A Multicenter Phase III Randomized Trial of Adjuvant Therapy for Patients with HER2-Positive Node-Positive or High Risk Node-Negative Breast Cancer Comparing Chemotherapy Plus Trastuzumab with Chemotherapy Plus Trastuzumab Plus Bevacizumab - BETH (CIRG 011 (TRIO)/NSABP B-44-I)
- Conditions
- Resected node-positive or high risk node-negative, invasive HER2-positive breast cancer.MedDRA version: 9.1Level: HLGTClassification code 10006291Term: Breast neoplasms malignant and unspecified (incl nipple)
- Registration Number
- EUCTR2007-005182-35-SK
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 3509
See Section 4 of protocol and Annex A for full details:
1. The patient must have consented to participate and must have signed and dated both EC-approved consent forms. The pre-entry central HER2 testing consent form must be signed before tumor material is sent to the central laboratory for HER2 testing
2. Patients must be female
3. The patient must be >=18 years old.
4. The patient must have an ECOG performance status of 0 or 1.
5. The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
6. The breast cancer must be HER2-positive based on test results as follows:
*Local testing (if available) should demonstrate that the tumor is IHC 2+ or 3+ or is considered to be HER2-positive for gene amplification by FISH, CISH, or other in situ hybridization method. (If local IHS test results are considered equivocal, the tumor can be submitted for central HER2 testing.)
*Central testing (a requirement for ALL patients) must demonstrate that the tumor is HER2-positive which is defined as IHC 3+ and/or FISH-positive.
7.Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed.
8.Patients must have undergone either a total mastectomy or lumpectomy.
9.The interval between the last surgery for breast cancer and randomization must be no more than 84 days and not less than 28 days.
10. For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist.
11. For patients who undergo mastectomy, margins must be free of gross residual tumor. Patients with microscopic positive margins are eligible.
12. All of the following staging criteria (according to the 6th edition of the AJCC Cancer Staging Manual) must be met:
* By pathologic evaluation, primary tumor must be pT1-3;
* By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b
* If pN0, must also meet at least one of the following criteria:
* Pathologic tumor size > 2.0 cm;
* ER negative and PgR negative;
* Histologic and/or nuclear grade 2 (intermediate) or 3 (high); or
* Age < 35 years
13. Patients must have completed one of the following procedures for evaluation of pathologic nodal status:
* Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if SN is positive;
* Sentinel lymphadenectomy alone if pathologic nodal staging based on sentinel lymphadenectomy is pN0, pN1mi or pN1b; or
* Axillary lymphadenectomy without SN isolation procedure.
14. Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, or PET scan), performed within 3 months prior to randomization, does not demonstrate metastatic disease and meets other testing parameters as described in Criterion 16 below.
15. Patients with alkaline phosphatase that is > ULN but <= 2.5 x ULN are eligible for inclusion in the study if a bone scan or PET scan, performed within 3 months prior to randomization, does not demonstrate metastatic disease.
16. The following organ specific criteria (according to the local laboratory facility) must be met to provide evidence of adequate organ function, at the time of study entry :
Bone Marrow Function (most recent postoperative test performed within 6 weeks prior to randomization)
*ANC must be >= 1200/mm3;
*Platelet count must be >= 100,000/
See Section 4 of protocol and Annex A for full details:
Disease-specific :
1. Inflammatory breast cancer.
2. Synchronous contralateral breast cancer (invasive or non-invasive).
Clinical Staging :
3. Definitive clinical or radiologic evidence of metastatic disease. (Chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 3 months prior to randomization.)
Cancer History :
4.History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral DCIS treated with excision and RT.
5. History of non-breast malignancies within the 5 years prior to study entry, except for the following: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
6. Previous therapy with anthracyclines, taxanes, carboplatin, trastuzumab, or bevacizumab for any malignancy.
7. Treatment including RT, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to randomization.
Endocrine Therapy :
8. Continued therapy with any hormonal agent such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor. (Patients are eligible if these medications are discontinued prior to randomization.)
Medical History :
9. Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to:
* Active cardiac disease :
** angina pectoris that requires the use of anti-anginal medication;
** ventricular arrhythmias except for benign premature ventricular contractions;
** supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
** conduction abnormality requiring a pacemaker;
** valvular disease with documented compromise in cardiac function; and
** symptomatic pericarditis.
* History of cardiac disease:
** myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function;
** history of documented CHF; and
** documented cardiomyopathy.
10. Uncontrolled hypertension defined as systolic BP > 150 mmHg or diastolic BP > 90 mmHg, with or without anti-hypertensive medication. (BP must be assessed within 28 days prior to randomization.) Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria.
11. History of hypertensive crisis or hypertensive encephalopathy.
12. History of TIA or CVA.
13. History of any arterial thrombotic event within 12 months before randomization.
14. Symptomatic peripheral vascular disease.
15. Intrinsic lung disease resulting in dyspnea.
16. Unstable diabetes mellitus.
17. Active infection or chronic infection requiring suppressive antibiotics.
18. Any significant bleeding within 6 months before randomization, exclusive of menorrhagia in premenopausal women.
19. Known bleeding diathesis or coagulopathy.
20. Requirement for therapeutic doses of coumadin or equivalent.
21. Gastroduodenal ulcer(s) documented by endoscopy to be active within 6 months of randomization.
22. History of GI perforation, abdominal fistulae, or intra-abdominal abscess.
23. Non-healing wound, skin ulcers, or incompletely healed bone fracture.
24. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy. (Note: Placement of a vascular access device is not
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method