To assess the proportion of patients who are alive without disease progression at 6 months based on local investigator assessment per RECIST v1.1 in cohort A and cohort B 13-03-2019: new cohort added (3 cohorts now)
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
the proportion of patients who are alive without disease progression at 6
months based on local investigator assessment using RECIST v1.1 in each cohort
Secondary outcome
PFS based on local investigator assessment using RECIST v1.1 in each cohort
PFS2, ORR, CBR based on local investigator*s assessment according to RECIST
v1.1 in each cohort
Type, frequency and severity of adverse events per CTCAE v4.03
Type, frequency and severity of laboratory toxicities per CTCAE v4.03
Background summary
promising pre-clinical data showing potential for cell death in addition to
decreased proliferation have been observed when PI3K inhibitors are given in
combination with endocrine therapy
Preclinical and clinical studies of HR+ BC, alpelisib has shown synergistic
antitumor effects when used with endocrine therapy (e.g. letrozole). The
combination of letrozole and alpelisib was determined to be safe.
Up to 45% of HR+ BC present with a mutation in the PIK3CA gene, and thus these
tumors may be particularly suited to treatment with PI3K inhibitor alpelisib.
HR+ BC particularly if previously treated with endocrine agents - may display a
dependency on the PI3K pathway that is independent of a PIK3CA mutation and
hence confer a level of sensitivity to alpelisib in non-PIK3CA mutant BC tumors
as well.
With the approval of CDK 4/6 inhibitor combinations with endocrine therapy and
the clinical data adapting fulvestrant over an AI in the first line aBC, the
treatment landscape for HR+, HER2-negative aBC is rapidly changing to include
CDK 4/6 inhibitors in the first line and second line with an AI or fulvestrant.
Therefore, this study will assess the efficacy and safety of alpelisib
combination in PIK3CA mutant HR+, HER2-negative aBC patients following
progression on CDKi based regimen.
Study objective
To assess the proportion of patients who are alive without disease progression
at 6 months based on local investigator assessment per RECIST v1.1 in cohort A
and cohort B
13-03-2019: new cohort added (3 cohorts now)
Study design
a phase II, multicenter, open-label, three-cohort, non-comparative study of
alpelisib plus either fulvestrant or letrozole
4april2022: addition of an extension phase for the patients benefitting from
the treatment in the core study and for whom no PSDS is available.
Intervention
All participants will be treated with :
- alpelisib 300 mg once daily, orally
- either fulvestrant, 500 mg intra muscular, once every 28 days OR letrozol 2.5
mg once daily, orally
Study burden and risks
RISK: adverse events of treatment with PDR001 and Fulvestrant or letrozol
Burden: Cycles of 4 weeks, Cycle 1: 3 visits, cycle 2: 2 visits from cycle 3
onwards one visit
Physical examination: once per cycle.
Blooddraws : at least once per cycle
ECG: every 3 cycles
MUGA every 4 cycels
CT-/MRI-scan: during screening, cycle 4, every 8 weeks during first 6 months
and every 12 weeks thereafter.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. adult male or female >= 18 years old at the time of consent
2. Patient has PIK3CA mutation confirmed by a Novartis designated laboratory,
or
Patient has a pathology report confirming PIK3CA mutant status It is also
mandatory to
provide a tumor sample collected after the most recent
progression or recurrence
3. Patient has a confirmed, HER2-negative aBC.
4. Patient is a men, or pre or postmenopausal woman.
Postmenopausal as defined:
• Prior bilateral oophorectomy
• Age >=60
• Age <60 and amenorrhea for 12 or more months
Special requirements are required for premenopausal women.
5. Patient has a confirmed diagnosis of ER+ and/or PgR+ breast cancer , 6.
documented evidence of tumor progression
- cohort A and B : CDK 4/6 inhibitor treatment as last treatment regimen
- cohort C: AI treatment and received systemic chemotherapy or ET as last
treatment regimen , 7. Patients must have either:
Measurable disease, i.e., at least one measurable lesion as per RECIST v1.1
criteria
If no measurable disease is present, then at least one predominantly lytic bone
lesion must
be present
8. Patient has ECOG (Eastern Cooperative Oncology Group) Performance Status <= 2
9. Males or females with advanced breast cancer not amenable to curative
therapy.
Exclusion criteria
1. Patient has received prior treatment with any PI3K inhibitors
2. Patients with central nervous system (CNS) involvement unless they meet ALL
of the
following criteria:
• At least 4 weeks from prior therapy completion to starting the study treatment
• Clinically stable CNS tumor at the time of screening untreated or without
evidence of
progressions for at least 4 weeks after treatment
3. Patient with clinically manifest diabetes mellitus, or documented steroid
induced diabetes
mellitus
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 | EUCTR2016-004586-67-NL |
| ClinicalTrials.gov | NCT03056755 |
| CCMO | NL61664.068.17 |