Ignite Creation Date:
2026-03-26 @ 3:17 PM
Ignite Modification Date:
2026-03-30 @ 8:43 PM
Study NCT ID:
NCT07423169
Status:
RECRUITING
Last Update Posted:
2026-02-20
First Post:
2026-02-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Partial Tumor Irradiation and Immunotherapy for Unresectable Lung Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000077192', 'term': 'Adenocarcinoma of Lung'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 10}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2026-02-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2028-02', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-18', 'studyFirstSubmitDate': '2026-02-02', 'studyFirstSubmitQcDate': '2026-02-18', 'lastUpdatePostDateStruct': {'date': '2026-02-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-20', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-02', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '∆Progression-Free Survival (PFS) rate (PFS-2 vs PFS-1)', 'timeFrame': 'From radiotherapy treatment to the end of follow up period at 12 months', 'description': '∆Progression-Free Survival (PFS) rate measured as a time-difference (in months) between the survival free from tumor progression at local and distant site of initial ICI treatment (PFS-1) and rechallenge PTI-ICI (PFS-2).'}], 'secondaryOutcomes': [{'measure': 'Overall survival', 'timeFrame': 'From radiotherapy treatment until the date of death from any cause assessed up to 12 months', 'description': 'Calculated as the time (in months) from treatment initiation to death.'}, {'measure': 'Toxicity: presence of any treatment-related adverse events/side effects', 'timeFrame': 'From radiotherapy treatment initiation to the end of follow up period at 12 months', 'description': 'Number of Participants With Treatment-Related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0'}, {'measure': 'Validation of the anti-cancer immunity by the absolute counts of peripheral blood mononuclear cells (PBMC)', 'timeFrame': 'From radiotherapy treatment to the end of follow up period at 12 months', 'description': 'Measures the absolute counts of peripheral blood mononuclear cells (PBMC)'}, {'measure': 'Validation of the anti-cancer immunity by the absolute counts of surface marker expression', 'timeFrame': 'From radiotherapy treatment to the end of follow up period at 12 months', 'description': 'Measures the absolute counts of surface marker expression (CD markers) of the CD4+ T Cells, CD8+ T Cells, CD19+ B Cells, CD14+ Monocytes'}, {'measure': 'Validation of the anti-cancer immunity by the concentration (pg/mL or IU/mL) of immunoregulatory cytokines', 'timeFrame': 'From radiotherapy treatment to the end of follow up period at 12 months', 'description': 'Measures the concentration (pg/mL or IU/mL) of Interleukin-2 (IL-2) and Interferon-gamma (IFNg)'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Partial Irradiation', 'Immunomodulation', 'Radio-Vaccine'], 'conditions': ['Lung Adenocarcinoma', 'Bulky Tumors', 'Unresectable Cancer']}, 'descriptionModule': {'briefSummary': 'The present study will explore a novel treatment strategy for unresectable lung adenocarcinoma combining a unique unconventional radiotherapy technique for high dose partial tumor irradiation (PTI) sparing the peritumoral immune microenvironment (PIM) with an immune checkpoint inhibitor (ICI)-based immunotherapy. The present study will focus on patients with larger, unresectable bulky lung tumors who previously failed standard of care therapy, or are unsuitable for conventional radio-chemotherapy due to tumor size and volume, and do not have any further therapeutic option left. This concept implies that a very high, ablative radiation dose (typically 20-25Gy per fraction) is delivered exclusively to the central bulky-tumor segment sparing at the same time surrounding PIM and therefore preserving its function.\n\nThe present study will explore the potential clinical advantages of the above described innovative treatment concept as a rechallenge treatment: following the disease progression during initiated first-line ICI-therapy, or following discontinuation of ICI-therapy, a same previously used agent (ICI) will be added the PTI to boost its immunologic anti-tumor effects. The treatment response will be measured by comparing the progression-free survival 1 (PFS-1) (ICI-therapy alone) and progression-free survival 2 (PFS-2) (combined rechallange PTI-ICI) rates.\n\nThe primary endpoint will be ∆PFS rate (PFS-2 vs PFS-1) assessed according to the modified iRECIST criteria. Secondary endpoints will include overall survival, toxicity, and exploration and validation of the anti-cancer immunity.