A phase III trials program exploring the integration of Bevacizumab, Everolimus (RAD001), and Lapatinib into current neoadjuvant chemotherapy regimes for primary breast cancer - GeparQuinto
- Conditions
- breast cancer, primary systemic therapyTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2006-005834-19-DE
- Lead Sponsor
- GBG Forschungs GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 2727
1. Written informed consent for all study procedures including an additional core biopsy after the first four cycles of EC +/-B must be obtained and documented according to local regulatory requirements prior to beginning specific protocol procedures.
2. Patient has consented to the biomaterial collection and the paraffin-embedded tumor tissue block of diagnostic core has been sent to central biomaterial banks.
3. Complete baseline documentation must be sent to GBG Forschungs GmbH.
4. Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
5. Tumor lesion in the breast with a palpable size of ? 2 cm or a sonographical size of ? 1 cm in maximum diameter. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion.
6. Patients should be in a stage of disease in which adjuvant chemotherapy would be considered. Therefore the following tumor stages are eligible *:
- locally advanced tumors with cT3 or cT4 or
- Estrogen (ER) and progesterone (PgR) receptor negative tumors or
- ER or PgR positive tumors which are cN+ (for cT2) or pNSLN+ (for cT1).
* During the Run-In Phase only patients with cT4 or cT3 cN+ disease are eligible.
In patients with multifocal or multicentric breast cancer, the largest lesion should be measured.
7. Known HER-2/neu status detected on core biopsy. HER-2/neu positive is defined as HercepTest IHC 3+ or FISH+.
8. Age ? 18 years.
9. Karnofsky Performance status index ? 80%.
10. Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution and above 55%.
11. Laboratory requirements:
a) Hematology
- Absolute neutrophil count (ANC) ? 2.0 x 109 / L and
- Platelets ? 100 x 109 / L and
- Hemoglobin ? 10 g/dL (? 6.2 mmol/L)
b) Hepatic function
- Total bilirubin < 1x UNL and
- ASAT (SGOT) and ALAT (SGPT) ? 2.5x UNL and
- Alkaline phosphatase ? 5x UNL.
Patients with ASAT and / or ALAT > 1.5x UNL and associated with alkaline phosphatase > 2.5x UNL are not eligible for the study.
c) Renal function
Creatinine ? 175 µmol/L (2 mg/dL) < 1.5x UNL
(or the calculated creatinine clearance should be ? 30 mL/min).
d) Proteinuria
Urine dipstick for proteinuria < 2+. Patients discovered to have = 2+ proteinuria on dipstick urinalysis should undergo a 24-hour urine collection and must demonstrate
= 1 g of protein in 24 hours.
12. Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential.
13. Complete staging work-up within 3 months prior to randomization. All patients must have bilateral mammography, breast ultrasound (? 21 days), breast MRI (optional), chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan done. In case of positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated.
14. Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or at a cooperating center.
Are the trial subjects unde
1. Patients with low or moderate risk, who are only doubtful candidates for adjuvant chemotherapy and do not fulfil the inclusion criterion No. 5.
2. Evidence of distant metastasis.
3. Prior chemotherapy for any malignancy.
4. Prior radiation therapy for breast cancer.
5. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
6. Inadequate general condition (not fit for anthracycline-taxane based chemotherapy).
7. Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
8. Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >160 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
9. Previous thromboembolic event (except pregnancy-related thromboembolic events without genetic disposition).
10. Known hemorrhagic diathesis or coagulopathy with increased bleeding risk.
11. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
12. Pre-existing motor or sensory neuropathy of a severity ? grade 2 by NCI criteria.
13. Currently active infection.
14. Active peptic ulcer, incomplete wound healing or unhealed bone fracture.
15. Disease significantly affecting gastrointestinal function, e.g. malabsorption syndrome, resection of the stomach or small bowel, ulcerative colitis.
16. History of abdominal fistula or any grade 4 non-gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment.
17. Severe pulmonary condition / illness.
18. Unstable diabetes mellitus; Insulin-dependent type II diabetes mellitus.
19. Major surgery within the last 28 days or anticipation of the need for major surgery during study treatment with bevacizumab. No minor surgeries including insertion of an indwelling catheter within 24 h prior to chemotherapy.
20. Definite contraindications for the use of corticosteroids.
21. Known hypersensitivity reaction to one of the investigational compounds or incorporated substances; or known dihydropyrimidine dehydrogenase deficiency.
22. Concurrent treatment with:
a) oral chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (? 10 mg methylprednisolone or equivalent).
b) oral contraception and hormone replacement therapy. Prior treatment must be stopped before study entry.
c) virostatic agents like sorivudine or analogs like brivudine, concurrent treatment with aminoglycosides.
d) anticoagulants: heparin, warfarin as well as acetylic acid (e.g. Aspirin®) at a dose of > 325 mg/day or clopidogrel at a dose of > 75 mg/day.
e) other experimental drugs or any other anti-cancer therapy.
f) drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A, e.g. Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazole, Ritonavir, Telithromycin, Erythromycin, Verapamil, Diltiazem (see appendix 6) within the las
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