A Phase II study of weekly paclitaxel with or without LCL161 in patients with breast cancer
- Conditions
- Women with triple negative breast cancer whose tumors are positive fora defined pattern of gene expressionMedDRA version: 14.1Level: LLTClassification code 10006204Term: Breast carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-000677-23-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 100
1. Adult female (=18 years old)
2. Histologically confirmed diagnosis of invasive breast cancer, previously untreated (patients who have been treated for cancer of the contralateral breast can be included if there is at least a 2 year interval from last systemic treatment for breast cancer before randomization for this study). Disease must be negative immunohistochemically for estrogen and progesterone receptors (=1% of nuclei positive by IHC) and must not have
Her2 overexpression (by Herceptest or validated IHC assay; 0-1+ staining) or in cases of ambiguous Her2 expression (2+ staining), Her2 amplification (by CISH or FISH).
3. Positive for the LCL161 predictive gene expression profile as determined during molecular pre-screening
4. Candidates for mastectomy or breast-conserving surgery
5. Primary tumor of greater than 20 mm and less than 50 mm diameter measured by imaging (American Joint Committee on Cancer (AJCC) TNM stage T2)
6. Regional lymph node AJCC TNM stages N0-N2:
a. N0: No regional lymph node metastases
b. N1: Metastases to movable ipsilateral axillary lymph nodes
c. N2: Metastases in ipsilateral axillary nodes that are fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of axillary node metastases (Clinically apparent is defined as detected by clinical examination, grossly visible disease pathologically, or imaging studies (excluding lymphoscintigraphy))
7. Absence of distant metastatic disease (AJCC TNM stage M0)
8. ECOG performance status 0-1 (refer to Table 7-2)
9. Adequate bone marrow function defined as WBC =3.5 x 109/L, ANC WNL, platelets =LLN, and hemoglobin =10 g/dL
10. Adequate liver function defined as total serum bilirubin =1.5X ULN and serum transaminases =2.5X ULN
11. Adequate renal function defined as creatinine =1.5X ULN
12. Able and willing to give informed consent and comply with the protocol
13. Written informed consent obtained prior to any Screening/baseline procedures
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
1. Multicentric invasive tumors (defined as additional foci of tumor outside the breast quadrant containing the primary tumor); bilateral or inflammatory breast cancer (bilateral
mammography is required during Screening/baseline); locally recurrent breast cancer
2. Patients currently receiving systemic therapy for any other malignancy, or having received
systemic therapy for a malignancy in the preceding 3 months
3. Any concurrent severe and/or uncontrolled medical conditions that could increase the patient’s risk for toxicity while in the study or that could confound discrimination between
disease- and study treatment-related toxicities
4. Uncontrolled cardiac disease including:
a. History or presence of ventricular tachyarrhythmia
b. Unstable atrial fibrillation (ventricular response =100 bpm). Patients with stable atrial
fibrillation are eligible provided they do not meet any of the other cardiac exclusion criteria
c. Clinically significant resting bradycardia (HR =50 bpm)
d. Angina pectoris or acute myocardial infarction = 3 months prior to starting study drug
e. Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
5. Patients who are currently receiving chronic treatment with corticosteroids at a dose = 10 mg of prednisone (or its glucocorticoid equivalent) per day (inhaled and topical steroids
are allowed), or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug
6. Impaired GI function that may affect the absorption of LCL161
7. Patients who are currently receiving treatment with agents that are metabolized solely through CYP3A4/5 and have a narrow therapeutic index or are strong CYP2C8 inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are
CYP3A substrates (refer to Appendix 3). Caution should be used in patients taking other CYP2C8- or CYP3A4/5-interacting agents.
8. Prior hypersensitivity reactions to a taxane or to Cremophor EL (polyoxyethylated castor oil)
9. Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive ß-
HCG laboratory test (> 5 mIU/mL)
10. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 90 days after study treatment. Highly effective contraception methods include:
Total abstinence or
• Male partner or female sterilization or
• Combination of any two of the following (a+b or a+c, or b+c):
a. Use of oral, injected or implanted hormonal methods of contraception
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
c. Barrier methods of contraception: condom for male partner or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer that are positive for the gene expression signature.;Secondary Objective: 1. To characterize the safety and tolerability of the LCL161/paclitaxel<br>combination compared to weekly paclitaxel alone.<br>2. To assess other indicators of disease response for the LCL161 +<br>Paclitaxel combination compared to paclitaxel alone.<br>3. To evaluate whether combination treatment with LCL161 and paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone.<br>4. To evaluate the PK of LCL161 when given in combination with paclitaxel.;Primary end point(s): Pathological complete response (pCR) rate in breast after 12 weeks of<br>therapy in the control and experimental arms;Timepoint(s) of evaluation of this end point: 12 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Frequency of adverse events, serious adverse events and clinical laboratory abnormalities<br>2.<br>- pCR rate in breast, regional nodes and axilla<br>- rates of breast conserving surgery and mastectomy<br>- clinical response<br>- disease response using RECIST 1.1 criteria<br>3. Caspase 3 activation in tumor by IHC<br>4. PK parameters including but not limited to Cmax, Tmax, and AUC last;Timepoint(s) of evaluation of this end point: 1. 16 weeks<br>2. 12 weeks<br>3. 12 weeks<br>4. 12 weeks