Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor.
- Conditions
- -C50 Malignant neoplasm of breastMalignant neoplasm of breastC50
- Registration Number
- PER-001-13
- Lead Sponsor
- OVARTIS BIOSCIENSES PERU S.A.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Sex
- Female
- Target Recruitment
- 2
1. Patient is an adult, female ≥ 18 years old at the time of informed consent
2. Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
3. Patient has archival tumor tissue for the analysis of PI3K-related biomarkers (PIK3CA mutation, PTEN mutation, PTEN expression). One tumor block (preferred) or a minimum of 20 unstained slides is recommended to determine the PI3K activation status. Enrollment in the study will be contingent to the central laboratory confirming reception of adequate amount of tissue
4. Patient has inoperable locally advanced or metastatic breast cancer
5. Patient has HER2 negative breast cancer (based on most recently analyzed biopsy) defined as a negative immunohistochemistry, fluorescent, non-florescent chromogenic or silver in situ hybridization (respectively FISH/CISH/SISH) test or an IHC status of 0, 1+ or 2+ (if IHC 2+, a negative SISH/FISH/CISH test is required) by local laboratory testing
6. Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
7. Patient is postmenopausal. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
8. Patient has disease refractory to AI defined as:
• Recurrence while on, or within 12 months of end of adjuvant treatment with AI, or
• Progression while on, or within one month of end of AI treatment for locally advanced or MBC
Note: AI do not have to be the last treatment prior to enrollment in the run-in treatment phase. Patients who received maximum one prior chemotherapy line for MBC are allowed. Other prior anticancer therapies, e.g. tamoxifen are also allowed. Patients do not need to meet the definition of refractory to AI” within any specified time period prior to enrollment in the run-in treatment phase. Patients can receive any number of endocrine/hormonal lines of therapy before or after meeting the definition of refractory to AI”
9. Patient is able to swallow and retain oral medication
10. Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment in the run-in treatment phase.
11. Patient must have as per RECIST 1.1 (Appendix 7):
• measurable disease
or
• non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
Note: Measurable lesions include lytic or mixed (lytic + blastic) bone lesions, with an identifiable soft tissue component that meets the measurability criteria per RECIST 1.1. Patients with only non-measurable lesions (e.g. pleural effusion, ascites) and no lytic or a mix of lytic and blastic bone lesions are not eligible.
12. Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
• Platelets (plt) ≥ 100 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dl
• INR
1. Patient has received previous treatment with PI3K inhibitors, AKT inhibitors, mTORi or fulvestrant
2. Patient has received more than one chemotherapy line for metastatic disease
• A chemotherapy line in advanced disease is an anticancer regimen(s) that contains at least 1 cytotoxic chemotherapy agent and was discontinued due to progression. If a cytotoxic chemotherapy regimen was discontinued for a reason other than disease progression then this regimen does not count as a prior line of chemotherapy
• Adjuvant/neo-adjuvant therapy will be counted as prior line of chemotherapy for metastatic/recurrent disease if the patient had a progression/recurrence while or within 6 months after completion of the therapy (12 months for taxane-based therapy)
3. Patient has a known hypersensitivity to any of the excipients of BKM120 or fulvestrant
4. Patient has symptomatic CNS metastases
• Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the entry in the run-in treatment phase (including radiotherapy and/or surgery)
5. Patient has a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated, basal or squamous cell carcinoma, nonmelanomatous skin cancer or curatively resected cervical cancer).
6. Patient who has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia, bone marrow and organ functions)
7. Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
8. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
9. Patient is currently receiving increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent, as chronic administration of corticosteroids (> 5 days) can induce CYP3A4
• The following uses of corticosteroids are permitted: single doses; topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
10. Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
11. Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the run-in treatment phase is initiated. Switching to a different medication prior to entry in the run-in treatment phase is allowed. Please refer to the Table 14-1 in Appendix 2 for a list of strong and moderate inhibitors and inducers of CYP3A4
12. Patient has a score ≥ 12 on the PHQ-9 questionnaire
13. Patient selects a response of 1, 2 or 3” to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)
14. Patient has a GAD-7 mood scale score ≥ 15
15. Patient has a medically documented hi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method