Clinical trial NCT05647590: SBRT/RT in Oligometastatic Stage IV NSCLC
Official title: SBRT/RT to All Sites of Disease After Three Months of First-line Systemic Chemotherapy in Oligometastatic Stage IV NSCLC Before Maintenance
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non Small Cell Lung Cancer
Keywords: non small cell lung cancer
radiotherapy
stereotactic robotic radiotherapy
chemotherapy
CyberKnife
acceptable toxicity
Lead sponsor: University Hospital Ostrava
Sponsor class: OTHER
First posted: 2022-12-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The core hypothesis to be tested is that the use of consolidative SBRT followed by maintenance chemotherapy in patients with less than or equal to 10 metastatic sites will improve progression-free survival (PFS) with acceptable toxicity compared to maintenance chemotherapy alone.

Detailed description: Lung cancer is the main cause of death from cancer in the Czech Republic and in the world. Non-small cell lung cancer (NSCLC) accounts for more than 80% of all cancer types. Lung cancer is the cause of almost five and a half thousand deaths a year in the Czech Republic, the mortality/incidence ratio is around 85%. The reason is mainly the late recognition of the tumor only in advanced stages - stage III and IV when long-term control of the disease is a rarity. In patients with advanced-stage NSCLC, chemotherapy prolongs overall survival by less than a year on average, which is still a very disappointing result. Therefore, other treatment approaches are being developed to help change this statistic. Radiotherapy (RT) also plays an important role in the treatment of lung cancer, which has a proven therapeutic benefit in both radical and palliative indications for up to 76% of all patients.

Stereotactic Robotic Radiotherapy (SBRT) achieves extraordinary precision due to the precise definition of the target volume with maximum sparing of surrounding tissues. It also allows you to focus on bearings that show movement, especially during the breathing cycle. Radiotherapy, whether conventional or stereotactic, is a non-invasive treatment method.

The aim of the study is to verify the feasibility of consolidation SBRT - CyberKnife with subsequent maintenance chemotherapy in patients in IV. The stage of non-small cell lung cancer with a maximum of 10 metastatic foci, with acceptable toxicity, while maintaining a good quality of life. The time to progression (worsening of the disease), overall survival, the number of foci with local control, the time to the appearance of new foci, the duration of maintenance chemotherapy, and the finding of predictive molecular markers of treatment response will be evaluated.

Design: prospective, interventional trial (University Hospital Ostrava) 3 months of chemotherapy platin doublet (cDDP / CBDCA + Pemetrexed, NVB) if SD/PD: RT to primary tumour + SBRT to all oligometa (max. 10 intra / extrarnial leasions, intracranial SD / PR) SBRT V \< 100 ml, if technically possible fractionation RT (40 - 50 Gy / 16 - 20 fractions), SBRT (30 Gy / 1 fraction, 50 - 60 Gy / 3 - 5 fractions) 3 - 6 weeks ... maintenance

Preliminary examination: PET/CT, ECHO, spirometry, MR (only if neurological symptomatology)

Endpoints:

Primary Endpoints: toxicity (CTCAE ver. 4), PFS Secondary Endpoints: OS, local control, time to new lesion, duration of maintenance chemotherapy, restriction volume according to spirometry, EF

Ad hoc analysis: PDL1 expression, Ki67 status, smoking history, KPS

Restage: every three 3 months

Eligibility criteria: Inclusion Criteria:

* Patients must have biopsy-proven metastatic NSCLC (Stage IV).
* Patients must have received three months of first-line chemotherapy and achieved stable disease or partial response.
* Age ≥ 18 years
* Patients must have measurable disease at baseline.
* Patients can have up to 10 discrete active extracranial/intracranial lesions identified by PET/CT or MRI scan within 8 weeks prior to the initiation of SBRT.
* Patients must have a Karnofsky Performance Scale (KPS) \>60
* AST, ALT \& Alkaline phosphates must be ≤ 2.5x the upper limit of normal. Total bilirubin must be within the limit of normal.
* Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm³.
* Patients should have adequate renal function (serum creatinine ≤1.5 times the upper limit of normal (ULN).
* Females of childbearing potential should have a negative pregnancy test.
* Patients who would be receiving SBRT for lung tumors must have a documented forced expiratory volume in 1 second (FEV1) ≥ 1L.
* Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria:

* Patients receiving first-line erlotinib, gefitinib, or crizotinib for EGFR mutant-positive or EML4-ALK-positive NSCLC will be excluded.
* Patients who previously received radiotherapy at the primary site with CT evidence of disease progression at the primary site within 3 months following the initial radiotherapy
* Patients with serious, uncontrolled, concurrent infection(s)
* Significant weight loss (\>10%) in the prior 3 months
* Patients with cutaneous metastasis of NSCLC
* Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cancers
* Patients with more than 10 discrete extra/intracranial lesions
* Participation in any investigational drug study within 4 weeks preceding the start of study treatment
* Unwillingness to participate or inability to comply with the protocol for the duration of the study
* Patients who are pregnant; patients with reproductive capability will need to use adequate contraception during the time of participation in the study

Primary outcomes:
measure: Grade of Toxicity
timeFrame: up to 12 months
measure: Progression-Free Survival
timeFrame: up to 12 months
Secondary outcomes:
measure: Overall Survival
timeFrame: up to 12 months
measure: Time to new lesion
timeFrame: up to 12 months)
measure: Duration of maintenance chemotherapy
timeFrame: up to 12 months
measure: Restriction volume of pulmonary capacity
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
state: Moravian-Silesian Region
Study officials:
affiliation: University Hospital Ostrava
name: Tereza Paračková, MD
role: PRINCIPAL_INVESTIGATOR
References: