Consolidation Conventional Radiotherapy + Stereotactic Body Radiotherapy at 3 Months After First-line Chemotherapy in Stage IV Oligometastatic Non-small Cell Lung Cancer

Sponsor

University Hospital Ostrava (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04758481

Collaborator

(none)

Enrollment

Location

Arm

31.9

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Lung cancer is the main cause of death among cancer diseases, in the Czech Republic, as well as worldwide. Non-small cell lung cancer (NSCLC) is responsible for more than 80% of deaths among cancer patients. Bronchogenic carcinoma is the reason of death of almost 5.500 cases every year in the Czech Republic, the mortality/incidence ration varies around 85%. The main cause for these unfavorable findings is the late detection of the carcinoma in late stages only (III and IV), when a long-term control of the disease is exceptional. Chemotherapy is able to prolong the life of patients with NSCLC by less than one year on average, that is why new treatment approaches are being examined.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Radiation: primary tumour radiotherapy Radiation: stereotactic body radiotherapy Radiation: maintenance radiotherapy	N/A

Detailed Description

The basic treatment modality of lung cancer is radiotherapy, which has a proven therapeutic benefit in radical and palliative indications in up to 76% of all patients. Stereotactic robotic radiotherapy reaches maximum precision due to the precise definition of the target volume. In some localities, management with images has been solved using modern software instruments, which are able to visualize the tumor and monitor it during the whole course of respiratory cycle. This is directly associated with minimizing radiation of healthy tissues, especially the healthy lung parenchyma. In order to define predictive factors of survival of cancer patients, it is necessary to use molecular markers.

The aim of the study is to verify the feasibility of consolidation SBRT (Stereotactic Body RadioTherapy) - CyberKnife, with subsequent maintenance chemotherapy in patients with stage IV NSCLC, with max. 10 metastatic nidi. The main focus of the study will be on assessment of combination treatment toxicity.

The project is a phase I/II non-randomized clinical trial. Patients with stage IV NSCLC will be treated with 2-4 cycles of chemotherapy - platinum doublet (cisplatinum - cDDP/carboplatinum - CBDCA + Pemetrexed/navelibne - NVB). In cases when disease stabilization (SD)/partial resection (PR) will be achieved, based upon restaging examinations (CT), radiotherapy (RT) of the primary tumour will follow, with lymphadenopathy and SBRT of all metastatic nidi (max. 10 intra- or extracranial metastases). Standard fractionation schemes for RT and SBRT will be used (RT 40-50 Gy/16-20 fractions, SBRT 30 Gy/1 fractionation, 50-60 Gy/3-5 fractionations). At 3-6 weeks after the end of RT, maintenance treatment will be initiated in all patients treated with Peterexed. Regular restaging examinations are planned every 3 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a non-randomised study with the primary intent to treat patients with NSCLCThis is a non-randomised study with the primary intent to treat patients with NSCLC

Masking:

None (Open Label)

Masking Description:

The study is open label, no masking is being used.

Primary Purpose:

Treatment

Official Title:

Consolidation Conventional Radiotherapy + Stereotactic Body Radiotherapy of All Body Locations With the Disease at 3 Months After First Line Chemotherapy in Stage IV Oligometastatic Non-small Cell Lung Cancer, Prior to Maintenance Therapy

Anticipated Study Start Date :

May 4, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Primary tumour radiotherapy + stereotactic body radiotherapy + maintenance radiotherapy The patients, in whom disease stabilisation/partial regression will be achieved, will undergo primary tumour radiotherapy and stereotactic body radiotherapy, followed with maintenance radiotherapy.	Radiation: primary tumour radiotherapy The study subjects will undergo primary tumour radiotherapy. Radiation: stereotactic body radiotherapy The study subjects will undergo stereotactic body radiotherapy. Radiation: maintenance radiotherapy The study subjects will undergo maintenance radiotherapy.

Arm

Intervention/Treatment

Experimental: Primary tumour radiotherapy + stereotactic body radiotherapy + maintenance radiotherapy

The patients, in whom disease stabilisation/partial regression will be achieved, will undergo primary tumour radiotherapy and stereotactic body radiotherapy, followed with maintenance radiotherapy.

Radiation: primary tumour radiotherapy

The study subjects will undergo primary tumour radiotherapy.

Radiation: stereotactic body radiotherapy

The study subjects will undergo stereotactic body radiotherapy.

Radiation: maintenance radiotherapy

The study subjects will undergo maintenance radiotherapy.

Outcome Measures

Primary Outcome Measures

Acute and late toxicity [every 3 months, throughout the study duration, up to 32 months in total]
Acute and late toxicity of the combination therapy will be observed (according to Common Terminology for Clinical Adverse Event (CTCAE, version 5)
Progression-free survival [every 3 months]
Progression-free survival will be observed

Secondary Outcome Measures

Overall survival [every 3 months, throughout the study duration, up to 32 months in total]
Overall survival will be observed
Share of nidi under local control [every 3 months, throughout the study duration, up to 32 months in total]
The share of nidi under local control will be observed (in per cent/total number of nidi)
Time to new nidus formation [every 3 months, throughout the study duration, up to 32 months in total]
The time to new nidus formation will be observed
Duration of maintenance chemotherapy [every 3 months, throughout the study duration, up to 32 months in total]
The duration of maintenance chemotherapy will be observed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with previously untreated, non-resectable, stage IV NSCLC verified with histology or cytology (according to American Joint Committee on Cancer Version 8).
Patients must undergo 2-4 cycles of first-line chemotherapy, with the effect of disease stabilization or partial response.
Patients over 18 years of age.
Patients with measureable disease (on CT, PET/CT, MRI).
Patients with 3-10 extracranial/intracranial lesions confirmed on CT, PET/CT, MRI, max. 4 weeks prior to start of SBRT.
Max. 10 irradiated volumes (primary tumour + lymphadenopathy in one volume, if technically feasible).
Performance status (PS) 0-2 according to ECOG. Assessment of PS max. 7 days prior to start of treatment.
AST, ALT & ALP ≤ 2.5x norm. Total bilirubin must be within the normal range. 9. Normal function of bone marrow - Adiponectin ≥ 1.5, Haemoglobin ≥ 100, thrombo ≥ 100.
Serum creatinine ≤1.5x norm.
The entry laboratory tests must not be older than 14 days prior to start of treatment.
Negative pregnancy test and use of contraception in women of childbearing age.
Patients undergoing SBRT for pulmonary nidi must undergo entry spirometry with the value FEV1 (forced expiratory volume in 1 second) ≥ 1L.
Patients must sign informed consent.

Exclusion Criteria:

Patients with small-cell lung cancer or with mixed aetiology with SCLC.
Serious ongoing infections.
Patients with a history of haematopoiesis disorders.
Weight loss exceeding 10% within the last 3 months.
Patients with skin metastases of NSCLC.
Patients treated for other malignity within the last 5 years
Patients with more than 10 extracranial/intracranial metastases.
Malignant fluidothorax > 1 cm prior to start of treatment.
Patients treated with targeted treatment for EGFR mutation or EML-4-ALK translocation in the 1st-line (Erlotinib, Gefitinib, Afatinib, Crizotinib, …).
Patients treated with immunotherapy (anti-PD-1, anti-PD-L1 or anti-PD-L2, anti CTLA-4, …).
Participation in another clinical trial within the last month before the start of NSCLC treatment.
Inability to cooperate or comply with the study protocol.
Decision of the patient to discontinue participation in the study.
Pregnant women.