To evaluate the efficacy, safety, pharmacology, and patient-reported outcomes of the combination of taselisib plus fulvestrant compared to placebo plus fulvestrant in ER+, HER2- postmenopausal women with locally advanced or MBC and who have had…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare the efficacy between taselisib + fulvestrant versus placebo +
fulvestrant as measured by investigator-assessed PFS in patients with
PIK3CA-mutant tumors
Secondary outcome
- To compare the overall objective response rate (ORR) 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 +
fulvestrant as measured by OS in patients with PIK3CA-mutant tumors
- To estimate the duration of objective response (DOR) within taselisib +
fulvestrant versus placebo + fulvestrant in patients with PIK3CA-mutant tumors,
on the basis of tumor assessments made by the investigator
- 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 +
fulvestrant as measured by PFS determined by blinded independent central review
(BICR) in patients with PIK3CA-mutant tumors
Background summary
Not all ER+ breast cancers respond optimally to endocrine therapy.
Hyperactivation of the PI3K/AKT/mTOR signaling pathway was proven to promote
both de novo and acquired resistence to hormone therapy. This supports the
hypothesis that blocking PI3K/AKT/mTOR pathway signaling may have a therapeutic
benefit in patients with Er+, HER2-negative breast cancer.
Study objective
To evaluate the efficacy, safety, pharmacology, and patient-reported outcomes
of the combination of taselisib plus fulvestrant compared to placebo plus
fulvestrant in ER+, HER2- postmenopausal women with locally advanced or MBC
and who have had recurrence or progression of diasesa on or after
administration of an aromatase-inhibitor therapy.
Study design
Phase III, double-blinded, randomized, placebo-controlled study of taselisib
plus fulvestrant versus placebo plus fulvestant
Intervention
One group receives taselisib, 4 mg tablet once daily plus fulvestrant im every
28 days.
The other group receives placebo tablet, once daily plus fulvestrant im every
28 days.
Study burden and risks
3 questionnaires (QLQ-32. QLQ-C30, EQ-5D)
Patient diary
Physical examination every cycle
Fasting before a number of blood draws
Most common adverse events: diahrrea, nausea, hyperglycemia, fatigue,
stomatitis, decreased appetite, rash and vomitting.
Randomisation risk: the treatment that the patient receives may prove to be
less effective or to have more side effects than the other study treatment
Possible risks and discomfort associated with drawing blood: May cause pain
where the needle is inserted, and there is a small risk of bruising or
infection at the place where the needle is inserted. Some people experience
dizziness, upset stomach or fainting when their blood is drawn.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
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
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003185-25-NL |
| ClinicalTrials.gov | NCT02340221 |
| CCMO | NL51145.056.14 |