Clinical trial NCT01075100: Ixabepilone + Carboplatin Metastatic Breast Cancer
Official title: Phase II Trial of Ixabepilone Plus Carboplatin in Patients With Metastatic Breast Cancer: The ECLIPSE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: metastatic
breast
cancer
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2010-02-24
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 24 months
Secondary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: 24 months
measure: Progression-free Survival (PFS)
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: 24 months
measure: Time to Response
timeFrame: 24 months
measure: Duration of Response
timeFrame: 30 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Hematology Oncology Associates
state: Arizona
city: Sedona
country: United States
facility: Arizona Oncology Associates, PC - NAHOA
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Murrieta
country: United States
facility: Southwest Cancer care
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Hudson
country: United States
facility: Florida Cancer Institute - New Hope
state: Florida
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates
state: Florida
city: Ocoee
country: United States
facility: Florida Institute of Research, Medicine & Surgery
state: Florida
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Carmel
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Westminster
country: United States
facility: Alliance Hematology Oncology, P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Columbia
country: United States
facility: Maryland Oncology Hematology, PA The Medical Pavillion at Howard County
state: Missouri
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Center, LLC
state: Missouri
city: St. Joseph
country: United States
facility: St. Joseph Oncology, Inc.
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Care Centers of Nevada
state: Nevada
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern NJ, PA Carol G. Simon Cancer Center
state: New Jersey
city: New York
country: United States
facility: Ruth Oratz MD
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology & Hematology, P.C
state: New York
city: Raleigh
country: United States
facility: Raleigh Hematology Oncology Associates
state: North Carolina
city: Kettering
country: United States
facility: Dayton Oncology & Hematology, P.A. Greater Dayton Cancer Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists, PC
state: Oregon
city: Kingston
country: United States
facility: Medical Oncology Associates of Wyoming Valley, PC
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Abilene
country: United States
facility: Texas Oncology - Abilene
state: Texas
city: Amarillo
country: United States
facility: Texas Oncology - Amarillo
state: Texas
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Bedford
country: United States
facility: Texas Oncology - Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Dallas Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Methodist Charlton Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Denton
country: United States
facility: Texas Oncology- Denton South
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth 12 Ave
state: Texas
city: Houston
country: United States
facility: Texas Oncology-Memorial City
state: Texas
city: Lewisville
country: United States
facility: Texas Oncology- Lewisville
state: Texas
city: Longview
country: United States
facility: Texas Oncology-Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: Texas Oncology-McAllen South Second Street
state: Texas
city: Mesquite
country: United States
facility: Texas Oncology-Mesquite
state: Texas
city: Midland
country: United States
facility: Texas Oncology-Midland Allison Cancer Center
state: Texas
city: Odessa
country: United States
facility: Texas Oncology- Odessa West Texas Cancer Center
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas-HOAST
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center - Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology - Sugar Land
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Waco
country: United States
facility: Texas Oncology-Waco
state: Texas
city: Wichita Falls
country: United States
facility: Texas Oncology Wichita Falls Texoma Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Edmonds
country: United States
facility: Puget Sound Cancer Centers
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology & Oncology
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Centers
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Spokane
country: United States
facility: Evergreen Hematology & Oncology
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Beckley
country: United States
facility: Raleigh Regional Cancer Center dba Beckley Oncology Associates Inc.
state: West Virginia
Study officials:
affiliation: US Oncology
name: Cynthia R Osborne, MD
role: PRINCIPAL_INVESTIGATOR
References: