A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer

Breast Cancer Clinical Trial

— TITAN  

Official title:

Phase III Study of Doxorubicin/Cyclophosphamide (AC) Followed by Ixabepilone vs. AC Followed by Paclitaxel in Patients With Triple-Negative Early-Stage Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00789581
• Other study ID #: SCRI BRE 145
• Secondary ID: TITAN
• Status: Active, not recruiting
• Phase: Phase 3
• First received: November 11, 2008
• Last updated: June 1, 2016
• Start date: January 2009
• Est. completion date: December 2016

Study information

• Verified date: June 2016
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a randomized, Phase III, open-label, multicenter study.

Description:

Patients will be randomized in a 1:1 ratio to receive one of two different treatment arms. Patients in treatment arm 1 will receive AC followed by ixabepilone. Patients in treatment arm 2 will receive AC followed by weekly paclitaxel.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 614
• Est. completion date: December 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Female patients greater than or equal to18 years of age.

2. Histologically confirmed invasive unilateral breast cancer (regardless of

histology).

3. Early-stage breast cancer, defined as:

• Node-positive disease: >0.2-mm metastasis in at least one lymph node (pN1mipN2b)OR

• Node-negative, with primary tumor >1.0 cm (T1c-T3).

4. Definitive loco-regional surgery must have been completed as specified

below:

• Patients must have undergone either breast conservation surgery

(i.e., lumpectomy) or total mastectomy.

• Surgical margins of the resected section must be histologically free of

invasive adenocarcinoma and ductal carcinoma in situ.

• Surgical margins involved with lobular carcinoma in situ (LCIS) will not

be considered as a positive margin; therefore, such patients will be eligible for this study without additional resection.

• Patients must have completed axillary lymph node sampling for the pathologic evaluation of axillary lymph nodes as specified below:

Sentinel node biopsy and/or either lymph node sampling procedure or axillary dissection.

5. Multicentric and multifocal invasive breast cancer is eligible if loco-regional surgery has been completed as described above.

6. Patients with synchronous bilateral cancers are eligible only if:

• All cancers are of triple-negative phenotype, defined as ER-, PR-, HER2-.

• Eligibility based on the highest stage grouping.

7. HER2 negative tumors. HER2 negativity must be confirmed by one of the

following:

• FISH-negative (FISH ratio <2.2), or

• IHC 0-1+, or

• IHC 2-3+ AND FISH-negative (FISH ratio <2.2).

8. Estrogen receptor negative (<10% staining by IHC for estrogen receptor).

9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

10. Patient must be <= 84 days from having completed definitive primary breast surgery (either lumpectomy or mastectomy).

11. MammoSite brachytherapy radiation is acceptable if it is performed

immediately following surgery and prior to chemotherapy. It is recommended that chemotherapy be started no earlier than 2 weeks following the removal of the MammoSite balloon catheter.

12. Adequate hematologic function, defined by:

• Absolute neutrophil count (ANC) >1500/mm3

• Platelet count >=100,000/mm3

• Hemoglobin >9 g/dL

13. Adequate liver function, defined by:

• AST and ALT <=2.5 x the upper limit of normal (ULN)

• Total bilirubin <=1.5 x ULN (unless the patient has grade 1 bilirubin

elevation due to Gilbert's disease or a similar syndrome involving slow

conjugation of bilirubin).

14. Adequate renal function, defined by:

• Serum creatinine <=1.5 x ULN

15. Complete staging work-up <=12 weeks prior to initiation of study treatment

with computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), and either a positron emission tomography (PET) scan or a bone scan.

16. Adequate cardiac function, defined by a left ventricular ejection fraction

(LVEF) value of >50% (or normal per institutional guidelines) by MUGA scan or echocardiogram (ECHO).

17. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (i.e., sentinel node biopsy, port-acath (placement); at least 3 weeks must have elapsed from the time of a major surgery (i.e., lumpectomy, partial or total mastectomy, axillary lymph node dissection, breast reconstruction procedure).

18. Patients with previous history of invasive cancers (including breast cancer)

are eligible if definitive treatment was completed more than 5 years prior to

initiating current study treatment, and there is no evidence of recurrent disease.

19. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.

20. Patient must be accessible for treatment and follow-up.

21. Women of childbearing potential must agree to use an acceptable method of birth control to avoid pregnancy for the duration of study treatment, and for 3 months thereafter.

22. All patients must be able to understand the investigational nature of the

study and give written informed consent prior to study entry.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.

2. History of previous diagnosis of invasive breast cancer (unless treated >5 years previously with no recurrence). History of previously treated ductal carcinoma in situ (DCIS) is acceptable.

3. Any evidence or suspicion of metastatic disease other than ipsilateral

axillary lymph nodes.

4. Any tumor >=T4 (cutaneous invasion, deep adherence, inflammatory breast cancer).

5. Previous anthracycline chemotherapy.

6. Concurrent use of CYP3A4 inhibitors from 72 hours prior to initiation of

study treatment until the end of treatment with ixabepilone.

