Ixabepilone + Carboplatin Metastatic Breast Cancer

NCT ID: NCT01075100

Last Updated: 2016-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-06-30

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.

Conditions

Metastatic Breast Cancer

Keywords

metastatic; breast; cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Weekly Ixabepilone +carboplatin

Subjects will receive ixabepilone and carboplatin on Days 1 and 8 of each 21-day cycle.

Group Type: EXPERIMENTAL

Ixabepilone

Intervention Type: DRUG

20 mg/m2 on Days 1 and 8

Carboplatin

Intervention Type: DRUG

carboplatin AUC=2.5 on Days 1 and 8

Interventions

Ixabepilone

20 mg/m2 on Days 1 and 8

Intervention Type: DRUG

Carboplatin

carboplatin AUC=2.5 on Days 1 and 8

Intervention Type: DRUG

Other Intervention Names

Ixempra; azaepothilone B; Paraplatin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

US Oncology Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cynthia R Osborne, MD

Role: PRINCIPAL_INVESTIGATOR

US Oncology

Locations

Hematology Oncology Associates

Phoenix, Arizona, United States

Arizona Oncology Associates, PC - NAHOA

Sedona, Arizona, United States

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

Southwest Cancer care

Murrieta, California, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Florida Cancer Institute - New Hope

Hudson, Florida, United States

Melbourne Internal Medicine Associates

Melbourne, Florida, United States

Florida Institute of Research, Medicine & Surgery

Ocoee, Florida, United States

Cancer Care & Hematology Specialists of Chicagoland

Niles, Illinois, United States

Central Indiana Cancer Centers

Carmel, Indiana, United States

Alliance Hematology Oncology, P.A.

Westminster, Maryland, United States

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, United States

Maryland Oncology Hematology, PA The Medical Pavillion at Howard County

Columbia, Missouri, United States

Missouri Cancer Associates

Columbia, Missouri, United States

Kansas City Cancer Center, LLC

Kansas City, Missouri, United States

St. Joseph Oncology, Inc.

Saint Joseph, Missouri, United States

Comprehensive Cancer Care Centers of Nevada

Henderson, Nevada, United States

Hematology-Oncology Associates of Northern NJ, PA Carol G. Simon Cancer Center

Morristown, New Jersey, United States

Ruth Oratz MD

New York, New York, United States

Interlakes Oncology & Hematology, P.C

Rochester, New York, United States

Raleigh Hematology Oncology Associates

Raleigh, North Carolina, United States

Dayton Oncology & Hematology, P.A. Greater Dayton Cancer Center

Kettering, Ohio, United States

Northwest Cancer Specialists, PC

Portland, Oregon, United States

Medical Oncology Associates of Wyoming Valley, PC

Kingston, Pennsylvania, United States

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

Texas Oncology - Abilene

Abilene, Texas, United States

Texas Oncology - Amarillo

Amarillo, Texas, United States

Texas Oncology - Austin Midtown

Austin, Texas, United States

Texas Oncology - Bedford

Bedford, 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

Dallas, Texas, United States

Texas Oncology- Denton South

Denton, Texas, United States

Texas Oncology-Fort Worth 12 Ave

Fort Worth, Texas, United States

Texas Oncology-Memorial City

Houston, Texas, 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

Texas Oncology-Mesquite

Mesquite, Texas, United States

Texas Oncology-Midland Allison Cancer Center

Midland, Texas, United States

Texas Oncology- Odessa West Texas Cancer Center

Odessa, Texas, United States

Paris Regional Cancer Center

Paris, Texas, 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

Texas Cancer Center - Sherman

Sherman, Texas, United States

Texas Oncology - Sugar Land

Sugar Land, Texas, United States

Texas Oncology-Tyler

Tyler, Texas, United States

Texas Oncology-Waco

Waco, Texas, United States

Texas Oncology Wichita Falls Texoma Cancer Center

Wichita Falls, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Highline Medical Oncology

Burien, Washington, United States

Puget Sound Cancer Centers

Edmonds, Washington, United States

Columbia Basin Hematology & Oncology

Kennewick, Washington, United States

Puget Sound Cancer Centers

Seattle, Washington, United States

Cancer Care Northwest

Spokane, Washington, United States

Evergreen Hematology & Oncology

Spokane, Washington, United States

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, United States

Raleigh Regional Cancer Center dba Beckley Oncology Associates Inc.

Beckley, West Virginia, United States

Countries

United States

Other Identifiers

08007

Identifier Type: -

Identifier Source: org_study_id