\n\nOnce treatment is completed, follow up will be performed on a regular basis (at 6 and 12 weeks, and every 3 months later on) by CT, MRT or PET-CT imaging to allow for endpoints assessment, or at any time in case of suspected disease progression. Patients will also be followed clinically with history and physical examinations, vital signs, and laboratory examinations as indicated.', 'detailedDescription': 'The present study will explore a novel treatment strategy for unresectable lung adenocarcinoma combining a unique unconventional radiotherapy technique for high dose partial tumor irradiation (PTI) sparing the peritumoral immune microenvironment (PIM) with an immune checkpoint inhibitor (ICI)-based immunotherapy. The present study will focus on patients with larger, unresectable bulky lung tumors who previously failed standard of care therapy, or are unsuitable for conventional radio-chemotherapy due to tumor size and volume, and do not have any further therapeutic option left. The present novel, combined approach will be offered as an alternative to a palliative or best supportive care. In previous studies PTI has shown to be effective, safe and capable of inducing significant immunomodulatory and neoadjuvant effects in complex unresectable resistant bulky tumors, lung cancer including. PTI was previously explored alone, therefore so far never combined with any kind of systemic therapy, in order first to assess its own efficiency when immunomodulation and tumor control is concerned. Its combination with immunotherapy is very attractive due to its high immunostimulative potential as shown in previous studies. Aditionally, it has been shown that the PD-L1 level is widely upregulated after radiotherapy, on not only tumor cells, but also macrophages, myeloid-derived suppressor cells, and derived exosomes, which correlate to improved effectiveness of immunotherapy resulting in better therapeutic outcomes. Taking all together into account, it is expected from the PTI-ICI combination to generate more powerful immunomodulatory anti-tumor effect compared to the conventional radiotherapy combination with immunotherapy leading to improved tumor control and prognosis. One of the reasons for this is the PTI´s sparring effect of PIM, which otherwise is irradiated with a full dose of radiation when conventional radiotherapy is used and therefore destroyed, which is why the same conventional radiotherapy is quite immunosuppressive and is not expected to work optimally when combined with immunotherapy. In order to improve the radiotherapy therapeutic ratio by the highly complex unresectable tumors left without other therapeutic options, PTI was purposefully designed to add to the radiation-mediated tumor cell killing component, an additional component of radiation-induced immune-mediated tumor cell killing, a concept known as the "radiation-vaccine". This concept implies that a very high, ablative radiation dose (typically 20-25Gy per fraction) is delivered exclusively to the central bulky-tumor segment sparing at the same time surrounding PIM and therefore preserving its function. PTI is going to be delivered as a single fraction (1 day) in order to release the tumor antigens and pro-inflammatory cytokines from destroyed tumor cells which could then sensitize loco-regional (previously spared) immune cells surrounding the tumor, resulting in an immune anti-tumor response, like a true vaccine.\n\nFor the purpose of PTI-treatment planning, the targeted central tumor segment, or so-called BTV (Bystander Tumor Volume), will be delineated using the combination of 18F-FDG-PET-CT (PET-CT; not mandatory, if performed by patient for the purpose of the staging) and contrast-enhanced CT (mandatory). In case there is no PET-CT available at time of treatment planning the BTV will simply be contoured as the Gross Tumor Volume (GTV) minus 5-10mm. This margin will depend on the proximity of the nearby organs at risk (OAR) (excluding main bronchus or heart). PTI will be delivered with photons by means of stereotactic body radiotherapy (SBRT) technique. Based on tumor location, its volume and risk factors related to nearby critical structures, radiation dose might be reduced to 15Gy/fraction, according to patient´s individual risk factors, respectively. Regarding the ICI, an anti-PD-L1 antibody will be administered at three-week intervals until progression.\n\nThe present study will explore the potential clinical advantages of the above described innovative treatment concept as a rechallenge treatment: following the disease progression during initiated first-line ICI-therapy, or following discontinuation of ICI-therapy, a same previously used agent (ICI) will be added the PTI to boost its immunologic anti-tumor effects. The treatment response will be measured by comparing the progression-free survival 1 (PFS-1) (ICI-therapy alone) and progression-free survival 2 (PFS-2) (combined rechallange PTI-ICI) rates.\n\nThe analysis of the bio-molecular mechanisms potentially responsible for the observed clinical effects of the PTI-ICI treatment in terms of radiation-induced anti-tumor immune response will also be performed. This will include the anti-tumor immunity as profiling of peripheral blood mononuclear cells (PBMC) following the PTI-ICI therapy through translational immune studies on blood specimens. Two key cytokines that are involved in modulation of immune response, Interleukin-2 (IL-2) and Interferon Gamma (INFg), will serially be assessed, at baseline, after radiotherapy treatment, before each administration of the ICI in order to determine their potential role in immunomodulation by PTI-ICI.\n\nThis is a pilot study in which the investigators will enroll up to 10 patients with locally advanced or metastatic unresectable lung adenocarcinoma to assess the feasibility and potential effectiveness of a novel approach.