Ixabepilone + Carboplatin Metastatic Breast Cancer

Phase II Trial of Ixabepilone Plus Carboplatin in Patients With Metastatic Breast Cancer: The ECLIPSE Study

Ixabepilone adds significantly to the antitumor effectiveness of capecitabine in both ER+ and triple negative breast cancer. Ixabepilone has substantial antitumor activity in taxane-refractory patients and novel combinations are needed in this poor prognosis population. Carboplatin in combination with gemcitabine or paclitaxel has activity in metastatic breast cancer (MBC); there is also demonstrated activity of the gemcitabine/carboplatin combination in the ER+ versus triple negative subsets. A Phase I study of ixabepilone plus carboplatin in solid tumor patients demonstrated the safety of this combination at the doses and schedule proposed for this Phase II trial (BMS data on file).

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Ixabepilone; Drug: Carboplatin

Detailed Description

This is a Phase II, open label, nonrandomized, parallel, noncomparative, study of 2 groups (as stratified below). All patients will receive ixabepilone 20 mg/m2 on Days 1 and 8 and carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle. Patients will be stratified by either hormone receptor positive [ER+/PR+/HER2-, ER+/PR-/HER2-, ER-/PR+/HER2-]- (n=50) or triples negative ER-/PR-/HER2- (n=53). If one group fulfills their accrual goal first, registration into that strata will be stopped and only patients meeting stratification requirements for the other group will be registered.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Hematology Oncology Associates
    • Sedona, Arizona, United States, 86336
      • Arizona Oncology Associates, PC - NAHOA
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates, PC - HOPE
  • California
    • Murrieta, California, United States, 92562
      • Southwest Cancer Care
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers
  • Florida
    • Hudson, Florida, United States, 34667
      • Florida Cancer Institute - New Hope
    • Melbourne, Florida, United States, 32901
      • Melbourne Internal Medicine Associates
    • Ocoee, Florida, United States, 34761
      • Florida Institute of Research, Medicine & Surgery
  • Illinois
    • Niles, Illinois, United States, 60714
      • Cancer Care & Hematology Specialists of Chicagoland
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Central Indiana Cancer Centers
  • Maryland
    • Westminster, Maryland, United States, 21157
      • Alliance Hematology Oncology, P.A.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, P.A.
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
    • Columbia, Missouri, United States, 21044
      • Maryland Oncology Hematology, PA The Medical Pavillion at Howard County
    • Kansas City, Missouri, United States, 64131
      • Kansas City Cancer Center, LLC
    • St. Joseph, Missouri, United States, 64507
      • St. Joseph Oncology, Inc.
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Care Centers of Nevada
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Hematology-Oncology Associates of Northern NJ, PA Carol G. Simon Cancer Center
  • New York
    • New York, New York, United States, 10016
      • Ruth Oratz MD
    • Rochester, New York, United States, 14623
      • Interlakes Oncology & Hematology, P.C
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Hematology Oncology Associates
  • Ohio
    • Kettering, Ohio, United States, 45409
      • Dayton Oncology & Hematology, P.A. Greater Dayton Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Northwest Cancer Specialists, PC
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • Medical Oncology Associates of Wyoming Valley, PC
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas
  • Texas
    • Abilene, Texas, United States, 79606
      • Texas Oncology - Abilene
    • Amarillo, Texas, United States, 79106
      • Texas Oncology - Amarillo
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin Midtown
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford
    • Dallas, Texas, United States, 75231
      • Texas Oncology-Dallas Presbyterian Hospital
    • Dallas, Texas, United States, 75246
      • Texas Oncology
    • Dallas, Texas, United States, 75237
      • Texas Oncology-Methodist Charlton Cancer Center
    • Dallas, Texas, United States, 75230
      • Texas Oncology Medical City Dallas
    • Denton, Texas, United States, 76210
      • Texas Oncology- Denton South
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology-Fort Worth 12 Ave
    • Houston, Texas, United States, 77024
      • Texas Oncology-Memorial City
    • Lewisville, Texas, United States, 75067
      • Texas Oncology- Lewisville
    • Longview, Texas, United States, 75601
      • Texas Oncology-Longview Cancer Center
    • McAllen, Texas, United States, 78509
      • Texas Oncology-McAllen South Second Street
    • Mesquite, Texas, United States, 75150
      • Texas Oncology-Mesquite
    • Midland, Texas, United States, 79701
      • Texas Oncology-Midland Allison Cancer Center
    • Odessa, Texas, United States, 79761
      • Texas Oncology- Odessa West Texas Cancer Center
    • Paris, Texas, United States, 75460
      • Paris Regional Cancer Center
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas-HOAST
    • Sherman, Texas, United States, 75090
      • Texas Cancer Center - Sherman
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology - Sugar Land
    • Tyler, Texas, United States, 75702
      • Texas Oncology-Tyler
    • Waco, Texas, United States, 76712
      • Texas Oncology-Waco
    • Wichita Falls, Texas, United States, 76310
      • Texas Oncology Wichita Falls Texoma Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Burien, Washington, United States, 98166
      • Highline Medical Oncology
    • Edmonds, Washington, United States, 98026
      • Puget Sound Cancer Centers
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology & Oncology
    • Seattle, Washington, United States, 98133
      • Puget Sound Cancer Centers
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology & Oncology
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital/North Star Lodge
  • West Virginia
    • Beckley, West Virginia, United States, 25801
      • Raleigh Regional Cancer Center dba Beckley Oncology Associates Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Male or female patients will be eligible for inclusion in this study if they meet all of the following criteria:

1. Has measurable metastatic and or locally unresectable breast cancer with documented HER2 negative (-) disease
2. Has at least 1 measurable lesion per RECIST criteria (lesions that can be accurately measured in at least 1 dimension (longest diameter (LD) to be recorded) as ≥20 mm with conventional techniques (CT, MRI, X-ray) or as ≥10 mm with spiral CT scan). Irradiated lesions cannot be used to assess response but can be used to assess progression.

