The main objective is to evaluate the percentage of patients that do not experience progression during the first 18 weeks of treatment with Atezolizumab in patients affected by advanced solid tumors.The secondary objectives are to evaluate the…
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Source
Brief title
Condition
- Other condition
Synonym
Health condition
gevorderde solide tumoren
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy objective for this study is as follows:
1. To evaluate non-progression rate (NPR) at 18 weeks in patients with advanced
solid tumors treated with Atezolizumab, defined as the
percentage of patients with complete response (CR) partial response (PR) or
stable disease (SD) as assessed by the Investigator according to
Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST, v1.1) or
according to disease specific criteriat for prostate cancer and malignant
pleural mesothelioma
Secondary outcome
EFFICACY OBJECTIVES
The secondary efficacy objectives for this study are as follows:
1. Efficacy: To evaluate NPR at 24 weeks, overall response rate (ORR), best
overall response (BOR), clinical benefit rate (CBR), duration of
response (DOR), time to tumor progression (TTP) and progression-free survival
(PFS), as assessed by the Investigator using RECIST v1.1 and
modified RECIST (latter also NPR at 18 weeks) or by disease-specific criteria
for prostate cancer and malignant pleural mesothelioma.
Overall survival (OS).
2. Safety: incidence, nature, and severity of adverse events, incidence of
anti-atezolizumab antibodies, mean dose and number of cycles of
atezolizumab
3. Pharmacokinetics: maximum and minimum serum atezolizumab concentrations
SAFETY OBJECTIVES
The safety objectives for this study are as follows:
1. To evaluate the safety and tolerability of Atezolizumab in patients with
advanced solid tumors
2. To characterize the immunogenic potential of Atezolizumab by measuring anti
Atezolizumab antibodies and to explore the potential relationship of the
immunogenicity response with safety and efficacy
PHARMACOKINETIC OBJECTIVES
The PK objectives for this study are as follows:
1. To characterize the pharmacokinetics of Atezolizumab
EXPLORATORY OBJECTIVES
The exploratory objectives for this study are as follows:
1. To evaluate the relationship between tumor tissue PD-L1 expression and
measures of efficacy, including NPR at 18 weeks and 24 weeks, ORR, BOR, CBR,
DOR, TTP, PFS and OS.
2.To assess predictive and prognostic exploratory biomarkers in archival and/or
fresh tumor tissue and plasma and their association with disease status and/or
response to study treatment *
3. To evaluate exploratory pharmacodynamic (PD) biomarkers (e.g., T, B and NK
cell enumeration, T cell subpopulations like CD8+ T, effector/memory T cells,
regulatory T cells, changes in expression of CD25 or human leukocyte antigen-DR
[HLA-DR],
interferon [IFN]-gamma production,IL-2 and other exploratory biomarkers) in
tumor tissue and plasma and their association with disease status, and/or
response to study treatment, tumor immunobiology or tumor type
Background summary
Atezolizumab is a human Ig G1 monoclonal antibody consisting of two heavy
chains (448 amino acids) and two light chains (214 amino acids) and is produced
in Chinese hamster ovary cells. Atezolizumab was engineered to eliminate
Fc-effector function via a single amino acid substitution at position 298 on
the heavy chain, which results in a non-glycosylated antibody that has minimal
binding to Fc receptors and prevents Fc-effector function at expected
concentrations in humans. Atezolizumab targets human PD-L1 and inhibits its
interaction with its receptors,PD-1 and B7.1 (CD80, B7-1). Both of these
interactions are reported to provide inhibitory signals to T cells.
Atezolizumab is being investigated as a potential therapy against solid tumors
and hematologic malignancies in humans.
Study objective
The main objective is to evaluate the percentage of patients that do not
experience progression during the first 18 weeks of treatment with Atezolizumab
in patients affected by advanced solid tumors.
The secondary objectives are to evaluate the percentage of patients that do not
progress during the first 24 weeks of treatment with Atezolizumab,
the percentage of patients that achieve a response, the best response achieved,
the duration of response and the progression free survival;
these variables will be evaluated according to RECIST criteria v1.1. and
according to modified RECIST criteria. Moreover OS will be evaluated as
secondary endpoint.
Study design
This will be an open-label, multicenter, multinational, multicohort, phase II
study. For each cohort, the study will consist of a Screening Period (Day *35
to *1), a Treatment Period, a Treatment Discontinuation Visit occurring * 30
days after the last dose of study medication and a 24-month Survival Follow-up
Period (Figure 1).
Intervention
Atezolizumab IV (fixed dose of 1200 mg) will be administered on Day 1 of 21-day
cycles. The initial dose will be delivered over 60 minutes. If the first
infusion is well-tolerated, the second and all subsequent infusions may be
delivered over 30 minutes. During the initial treatment stage, Atezolizumab
treatment may be continued as long as patients are experiencing clinical
benefit as assessed by the investigator, i.e., in the absence of unacceptable
toxicity or symptomatic deterioration attributed to disease progression after
an integrated assessment of radiographic data, biopsy results (if available),
and clinical status.
Study burden and risks
For more information, please see the answer on question number E9.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
1.Histologically documented advanced (i.e. stages III or IV) solid timors that
meet protocol defined cohort specifications, with progressive disease at study
entry and at least one line of prior line systemic anticancer therapy or for
which there is no alternative therapy known to prolong survival , Measurable
disease as defined by RECIST, v1.1. (except for prostate cancer and malignant
pleural mesothelioma) and disease-specific criteria for patients with prostate
cancer (see Appendix 6) and malignant pleural mesothelioma (see Appendix 7), 3.
Estern Cooperative Oncology group (ECOG) Performance Status of 0 or 1, 4.
Adequate hematologic and end organ function, defined by labortory results
obtained within 3 days prior to the first study treatment., 5.Women who are not
postmenopausal (* 12 months of non-therapy-induced amenorrhea) or surgically
sterile must have a negative serum pregnancy test result within 14 days prior
to initiation of study drug
Exclusion criteria
1. Malignancies other than disease under study within 5 years prior to Cycle 1
Day 1, with the exception of those with a negligible risk of metastasis or
death treated with expected curative outcome, 2 .History of treated
asymptomatic or symptomatic CNS metastasis or presence of CNS metastases as
determined by CT or MRI evaluation during screening and prior radiographic
assessments, 3 .Leptomeningeal disease, 4. Any approved anticancer therapy,
including chemotherapy, hormonal therapy or radiotherapy, within 3 weeks prior
to initiation of study treatment; with certain exception
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 | EUCTR2015-000269-30-NL |
| CCMO | NL52894.031.15 |
| Other | Wordt geregistreerd op www.clinicaltrials.gov |