lung cancer lung carcinoma
Conditions
Interventions
89Zr-durva-PET procedure: The PET tracer used will be 89Zr-durvalumab
(89Zr-MEDI4736). 89Zr-durva-PET procedures will be performed at baseline
(tracer injection 1-2 weeks prior to start of cCRT), 1
for the pts participating undergoing the
optional scans this is a total of 7x7cc per PET procedure (at week 0 and at
week 1) and 4x7cc during the last PET procedure
biopsy: optionally, a lymph node
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Have a histologically or cytologically confirmed diagnosis of thoracic disease stage III NSCLC and planned to receive concurrent chemotherapy and radiotherapy on the thorax. * Patients with oligometastatic stage IV comprising a thoracic stage III and up to 2 distant metastases amenable for radical local consolidative therapy are also eligible. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. * Age > 18 years at time of study entry. * Have a World Health Organisation (WHO) performance status of 0 or 1. * Life expectancy of > 3 months. * Have measurable disease based on RECIST 1.1. * Must consent to allow use of PD-L1 measurements obtained from tumor biopsies. * Adequate organ and bone marrow function, as deemed acceptable by the treating physician in the context of cCRT. * Females of childbearing potential must use reliable methods of contraception from the time of screening until 3 months after discontinuing study treatment. Acceptable methods of contraception include total sexual abstinence, tubal ligation, hormonal contraceptives that are not prone to drug-drug interactions, copper-banded intra-uterine devices and vasectomised partner. All methods of contraception must be used in combination with the use of a condom by their male sexual partners for intercourse. * Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion criteria
Exclusion criteria: * Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study. * Participation in another clinical study with an investigational product during the last 4 weeks. * Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) * 30 days prior to the first dose of study drug If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator. * Any unresolved toxicity NCI CTCAE Grade *2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. * Patients with Grade *2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. * Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. * Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Limited surgical excision of isolated lesions for palliative or diagnostic reasons is acceptable. * History of allogenic organ transplantation. * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Patients without active disease in the last year may be included but only after consultation with the study physician e. Patients with celiac disease controlled by diet alone. * Active infection as judged to be unacceptable by the treating physician in the context of cCRT. * History of active primary immunodeficiency. * Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Assessments: 89Zr-MEDI4736 will be administered using microdosing, i.e. patients will be injected with 22.5 mg of MEDI4736 on 3 time points. Any toxicity suspected to be associated with MEDI4736 will be reported in the presentation of safety data. All toxicities associated with chemotherapy and radiotherapy will not be listed. Efficacy Assessments: This is an exploratory imaging study of 89Zr-labeled MEDI4736 and therefore the primary endpoint of this study is to assess 89Zr-MEDI4736 uptake in tumor lesions at 3 different time points. The effect cCRT on 89Zr-MEDI4736 uptake in tumor lesions, in malignant and non-malignant lymph nodes, and in the spleen will be quantified. The efficacy of MEDI4736 will not be assessed. Pharmacodynamic Assessments The imaging data will be correlated to tumor PD-L1 expression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Venous blood samples will be used for PK analysis. (Ir)reversible uptake of 89Zr-durvalumab (89Zr-MEDI4736) in normal organs and tumorous lesions will be modelled according Patlak analysis. | — |
Countries
Netherlands
Outcome results
None listed