\n\nThe hypothesis implies that for an effective immune modulation leading to improved therapeutic ratio, the entire tumor volume may not need to be irradiated but only a partial tumor volume sparing the PIM, in order to overcome the tumor tolerance initiating the immune cycle in radiation-spared PIM, resulting in tumoricidal radio-immune anti-tumor effects.\n\nThe primary endpoint will be ∆PFS rate (PFS-2 vs PFS-1) assessed according to the modified iRECIST criteria. Secondary endpoints will include overall survival, toxicity, and exploration and validation of the anti-cancer immunity.\n\nOnce treatment is completed, follow up will be performed on a regular basis (at 6 and 12 weeks, and every 3 months later on) by CT, MRT or PET-CT imaging to allow for endpoints assessment, or at any time in case of suspected disease progression. Patients will also be followed clinically with history and physical examinations, vital signs, and laboratory examinations as indicated.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Written informed consent\n2. Biopsy proven unresectable lung adenocarcinoma\n3. Ineligibility for surgery and conventional curative (whole tumor) radiotherapy, and relapsed/refractory to any previous standard of care therapy including ICI\n4. Age ≥ 18 years,\n5. Female patients must either be of non-reproductive potential (i.e. post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) OR women of fertile age must have adequate conception prevention measures and must have a negative serum pregnancy test upon study entry,\n6. Patient is willing and able to comply with the follow up including scheduled visits and examinations,\n7. Adequate immune blood profile (not being immunodepressed): Leucocyte count ≥4000, Neutrophils count ≥1000.\n8. PDL-1 ≥ 1%\n\nExclusion Criteria:\n\n1. Patients with resectable/curable lung cancer\n2. Tumors suitable for the standard of care therapies including surgery or conventional curative (whole tumor) radio-chemotherapy\n3. Lung cancer histology other than adenocarcinoma\n4. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control\n5. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, (1)\n6. Patients with uncontrolled seizures.\n7. Inadequate immune blood profile (being potentially immunodepressed): Leucocyte count \\<4000, Neutrophils count \\<1000.\n8. PDL-1 \\< 1%'}, 'identificationModule': {'nctId': 'NCT07423169', 'briefTitle': 'Partial Tumor Irradiation and Immunotherapy for Unresectable Lung Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Karl Landsteiner University of Health Sciences'}, 'officialTitle': 'Rechallenge Using Combined Partial Tumor Irradiation and Immune Checkpoint Inhibitor-based Immunotherapy for Unresectable Lung Adenocarcinoma: a Pilot Study', 'orgStudyIdInfo': {'id': 'GS3-EK-4/995-2025'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Unresectable, bulky lung adenocarcinoma', 'description': 'The present study will explore a novel treatment strategy for unresectable lung adenocarcinoma combining a unique unconventional radiotherapy technique for high dose partial tumor irradiation (PTI) sparing the peritumoral immune microenvironment (PIM) with an immune checkpoint inhibitor (ICI)-based immunotherapy. The present study will focus on patients with larger, unresectable bulky lung tumors who previously failed standard of care therapy, or are unsuitable for conventional radio-chemotherapy due to tumor size and volume, and do not have any further therapeutic option left. The present novel, combined approach will be offered as an alternative to a palliative or best supportive care. This concept implies that a very high, ablative radiation dose (typically 20-25Gy per fraction) is delivered exclusively to the central bulky-tumor segment sparing at the same time surrounding PIM and therefore preserving its function. PTI is going to be delivered as a single fraction (1 day).', 'interventionNames': ['Radiation: Partial Tumor Irradiation']}], 'interventions': [{'name': 'Partial Tumor Irradiation', 'type': 'RADIATION', 'description': 'A very high, ablative radiation dose of 20-25Gy will be delivered exclusively to the central bulky-tumor segment sparing at the same time surrounding Peritumoral Immune Microenvironment and therefore preserving its function. Partial Tumor Irradiation is going to be delivered as a single fraction (1 day-treatment).', 'armGroupLabels': ['Unresectable, bulky lung adenocarcinoma']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3500', 'city': 'Krems', 'state': 'Austria', 'status': 'RECRUITING', 'country': 'Austria', 'contacts': [{'name': 'Slavisa Tubin, MD', 'role': 'CONTACT', 'email': 'slavisa.tubin@krems.lknoe.at', 'phone': '+43 02732 90040'}, {'name': 'Slavisa Tubin, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Peter Errhalt, Prim. Clin. Ass. Prof.', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Radiation Oncology Department', 'geoPoint': {'lat': 48.40921, 'lon': 15.61415}}], 'centralContacts': [{'name': 'Slavisa Tubin, MD', 'role': 'CONTACT', 'email': 'slavisa.tubin@krems.lknoe.at', 'phone': '+43 02732 90040'}], 'overallOfficials': [{'name': 'Slavisa Tubin, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Clinic Krems, Radiation Oncology Department'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'ICF'], 'ipdSharing': 'YES', 'description': 'Demographics, Patient- and Tumor-features'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Karl Landsteiner University of Health Sciences', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}