Partial Tumor Irradiation and Immunotherapy for Unresectable Lung Cancer

Summary

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. The 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. The 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. Once 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.

Eligibility

Inclusion Criteria:

1. Written informed consent
2. Biopsy proven unresectable lung adenocarcinoma
3. Ineligibility for surgery and conventional curative (whole tumor) radiotherapy, and relapsed/refractory to any previous standard of care therapy including ICI
4. Age ≥ 18 years,
5. 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,
6. Patient is willing and able to comply with the follow up including scheduled visits and examinations,
7. Adequate immune blood profile (not being immunodepressed): Leucocyte count ≥4000, Neutrophils count ≥1000.
8. PDL-1 ≥ 1%

Exclusion Criteria:

1. Patients with resectable/curable lung cancer
2. Tumors suitable for the standard of care therapies including surgery or conventional curative (whole tumor) radio-chemotherapy
3. Lung cancer histology other than adenocarcinoma
4. 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
5. 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)
6. Patients with uncontrolled seizures.
7. Inadequate immune blood profile (being potentially immunodepressed): Leucocyte count \<4000, Neutrophils count \<1000.
8. PDL-1 \< 1%

Conditions5

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