E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
WOMEN WITH ER-POSITIVE AND HER2-NEGATIVE, LOCALLY ADVANCED OR METASTATIC BREAST CANCER WHO HAD DIDEASE RECURRENCE OR PROGRESSION DURING OR AFTER AROMATASE INHIBITOR THERAPY |
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E.1.1.1 | Medical condition in easily understood language |
Advanced or metastatic breast cancer that is positive for the estrogen receptor and negative for the HER2 receptor and has recurred or progressed on or after aromatase inhibitor therapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the efficacy between taselisib plus fulvestrant versus placebo plus fulvestrant as measured by investigator-assessed progression-free survival (PFS) in patients with PIK3CA mutant tumors |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are the following:
•To evaluate the safety of taselisib plus fulvestrant versus placebo plus fulvestrant.
•To compare the efficacy between taselisib plus fulvestrant versus placebo plus fulvestrant as measured by OS in patients with PIK3CA mutant tumors.
•To compare the overall objective response rate (ORR), and estimate the
duration of response (DOR) between taselisib plus fulvestrant versus
placebo plus fulvestrant in patients with PIK3CA mutant tumors, based
on investigator assessment.
•To compare the clinical benefit rate (CBR) between taselisib +
fulvestrant versus placebo + fulvestrant in patients with PIK3CA mutant
tumors, on the basis of tumor assessments made by the investigator
•To compare the efficacy between taselisib + fulvestrant versus placebo
+ fulvestran as measured by PFS determined by blinded independent
central review (BICR) in patients with PIK3CA mutant tumors |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Postmenopausal women with histologically or cytologically confirmed locally advanced or metastatic estrogen-receptor positive (ER+) breast cancer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Endocrine therapy (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study
- Radiologic/objective evidence of recurrence or progression to the most recent systemic therapy for breast cancer
- Recurrence or progression during or after aromatase inhibitor
- Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Consent to provide tumor tissue (block or a minimum of 20 slides) from the most recent tumor tissue for PIK3CA-mutation testing; a valid cobas PIK3CA mutation result by central testing is required
- Adequate hematologic and end-organ function within 28 days prior to treatment initiation
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E.4 | Principal exclusion criteria |
- HER2-positive disease by local laboratory testing (immunohistochemistry [IHC] 3+ staining or in situ hybridization positive)
- Prior treatment with fulvestrant
- Prior treatment with a PI3K inhibitor, mTOR inhibitor (e.g. everolimus), or AKT inhibitor
- Prior anti-cancer therapy within 2 weeks prior to Day 1 of Cycle 1
- Prior radiation therapy within 2 weeks prior to Day 1 of Cycle 1
- All acute treatment-related toxicity must have resolved to Grade </= 1 or be deemed stable by the Investigator
- Prior treatment with > 1 cytotoxic chemotherapy regimen for metastatic breast cancer
- Concurrent hormone replacement therapy
- Known untreated or active central nervous system (CNS) metastases
- Type 1 or Type 2 diabetes mellitus requiring anti-hyperglycemic medications
- History of inflammatory bowel disease or active bowel inflammation
- Clinically significant cardiac or pulmonary dysfunction
- Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus or C
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E.5 End points |
E.5.1 | Primary end point(s) |
Investigator-assessed Progression-free survival (PFS), as determined by the investigator with the use of RECIST version 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 3.5 years |
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E.5.2 | Secondary end point(s) |
1. Overall survival
2. Overall objective response (partial response [PR] plus complete
response [CR]), as determined by using RECIST v.1.1
3. Clinical benefit, defined as objective response (PR+CR), or no disease
progression lasting for at least 24 weeks since randomization
4. Duration of objective response
5. Incidence of adverse events, according to National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
6. BICR-assessed PFS, defined as the time from randomization to the
first occurrence of disease progression, as determined by the BICR with
the use of RECIST v1.1, or death from any cause (whichever occurs
earlier) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 to 6. Up to approximately 3.5 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 81 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Bulgaria |
Canada |
Colombia |
Czech Republic |
France |
Germany |
Greece |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Sweden |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will be considered completed when approximately 330 deaths in patients with PIK3CA mutant tumors have been reported and the final analysis of overall survival is completed or when the Sponsor decides to stop the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |