The purpose of the study is to determine whether treatment with alpelisib in combination with olaparib can delay the time to cancer progression compared to standard-of-care chemotherapy in participants with your type of ovarian cancer known as…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Radiological tumor assessments by a Blinded Independent Review Committee (BIRC)
per RECIST 1.1 will be performed and used for the primary analysis of PFS:
1. At screening within 28 days prior to Cycle 1 Day 1.
2. Imaging assessments for response evaluation will be performed every 8 weeks
(±7 days) after randomization during the first 18 months and every 12 weeks (±7
days) thereafter
Additionally, tumor assessments will be used for a supplemental analysis where
PFS will be defined by one of the following:
1. Radiological tumor progression as assessed by investigator (RECIST 1.1);
2. Identification of new lesions or unequivocal progression of existing lesions
by additional diagnostic tests (e.g. histology/cytology, ultrasound, endoscopy
or any other imaging technique) AND CA-125 progression according to the
Gynecologic Cancer Intergroup (GCIG)
3. Definitive clinical signs and symptoms of disease progression ([i]
intractable cancer-related pain, [ii] malignant bowel obstruction/worsening
dysfunction, or [iii] unequivocal symptomatic worsening of ascites or pleural
effusion) AND CA-125 progression according to GCIG criteria.
Disease progression will not be diagnosed based on CA-125 progression in the
absence of at least 1 of the criteria defined above.
Secondary outcome
Pharmacokinetic profile of alpelisib+olaparib.
Safety assessments (physical exam, ECOG status, body weight, vital signs, lab
assessments, pregnancy testing, ECG(s), cardiac imaging, AE-severity,
relationship with the study drug, seriousness).
Biormarker assessments and patient reported outcomes.
Background summary
Alpelisib belongs to a group of medicines called phosphatidylinositol 3-kinases
(PI3K) inhibitors. Alpelisib blocks the activity of a biological pathway called
the PI3K pathway. PI3K pathway activation depends on changes of multiple
molecules. In particular, the changes of PIK3CA (a gene coding for the PI3K
protein) or a molecule called PTEN (phosphatase and tensing homolog) are
responsible for keeping the PI3K pathway active all the time. This continuous
PI3K pathway activation is thought to contribute to the onset and growth of
tumours. Therefore, alpelisib has been designed to stop these types of cells
from multiplying, which might help to reduce or delay tumour growth.
Olaparib (LynparzaTM) is a PARP (poly [adenosine diphosphate-ribose]
polymerase) inhibitor, this means that olaparib stops an enzyme found in the
body known as PARP from working. In our cells when DNA is damaged, PARP and the
genes involved in the Homologous Recombination Repair (HRR) mechanism (such as
the BRCA1 and BRCA2 genes) help to repair the broken strand of DNA. Olaparib
aims to block the repair of DNA which can cause cancer cells to die. Previous
studies have shown that olaparib significantly reduces the risk of progression
in patients with recurrent ovarian cancer.
The combinatino of alpelisip and olaparib will be compared in this study to
paclitaxel or PLD. PLD stands for pegylated liposomal doxorubicine. Paclitaxel
or PLD are forms of chemotherapy, and are registered in the Netherlands. Both
drugs will be administered through an IV directly into a vein. Paclitaxel every
week and PLD once every 4 weeks.
Study objective
The purpose of the study is to determine whether treatment with alpelisib in
combination with olaparib can delay the time to cancer progression compared to
standard-of-care chemotherapy in participants with your type of ovarian cancer
known as platinum resistant/refractory high-grade serous/ endometrioid ovarian
cancer with no BRCA mutation.
Study design
A phase III study with multiple treatment arms, randomized in a 1:1 ratio
between the combination therapy of olaparib+alpelisib and a chemotherapy of
choice (paclitaxel or PLD).
Intervention
Participants are devided into 2 groups:
Group 1: Participants will receive tablets of alpelisib once a day and olaparib
twice a day
Group 2: Participants will receive chemotherapy, with either paclitaxel
(infusion each week) or PLD (infusion once every 4 weeks). The choice of drug
belongs to the investigator.
Study burden and risks
The risks and side-effects associated with the treatments (olaparib+alpelisib
or chemotherapy), aside from those the risks assocaited with the assessments in
the study (bloddraw(s) imaging etc).
Burden:
Cycles of 4 weeks:
Cycle 1: 3-4 visits, depending on the group
Cycle 2: 3-4 visits, dpending on the group
Cycle 3 and on: 1-3 vistis depending on the group.
Duration of visits: usually 1-2 hours unless there is a course of blooddraws
for pharmacokinetic assessment, depening on the given treatment such a visit
can take between 2 and 5 hours.
During study visits other assessments are also performed, frequency and number
of these assessments are dependent on the treatment and can include: physical
exam, blooddraw(s), ECG(s), imaging studies, pregnancy testing and if necessary
a tumor biopsy.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
Participant has histologically confirmed diagnosis of high-grade serous or
high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary
peritoneal cancer.
Measurable disease, i.e., at least one measurable lesion per RECIST 1.1
criteria (a lesion at a previously irradiated site may only be counted as a
target lesion if there is clear sign of progression since the irradiation).
If no measurable disease is present, the disease should be assessable by
Gynecologic Cancer Intergroup criteria (GCIC) for CA-125.
Participant has no germline BRCA1/2 mutation as determined by an FDA-approved
assay.
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1.
Participant has received prior bevacizumab or is not eligible to receive
bevacizumab due to medical reasons as per investigator*s discretion
Participant has platinum-resistant (progression within one to six months after
completing platinum-based therapy) or platinum refractory disease (progression
during treatment or within 4 weeks after the last dose), where platinum-based
therapy is not an option, according to the GCIG 5th Ovarian Cancer Consensus
Conference definitions (Wilson et al 2016). The platinum-based chemotherapy
regimen does not necessarily need to be the last regimen the participant
received prior to study entry.
Participant must have received at least one but no more than three prior
systemic treatment regimens and for whom single-agent chemotherapy is
appropriate as the next line of treatment.
Participant has adequate bone marrow and organ function.
Exclusion criteria
Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor.
Participant is concurrently using other anti-cancer therapy.
Participant is in a state of small or large bowel obstruction or has other
impairment of gastrointestinal (GI) function or GI disease.
Participant has had surgery within 14 days prior to starting study drug or has
not recovered from major side effects.
Participant has not recovered from all toxicities related to prior anticancer
therapies to baseline or NCI CTCAE Version 4.03 Grade <=1. Exception to this
criterion: participants with any grade of alopecia are allowed to enter the
study.
Participants with liver impairment and Child Pugh score B or C
Participant has received radiotherapy <= 4 weeks or limited field radiation for
palliation <= 2 weeks prior to randomization, and who has not recovered to
baseline, grade 1 or better from related side effects of such therapy (with the
exception of alopecia).
Participant has a known hypersensitivity to any of the study drugs or
excipients.
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 | EUCTR2019-004682-40-NL |
| ClinicalTrials.gov | NCT04729387 |
| CCMO | NL77468.056.21 |