To assess the efficacy of atezolizumab in combination with carboplatin in metastatic ILC
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients who remain free of progression at 6 months. Progression
as defined by RECIST 1.1 will be used.
Secondary outcome
* Proportion of patients free of progression (RECIST 1.1 at 6 months in the
IR-profile subgroup vs the non-IR-subgroup as defined by gene expression
profiling
* Proportion of patients who remain free of progression at 12 months.
Progression as defined by RECIST 1.1 will be used.
* Progression as defined by iRECIST
* Overall survival
* Percentage of patients with toxicity (according to CTCAE v4.03) and
immune-related toxicity defined as the Adverse Events of Special Interest
(AESI's) for atezolizumab
* Objective response rate (RECIST 1.1)
Background summary
Immunotherapy by anti-PD1 or anti-PDL1 has resulted in a true breakthrough in
oncology. However, in hormone-receptor (ER) positive breast cancer patients
with metastatic disease, the response rate is relatively small (5-12%). But
because this treatment is capable of inducing long-term remissions and there is
also a "clinical unmet need" for these patients as all patients eventually die,
follow-up research is very important. However, two aspects are crucial: 1)
selecting patients that really benefit from anti-PDL1, thus researching
predictive biomarkers, and 2) strategies to explore how to combine anti-PDL1
with other treatments. Preclinical research performed in the NKI-AVL can help
with this. Work by Rene Bernards, Sabine Linn and Lodewyk Wessels has shown
that there is a subgroup of lobular breast tumors, where possibly a great deal
of interaction exists between the cancer cell and the immune system. In
addition, Karin de Visser's laboratory discovered that lobular breast tumors
respond well to anti-PDL1 when combined with platinum-containing chemotherapy.
In the GELATO study we want to study these two facets further by treating
patients with metastatic lobular breast cancer with anti-PDL1 in combination
with platinum. Due to the detailed characterization of the tumors and immune
system of those patients benefiting from this treatment, we contribute to the
improvement of immunotherapy for patients with metastatic lobular breast
cancer.
Study objective
To assess the efficacy of atezolizumab in combination with carboplatin in
metastatic ILC
Study design
This is a single arm multicenter non-randomized phase II trial testing the
efficacy of the combination of carboplatin plus atezolizumab in metastatic ILC
Intervention
Carboplatin AUC 1.5 , intravenous administration, weekly schedule, maximum 12
administrations (no steroids necessary).
After two administrations of carboplatin, atezolizumab (1200 mg flat dose) will
be given in a 3-weekly schedule until tumor progression.
After 12 months of atezolizumab treatment discontinuation is allowed in case of
ongoing response or stable disease. At signs of progression after
discontinuation of the treatment, atezolizumab can be re-started. Carboplatin
will be given for 12 weeks. If carboplatin has to be discontinued due to
toxicity, atezolizumab can be continued as monotherapy.
Study burden and risks
Patients are at risk for development of carboplatin and atezolizumab relates
side effects and pain and risk of bleeding due to the tumor biopsies
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Age
Inclusion criteria
* Signed and written informed consent
* Age 18 year or older
* Metastatic or incurable locally advanced lobular breast cancer with confirmation of the lobular histology and E-cadherin loss or aberrant staining (IHC) on a biopsy of a metastatic lesion.
* Estrogen receptor expression of at least 10% on a metastatic lesion (independent of progesterone receptor expression and HER2 expression)
* Metastatic lesion accessible for histological biopsies
* Evidence of progression of disease
* A maximum of two lines of palliative chemotherapy. Carboplatin pretreatment is allowed, as long as no progression was observed and the last dose was administered 6 months before starting study treatment
* WHO performance status of 0 or 1
* Evaluable disease or measurable according to RECIST 1.1
Exclusion criteria
* Leptomeningeal disease localization
* History of having received other anticancer therapies within 2 weeks of start of the study drug
* History of immunodeficiency, autoimmune disease, conditions requiring immunosuppression
* Prior treatment with immune checkpoint blockade
* Live vaccine within 2 weeks prior to start of study
* Active other cancer
* Active hepatitis B
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 | EUCTR2017-001428-23-NL |
| ClinicalTrials.gov | NCT03147040 |
| CCMO | NL61567.031.17 |