3. Has received up to 2 (0 to 2) prior chemotherapy regimens for metastatic disease with the following conditions:

   •Has had no prior treatment with ixabepilone or platinum agents

4. Has had no adjuvant chemotherapy within the 6 months prior to study, but may have received prior anthracyclines and/or taxanes as adjuvant chemotherapy
5. 3 weeks or more have elapsed since last chemotherapy treatment and any related toxicities have resolved to <Grade 1; at least 30 days must have passed since any investigational product has been administered and associated toxicities must have resolved to <Grade 1 (if applicable).
6. Has an ECOG Performance Status (PS) 0-2
7. Is ≥18 years of age
8. Has a life expectancy of at least 12 weeks

9. Has laboratory values of:

   White blood cell (WBC) count ≥3000 x 106/L Absolute neutrophil count (ANC) ≥1500 x 106/L Hemoglobin ≥9 g/dL Total bilirubin ≤1x upper limit of normal (ULN) AST and ALT ≤2.5 x ULN Alkaline phosphatase ≤2.5 x ULN; up to 5xULN if elevation is due to bone disease Serum creatinine ≤1.5 mg/dL Calculated creatinine clearance >50 mL/min (based on Cockroft and Gault method [Appendix III]) Platelet count ≥100,000 x 106/L

10. If patient has had radiation therapy, it has been completed >3 weeks prior to the start of study treatment. NOTE: Previously irradiated lesions will not be evaluable. However, these patients will still be eligible.
11. Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential [not surgically sterilized and between menarche and 1 year postmenopause
12. If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 3 months thereafter
13. Has signed the most recent Patient Informed Consent Form
14. Has signed a Patient Authorization Form Note: Having tissue available is not an inclusion criterion in this study; however, available tissue will be collected (see Section 8) if possible.

Exclusion Criteria:

A patient will be excluded from this study if he or she meets any of the following criteria:

1. Had prior treatment with ixabepilone or other epothilones
2. Had prior radiation to ≥30% of major bone marrow containing areas (pelvis, lumbar spine)
3. Has ER+ and/or PR+ disease that has not progressed on hormone therapy, unless the patient has life-threatening or rapidly progressing visceral disease
4. Has HER2+ disease (IHC staining of 3+ [uniform, intense membrane staining of >30% of invasive tumor cells]), a FISH result of more than 6 HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals of >2.2)
5. Has only lytic bone disease or nonmeasurable disease only
6. Has a known, prior, severe (NCI CTCAE Grade 3-4) history of hypersensitivity reaction to a drug formulated in Cremophor®EL (polyoxyethylated castor oil) or has history of severe allergic reactions to cisplatin or other platinum-containing compounds
7. Has been treated previously with a platinum-containing agent
8. Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Washout periods for these prior therapies are specified in Section 5.
9. Is receiving concurrent investigational therapy or has received such therapy within the 30 days prior to dosing Day 1
10. Has neuropathy (motor or sensory) >Grade 1
11. Has evidence of CNS involvement requiring radiation or steroid treatment. Patients with stable brain metastases who are off steroids at least 2 weeks are eligible.
12. Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection
13. Has clinically relevant coagulopathy either secondary to hepatic dysfunction or an underlying condition requiring therapeutic anticoagulation (specifically, A-fib, history of DVT). A daily aspirin or Plavix for CAD are permitted.
14. Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs
15. Is a pregnant or breast feeding woman
16. Is unable to comply with the requirements of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Weekly Ixabepilone +carboplatin; Subjects will receive ixabepilone and carboplatin on Days 1 and 8 of each 21-day cycle.	Drug: Ixabepilone; 20 mg/m2 on Days 1 and 8; Other Names: Ixempra; azaepothilone B; Drug: Carboplatin; carboplatin AUC=2.5 on Days 1 and 8; Other Names: Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Evaluate the objective response rate calculated as CR+ PR in the population evaluable for response, as well as the 2 subgroups (hormone receptor positive [ER+/PR+/HER2-, ER+/PR-/HER2-, ER-/PR+/HER2-]) and ER-/PR-HER2-, separately). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate (CBR)	Clinical benefit rate (CBR) defined as objective response rate (ORR, CR + PR) + SD >= 6 months	24 months
Progression-free Survival (PFS)	PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	24 months
Overall Survival (OS)	OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.	24 months
Time to Response	For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response.	24 months
Duration of Response	The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.	30 months

Collaborators and Investigators

• Sponsor: US Oncology Research
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Cynthia R Osborne, MD, US Oncology

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: January 14, 2010
• First Submitted That Met QC Criteria: February 23, 2010
• First Posted (ESTIMATE): February 24, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): December 7, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: cancer; breast; metastatic
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: 08007