HER2-positive Newly Diagnosed, Primary Breast Cancer Clinical Trial
— NeoPHOEBEOfficial title:
NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer
| Verified date | October 2019 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This randomized, parallel cohort, two stage, double-blind, placebo-controlled study evaluated the oral PI3K inhibitor BKM120 in combination with trastuzumab and paclitaxel in HER2-positive, PIK3CA wild-type and PIK3CA mutant primary breast cancer prior to surgery (neo-adjuvant setting).
| Status | Completed |
| Enrollment | 50 |
| Est. completion date | February 18, 2015 |
| Est. primary completion date | February 18, 2015 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Patient had provided a signed study ICF prior to any screening procedure - Patient was a female = 18 years of age - Patient has an ECOG performance status of 0-1 - Patient has a unilateral (multifocal or multicentric disease allowed), histologically confirmed, newly diagnosed early breast cancer >2cm by clinical examination and/or >1.5 cm confirmed by ultrasound or by MRI - Patient has tumor tissue available for central review of ER, HER2 and PI3K status with centrally confirmed HER2-positive disease and known PI3KCA mutation status - Patient has adequate bone marrow, renal and liver function - Patient is able to swallow and retain oral medication Exclusion Criteria: - Patient has received prior systemic treatment for currently diagnosed disease - Patient has a known contraindications, hypersensitivity or intolerance to trastuzumab, paclitaxel or products containing cremophor - Patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer - LVEF below 50% as determined by MUGA scan or ECHO - Patient has active cardiac disease or a history of cardiac abnormalities as defined in the protocol - Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 - Patient is currently receiving warfarin or other coumarin derived anti-coagulants - Patient is currently receiving chronic treatment with corticosteroids or another immunosuppressive agents (standard premedication for paclitaxel and local applications allowed) - Patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of CYP3A - Patient has certain scores on an anxiety and depression mood questionnaires - Pregnant or nursing (lactating) women or patients not willing to apply apply highly effective contraception as defined in the protocol |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Novartis Investigative Site | Parkville | Victoria |
| Australia | Novartis Investigative Site | Parkville | Victoria |
| Austria | Novartis Investigative Site | Salzburg | |
| Germany | Novartis Investigative Site | Lubeck | |
| Germany | Novartis Investigative Site | Offenbach | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Sevilla | Andalucia |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals | Breast International Group, German Breast Group, SOLTI Breast Cancer Research Group |
Australia, Austria, Germany, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants | Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR. | After 6 weeks | |
| Primary | Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT) | Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR. | After 6 weeks | |
| Primary | Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT) | Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR. | After 6 weeks | |
| Secondary | Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants | Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. | After week 6 | |
| Secondary | Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants | Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. | After week 6 | |
| Secondary | Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants | Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. | After week 6 | |
| Secondary | Rate of Breast Conserving Surgery (Most Radical Surgery) | Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS) | 18 weeks | |
| Secondary | Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition | Rate of pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]). If patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to NSABP guidelines. | After Week 6 | |
| Secondary | Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition | Rate of pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If a patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. | After Week 6 | |
| Secondary | Overall Objective Response Rate (ORR) Prior to Surgery for All Participants | Number of Overall objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered. | prior to surgery | |
| Secondary | Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) | pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions. | After Week 6 | |
| Secondary | Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-) | pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions. | After Week 6 | |
| Secondary | Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) | Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered. | After Week 6 | |
| Secondary | Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-) | Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered. | After Week 6 | |
| Secondary | Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis) | This included participants at definitive surgery irrespective of lymph node status | 18 weeks | |
| Secondary | Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0) | Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'. | 18 weeks |