Ixabepilone + Carboplatin Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01075100
• Other study ID #: 08007
• Status: Completed
• Phase: Phase 2
• First received: January 14, 2010
• Last updated: May 19, 2014
• Start date: January 2010
• Est. completion date: June 2013

Study information

• Verified date: May 2014
• Source: US Oncology Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Ixabepilone
20 mg/m2 on Days 1 and 8
• Carboplatin
carboplatin AUC=2.5 on Days 1 and 8

Locations

Country	Name	City	State
United States	Texas Oncology - Abilene	Abilene	Texas
United States	Texas Oncology - Amarillo	Amarillo	Texas
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Raleigh Regional Cancer Center dba Beckley Oncology Associates Inc.	Beckley	West Virginia
United States	Texas Oncology - Bedford	Bedford	Texas
United States	Highline Medical Oncology	Burien	Washington
United States	Central Indiana Cancer Centers	Carmel	Indiana
United States	Maryland Oncology Hematology, PA The Medical Pavillion at Howard County	Columbia	Missouri
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Texas Oncology	Dallas	Texas
United States	Texas Oncology Medical City Dallas	Dallas	Texas
United States	Texas Oncology-Dallas Presbyterian Hospital	Dallas	Texas
United States	Texas Oncology-Methodist Charlton Cancer Center	Dallas	Texas
United States	Texas Oncology- Denton South	Denton	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Puget Sound Cancer Centers	Edmonds	Washington
United States	Texas Oncology-Fort Worth 12 Ave	Fort Worth	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Comprehensive Cancer Care Centers of Nevada	Henderson	Nevada
United States	Texas Oncology-Memorial City	Houston	Texas
United States	Florida Cancer Institute - New Hope	Hudson	Florida
United States	Kansas City Cancer Center, LLC	Kansas City	Missouri
United States	Columbia Basin Hematology & Oncology	Kennewick	Washington
United States	Dayton Oncology & Hematology, P.A. Greater Dayton Cancer Center	Kettering	Ohio
United States	Medical Oncology Associates of Wyoming Valley, PC	Kingston	Pennsylvania
United States	Texas Oncology- Lewisville	Lewisville	Texas
United States	Texas Oncology-Longview Cancer Center	Longview	Texas
United States	Texas Oncology-McAllen South Second Street	McAllen	Texas
United States	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	Texas Oncology-Mesquite	Mesquite	Texas
United States	Texas Oncology-Midland Allison Cancer Center	Midland	Texas
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Hematology-Oncology Associates of Northern NJ, PA Carol G. Simon Cancer Center	Morristown	New Jersey
United States	Southwest Cancer care	Murrieta	California
United States	Ruth Oratz MD	New York	New York
United States	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Florida Institute of Research, Medicine & Surgery	Ocoee	Florida
United States	Texas Oncology- Odessa West Texas Cancer Center	Odessa	Texas
United States	Paris Regional Cancer Center	Paris	Texas
United States	Hematology Oncology Associates	Phoenix	Arizona
United States	Northwest Cancer Specialists, PC	Portland	Oregon
United States	Raleigh Hematology Oncology Associates	Raleigh	North Carolina
United States	Interlakes Oncology & Hematology, P.C	Rochester	New York
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Cancer Care Centers of South Texas-HOAST	San Antonio	Texas
United States	Puget Sound Cancer Centers	Seattle	Washington
United States	Arizona Oncology Associates, PC - NAHOA	Sedona	Arizona
United States	Texas Cancer Center - Sherman	Sherman	Texas
United States	Cancer Care Northwest	Spokane	Washington
United States	Evergreen Hematology & Oncology	Spokane	Washington
United States	St. Joseph Oncology, Inc.	St. Joseph	Missouri
United States	Texas Oncology - Sugar Land	Sugar Land	Texas
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Texas Oncology-Tyler	Tyler	Texas
United States	Texas Oncology-Waco	Waco	Texas
United States	Alliance Hematology Oncology, P.A.	Westminster	Maryland
United States	Texas Oncology Wichita Falls Texoma Cancer Center	Wichita Falls	Texas
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
US Oncology Research	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		24 months	No
Secondary	Clinical benefit rate (CBR) defined as overall response rate (ORR) [complete response + partial response (CR + PR)] + SD > 6 months		24 months	No
Secondary	Progression-free survival (PFS)		24 months	No
Secondary	Overall survival (OS)		24 months	No
Secondary	Duration of responses, duration of stable disease, time to response and drug toxicity	Toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (version 4.0). Subjects enrolled in this study will be carefully monitored during the entire treatment phase and will be followed as is appropriate. Incidence and type of adverse events, including serious adverse events, will be tabulated and summarized using descriptive statistics. Adverse events that are unrelated to treatment and that occur >30 days after the administration of treatment will not be reported or analyzed.	24 months	No