Combining SBRT and pembrolizumab in early stage non-small cell lungcancer patients planned for surgery: exploring safety and immunological proof of principle.
- Conditions
- lungcancerNon-small cell lung carcinoma10038666
- Registration Number
- NL-OMON49358
- Lead Sponsor
- Vrije Universiteit Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
Histologically or cytologically confirmed diagnosis of early stage (T1cN0,
T2aN0 and T2bN0 ) peripherally located NSCLC, eligible for surgical resection.
Highly suspected NSCLC is defined as an a priori change of >85% that the
lesion is malignant, according to the publication of Herder et al. (59)
Be willing and able to provide written informed consent/assent for the trial.
Be 18 years of age or older on day of signing imformed consent.
Have measurable disease based on RECIST 1.1.
Must provide tissue from a core or excisional biopsy of the primary tumor
lesion.
Have a performance status of 0-1 on the ECOG Performance Scale.
Demonstrate adequate organ function as defined in Table 1, all screening labs
should be performed within 10 days of treatment initiation.
Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study
medication. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
Female subjects of childbearing potential should be willing to use two methods
of birth control or be surgically sterile, or abstain from heterosexual
activity for the course of the study through 120 days after the last dose of
study medication. Subjects of childbearing potential are those who have not
been surgically sterilized or have not ben free form menses for >1 year.
Male subjects should agree to use an adequate method of contraception starting
with the first dose of study therapy through 120 days after the last dose of
study therapy.
Is currently participating in or has participated in a study of an
investigational agent or using investigational device within 4 weeks of the
first dose of treatment.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or
any other form of immunosuppressive therapy within 7 days proor to the first
dose of trial treatment.
Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who
has not recovered (i.e. grade 1 or lower, or at baseling) from adverse events
due to agents administered more than 4 weeks earlier.
Has had prior chemotherapy, targeted small molecule therapy, or radiation
therapy within 2 weeks prior to study day 1 or who has not recovered (i.e.
grade 1 or lower at baseline) from adverse events due to a previously
administered agent.
Has a known additional malignancy that is progressing or requires active
treatment. Exceptions include basal cell carcinoma of the skin, squamous cel
carcinoma of the skin, or in situ cervical cancer that has undergone
potentially curative therapy.
Has an active autoimmune disease requiring systemic treatment within the past 3
months or a documented histroy of clinically severe autoimmune disease, or a
syndrome that requires systemic steroids or immunosuppressive agents. Subjects
with vitiligo or resolved childhood asthma/atopy would be an exception to this
rule. Subjects that require intermittent use of bronchodilators or local
steroid injections would not be excluded from the study. Subjects with
hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be
excluded from the study.
Has a history of (non-infectious) pneumonitis that required steroids, evidence
of interstitial lung disease or active, non-infectious pneumonitis.
Has an active infection requiring systemic therapy.
Has a histroy or current evidence of any condition ,therapy or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the
bst interest of the subject to participate, in the opinion of the treating
investigator.
Has known psychiatric or substance abude disorders that would interfere with
cooperation with the requirements of the trial.
Is pregnant or breastfeedig, or expecting to conceive or father children within
the projected duration of the trial, starting with the pre-screening or
screening visit through 120 days after the last dose of trial treatment.
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)
antibody (including ipilimumab or any other antibody or drug specifically
targeting T-cell co-stimulation or checkpoint pathways).
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA
[qualitative] is detected).
Has received a live vaccine within 30 days prior to the first dose of trial
treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Examination of tumor core biopsies and resection material. FACS analysis on<br /><br>EBUS-FNA of tumor draining lymphnodes (TDLNs) and peripheral blood to detect<br /><br>immunomodulation.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The correlations of in-vivo PD-1 expression, quantified by immune-PET, with<br /><br>tissue and blood based immune-parameters.<br /><br>Assessment of clinical signs of radiation pneumonitis</p><br>