Primary: To compare PFS between ribociclib plus fulvestrant to fulvestrant monotherapy (plus placebo) among men and postmenopausal women with HR+, HER2-negative advanced breast cancer who received no or only one prior endocrine treatment for…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PFS.
Secondary outcome
Overall survival, centrally assessed PFS, overall response rate, time to
response, duration of response, clinical benefit rate, performance status,
adverse events, global health status/quality of life, pharmacokinetics.
Background summary
Treatment of hormone receptor (HR) positive, HER2-negative breast cancer still
represents an unmet medical need as a significant number of patients are
expected to have, or to develop, resistance to endocrine therapies that have
been given in the adjuvant or first line metastatic setting. CDK4/6 pathway
alterations appear to play a key role in the development of this resistance.
The rationale for assessing the efficacy of ribociclib, a CDK4/6 inhibitor, in
combination with the hormonal agent fulvestrant, is therefore based upon the
role of the CDK4/6 pathway in HR+ breast cancer and the potential synergy when
combined with hormonal agents such as fulvestrant.
The purpose of this study is to determine whether treatment with ribociclib
plus fulvestrant will result in an improved progression free survival (PFS)
compared to fulvestrant and placebo in men and in postmenopausal women with
HR+, HER2-negative advanced breast cancer who have received no or only one
prior endocrine treatment for advanced disease.
Study objective
Primary: To compare PFS between ribociclib plus fulvestrant to fulvestrant
monotherapy (plus placebo) among men and postmenopausal women with HR+,
HER2-negative advanced breast cancer who received no or only one prior
endocrine treatment for advanced disease.
Secondary:
Overall survival, centrally assessed PFS, overall response rate, time to
response, duration of response, clinical benefit rate, performance status,
adverse events, global health status/quality of life, pharmacokinetics.
Study design
Randomized, double-blind phase III trial. Treatment cycles of 4 weeks.
Randomization (2:1) to
• fulvestrant IM 500 mg (day 1 of each cycle) + ribociclib capsules 600 mg OD
(days 1 to 21)
• fulvestrant IM 500 mg (day 1 of each cycle) + placebo.
Stratification by lung or liver metastases and previous endocrine therapy.
4 week screening phase, treatment phase until disease progression or
unacceptable toxicity and follow-up for survival.
Approx. 660 patients.
Intervention
Treatment with fulvestrant with or without ribociclib.
Study burden and risks
Risk: Adverse effects of fulvestrant with or without ribociclib.
Burden: Cycles of 4 weeks. Cycle 1 and 2: 2 visits, from cycle 3 onwards 1
visit. Visit duration 2-4 hours.
2 IM injections of 5 mL with fulvestrant every 4 weeks (plus 2 extra injections
on cycle 1, day 15)
Physical examination: once per cycle.
Blood draws (fasting, 10-20 ml/occasion): once per cycle (exception: cycle 2
twice).
ECG: every cycle up to cycle 6 (4 times 2-3 ERCGs at different time points).
Echocardiogram/MUGA-scan during screening.
2 tumor biopsies (1 may be archival sample, the other is optional).
CT-/MRI-scan: every 8 weeks during first 18 months and every 12 weeks
thereafter. Skin photographs in case of skin lesions.
Questionnaires QLQ-C30, EQ-5D-5L , BPI-SF (pain): every 8 weeks during first 18
months and every 12 weeks thereafter.
Optional storage and use of the remaining blood and tissue for future research.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
• Men or postmenopausal females (18 years and above).
• HER2 negative, estrogen-receptor positive and/or progesterone receptor
positive breast cancer. (based on most recent analyzed biopsy)
• Measurable disease or at least one predominantly lytic bone lesion.
• Advanced disease (see protocol section 5.2 for details).
• ECOG performance status 0 or 1.
• Adequate bone marrow and organ function.
Exclusion criteria
• Symptomatic visceral disease.
• Prior treatment with chemotherapy (except for neoadjuvant or adjuvant
chemotherapy), fulvestrant or any CDK4/6 inhibitor.
• Child pugh score B or C.
• Clinically significant, uncontrolled heart disease and/or recent cardiac
events. See protocol section 5.3 for details.
• Radiotherapy <= 4 weeks or limited field radiation for palliation <= 2 weeks
prior to randomization.
• CNS involvement (exceptions: see protocol section 5.3).
• Use of any of the following substances that cannot be discontinued 7 days
prior to start of treatment: known strong inducers or inhibitors of CYP3A4/5,
drugs that have a known risk to prolong the QT interval or induce Torsades de
Pointes, drugs with narrow therapeutic window and are predominantly metabolized
through CYP3A4/5, herbal preparations/medications, dietary supplements.
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 |
|---|---|
| Other | clinicaltrials.gov; registratienummer NCT02422615 |
| EudraCT | EUCTR2015-000617-43-NL |
| CCMO | NL53067.028.15 |