7. Previous treatment for this breast cancer (including neoadjuvant

chemotherapy).

8. Previous cancer (with the exception of non-melanoma skin cancer or cervical carcinoma in situ) in the past 5 years (including invasive contralateral breast cancer).

9. Peripheral neuropathy of > grade 1 per NCI CTCAE v3.0.

10. Cardiac disease, including: congestive heart failure (CHF) > Class II per

New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

11. History of hypersensitivity to CremophorEL (polyoxyethylated castor oil) or

a drug formulated in CremophorEL such as paclitaxel.

12. Use of any investigational agent within 30 days of administration of the first dose of study drug.

13. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.

14. Concurrent severe, uncontrolled infection or intercurrent illness including,

but not limited to, ongoing or active infection, or psychiatric illness/social

situations that would limit compliance with study requirements.

15. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.

16. Inability to comply with study and/or follow-up procedures.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Doxorubicin
Doxorubicin 60 mg/m2
• Cyclophosphamide
Cyclophosphamide 600 mg/m2
• Ixabepilone (Ixempra)
Ixabepilone 40 mg/m2
• Paclitaxel (Taxol)
Paclitaxel 80 mg/m2

Locations

Country	Name	City	State
Puerto Rico	San Juan Hospital	San Juan
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Emory/Winship Cancer Institute	Atlanta	Georgia
United States	Piedmont Healthcare	Atlanta	Georgia
United States	Augusta Oncology Associates	Augusta	Georgia
United States	Medical College of Georgia Cancer Specialists	Augusta	Georgia
United States	Medical Oncology Associates of Augusta	Augusta	Georgia
United States	Aventura Medical Center	Aventura	Florida
United States	Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Lynn Cancer Institute	Boca Raton	Florida
United States	Alamance Regional Medical Center	Burlington	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Associates in Hematology Oncology	Chattanooga	Tennessee
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	St. Louis Cancer Care	Chesterfield	Missouri
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Family Cancer Center	Collierville	Tennessee
United States	South Carolina Oncology Associates, PA	Columbia	South Carolina
United States	Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center	Columbus	Ohio
United States	Coastal Bend Cancer Center	Corpus Christi	Texas
United States	Florida Cancer Care	Davie	Florida
United States	St. Clare's Hospital Oncology and Hematology	Denville	New Jersey
United States	Fairview Medical Oncology Clinic	Edina	Minnesota
United States	Hematology/Oncology Inc	Elyria	Ohio
United States	Oncology Hematology Associates of SW Indiana	Evansville	Indiana
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Holy Cross Hospital	Ft. Lauderdale	Florida
United States	Center for Cancer and Blood Disorders	Ft. Worth	Texas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Memorial Regional Cancer Center	Hollywood	Florida
United States	Medical Oncology Methodist Hospital	Houston	Texas
United States	Cancer Center of Huntsville	Huntsville	Alabama
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	Hematology Oncology of Indiana	Indianapolis	Indiana
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	Northeast Arkansas Clinic	Jonesboro	Arkansas
United States	Research Medical Center	Kansas City	Missouri
United States	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida
United States	Wilshire Oncology Medical Group	LaVerne	California
United States	Suburban Hem Onc	Lawrenceville	Georgia
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	University of Southern Alabama	Mobile	Alabama
United States	Hematology Oncology Associates of Northern NJ	Morristown	New Jersey
United States	Lowcountry Hematology Oncology	Mt. Pleasant	South Carolina
United States	Coastal Cancer Center	Myrtle Beach	South Carolina
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Mid-Illinois Hematology & Oncology	Normal	Illinois
United States	Eastern Connecticut Hematology Oncology	Norwich	Connecticut
United States	Methodist Cancer Center	Omaha	Nebraska
United States	Kansas City Cancer Centers	Overland Park	Kansas
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	New Hope Cancer and Research Institute	Pomona	California
United States	Mercy Hospital	Portland	Maine
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Bux-Mont Oncology, Fox Chase Cancer Center	Rockledge	Pennsylvania
United States	South Texas Oncology and Hematology	San Antonio	Texas
United States	Hematology Oncology of the North Shore	Skokie	Illinois
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	St. John's Clinic	Springfield	Missouri
United States	Hickman Cancer Center (Flower Hospital)	Sylvania	Ohio
United States	Providence Medical Group	Terre Haute	Indiana
United States	Space Coast Medical Associates	Titusville	Florida
United States	Cotton O'Neil Cancer Center	Topeka	Kansas
United States	Southern Oncology and Hematology	Vineland	New Jersey
United States	Fallon Clinic	Worchester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival	Disease-free survival (DFS) defined as the time between randomization and the date of first documented disease recurrence, or death from any cause.	5.25 years	No
Secondary	Overall Survival	Overall survival is defined as the time between randomization to date of death from any cause.	5.25 years	No
Secondary	Number of treatment-emergent adverse events as a measure of safety.	The number of treatment-related adverse events will be graded using the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v. 3.0.	evry 21 days for duration of treatment	Yes