates
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care
state: Georgia
city: Atlanta
country: United States
facility: Peachtree Hematology Oncology
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Macon
country: United States
facility: Central Georgia Cancer Care
state: Georgia
city: Savannah
country: United States
facility: Summit Cancer Care
state: Georgia
city: Post Falls
country: United States
facility: Kootenai Medical Center
state: Idaho
city: Chicago
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Normal
country: United States
facility: Mid Illinois Hematology & Oncology
state: Illinois
city: Zion
country: United States
facility: Cancer Treatment Centers of America
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Community Hospitals of Indiana
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Mount Sterling
country: United States
facility: Montgomery Cancer Care
state: Kentucky
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Albuquerque
country: United States
facility: New Mexico Cancer Center
state: New Mexico
city: Lake Success
country: United States
facility: Prohealth Associates
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Charlotte
country: United States
facility: Carolinas Hematology/Oncology
state: North Carolina
city: Greensboro
country: United States
facility: Moses Cone Medical System
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve Univ.
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Physicians of Oklahoma
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates
state: Oklahoma
city: Portland
country: United States
facility: Kaiser Northwest
state: Oregon
city: Harrisburg
country: United States
facility: Pinnacle Health
state: Pennsylvania
city: Hershey
country: United States
facility: Penn. State Univ.
state: Pennsylvania
city: Germantown
country: United States
facility: The Jones Clinic
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Temple
country: United States
facility: Scott & White Healthcare
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: Newmarket
country: Canada
facility: Stronach Regional Cancer Centre at Southlake
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Services Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Geron Corporation
name: Ted Shih, PharmD
role: STUDY_DIRECTOR
affiliation: Indiana University School of Medicine
name: Kathy Miller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1158/1078-0432.CCR-05-2760.
citation: 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.
citation: Herbert BS, Wright WE, Shay JW. Telomerase and breast cancer. Breast Cancer Res. 2001;3(3):146-9. doi: 10.1186/bcr288. Epub 2001 Feb 22.