Immune Profiling of Stage III Non-small Cell Lung Cancer Patients Treated With Concurrent Chemoradiation and Adjuvant Durvalumab: A Prospective Observational Phase II Trial

Carcinoma, Non-Small-Cell Lung Clinical Trial

— IPON-1  

Official title:

Immune Profiling of Stage III Non-small Cell Lung Cancer Patients Treated With Concurrent Chemoradiation and Adjuvant Durvalumab: A Prospective Observational Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04432142
• Other study ID #: IPON-1
• Status: Recruiting
• Start date: April 1, 2021
• Est. completion date: April 1, 2024

Study information

• Verified date: August 2023
• Source: Maastricht Radiation Oncology
• Contact: Chantal Overhof
• Phone: +31 88 44 55 686
• Email: chantal.overhof[@]maastro.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC (non-small cell lung cancer) patients. Identifying the effect of the treatment on immune cells and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers. Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers. This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.

Description:

Even with the addition of durvalumab to concurrent chemoradiation, approximately only half of the patients are alive at 3 years, and more have progressed already, either locally or distant. Not much is known regarding to identification of patients that will benefit from adjuvant durvalumab, or regarding resistance to adjuvant durvalumab after chemoradiation. Most data on immunotherapy resistance come from metastatic patients treated with monotherapy PD-(L)1 antagonists. Depending on PD-L1 expression level, 10-44% of patients respond well to PD-(L)1 antagonists. The majority of patients are either unresponsive, or experience a tumor recurrence after achieving an initial response. The development of individual immunological treatment strategies (e.g. selection of best treatment: mono- or combination ICI, ICI combined with chemotherapy, or the addition of radiotherapy) is hampered by the lack of knowledge in the best timing, sequencing, and dosing of all modalities and the lack of optimal biomarkers for monitoring the treatment response. This highlights the need of clear biomarkers that can be used to select the best treatment for each individual patient and predict whether patients will benefit from adjuvant immunotherapy. Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC patients. Identifying the effect of the treatment on immune cells (e.g. T-, B-, NK-cells, dendritic cells, macrophages) and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers. Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers. This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathological diagnosis of adequately staged (according to standard practice using chest-CT, FDG-PET, brain imaging MRI/CT) NSCLC
• Participant is willing and able to give informed consent for participation in the trial
• Male or female, aged 18 years or above
• Scheduled to receive one of the following two therapeutic strategies:
• Concurrent chemotherapy and radiotherapy with photons (60 Gy in 30 fractions of 2 Gy) in patients with stage III NSCLC
• Concurrent chemotherapy and radiotherapy with protons (60 Gy in 30 fractions of 2 Gy) in patients with stage III NSCLC
• Is able and willing to comply with all trial requirement

Exclusion Criteria:

• Mixed non-small cell lung cancer with other histologies such as small cell lung cancer
• Not able to comply with the study protocol
• Less than 18 years' old
• Pregnancy or not able to comply with adequate contraception in women with child baring potential
• Previous radiotherapy to the chest for benign or malignant conditions, including radiation for breast cancer
• Previous malignancy treated with chemotherapy, immune therapy or radiotherapy (irrespective of when this happened)
• Previous malignancies treated with surgery only are allowed if 2 years or more before inclusion in the present study

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Locations

Country	Name	City	State
Netherlands	Maastricht Radiation Oncology (MAASTRO clinic)	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immune changes	Number of patients with immune changes in stage III NSCLC patients receiving concurrent chemoradiation with protons or photons followed by durvalumab.	3 months
Secondary	PFS	Progression Free Survival	12 months
Secondary	OS	Overall survival	12 months
Secondary	Toxicity chemoradition	- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 during and after concurrent chemoradiation, also in relation to the irradiated bone marrow volume	until 3 months after chemo/radiotherapy
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 during courses of Durvalumab	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 of durvalumab and chemoradiation treatment	Until 12 months after chemo/radiotherapy
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Incidence and severity of adverse events (Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 and patient reported outcome (PRO)-CTCAE)	Until 12 months after chemoradiation
Secondary	Immune changes compared	Number of patients with immune changes that are distinct for proton therapy compared with photon therapy	Until 12 months after chemoradiation
Secondary	Cardiac function	Troponins	Until 12 months after chemoradiation
Secondary	Cardiac function	ECG QT Interval	Until 12 months after chemoradiation
Secondary	Cardiac function	blood pressure	Until 12 months after chemoradiation
Secondary	Cardiac function	BNP	Until 12 months after chemoradiation
Secondary	Neurocognitive function test	MOS	Until 12 months after chemoradiation
Secondary	Neurocognitive function test	Controlled oral word association	Until 12 months after chemoradiation
Secondary	Neurocognitive function test	Trail making test	Until 12 months after chemoradiation
Secondary	Neurocognitive function test	HVALT-R test	Until 12 months after chemoradiation
Secondary	Tumor material	Obtaining tumor material from standard diagnostic material for translational purposes	Until 12 months after chemoradiation