RecruitingPhase 1NCT05222087

PRIME_LUNG: Primary Radiotherapy In MEtastatic Lung Cancer - A Pilot Study

PRIME_LUNG: Primary Radiotherapy In MEtastatic Lung Cancer. A Pilot Study

Sponsor

Peter MacCallum Cancer Centre, Australia

Enrollment

40 participants

Start Date

Jan 3, 2022

Study Type

INTERVENTIONAL

Conditions

NSCLC

Summary

Outcome for patients diagnosed with advanced lung cancer remains poor; alternative treatment options are urgently needed. Studies in other metastatic cancers indicate radiotherapy to the primary tumour can improve outcomes. The investigators postulate this will also be observed in lung cancer patients. The aim of this pilot study is to assess the safety and feasibility of stereotactic ablative radiotherapy (SABR) to the lung primary prior to standard of care (SoC) systemic therapy in advanced non-small cell lung cancer (NSCLC). Forty patients with advanced (Stage IV) NSCLC will be recruited across the five Peter Mac campuses. Patients will be randomised to receive SoC systemic therapy with or without radiotherapy to the lung primary. Radiotherapy will be delivered before cycle 3 of SoC systemic therapy. Biospecimens will be collected for future translational research. The primary outcome of the study (feasibility of the protocol) will be assessed by the ability to deliver radiotherapy to the lung cancer primary, whilst meeting dose constraints. The study will also 1) evaluate proportion of patients who are willing to be randomised; 2) describe toxicity during the follow up period in each arm; 3) describe progression free survival.

Eligibility

Min Age: 18 Years

Inclusion Criteria7

Have provided written informed consent for the trial.
Be ≥ 18 years of age on day of signing informed consent.
Newly diagnosed, metastatic (stage IV), non-small cell lung cancer (NSCLC), not amenable to curative surgery or curative radiotherapy
Histological or cytologically documented NSCLC
EGFR/ALK/ROS1 Wild-type
Primary disease suitable for radiotherapy and not requiring immediate palliative irradiation
ECOG 0-1

Exclusion Criteria9

Medically unfit for systemic therapy
EGFR/ALK/ROS1 mutation positive
Has had previous thoracic radiotherapy of \> 36Gy in 12 fractions (or equivalent) within the 6 months prior to randomisation.
Has diagnosed and/or treated additional malignancy within 3 years prior to randomisation with the exception of: curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively treated early-stage cervical cancer, breast cancer or prostate cancer with no evidence of active disease. Other exceptions may be considered following consultation with the principal investigator.
Has a history of (non-infectious) pneumonitis or current pneumonitis that requires active corticosteroids with a dose equivalent of prednisolone\>10mg/d.
Has had any systemic anti-cancer therapy within 4 weeks prior to randomisation
A known diagnosis of idiopathic pulmonary fibrosis
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Uncontrolled brain metastases defined as not amenable to surgery or stereotactic radiotherapy

Interventions

RADIATIONRadiotherapy

35Gy/5# Central 40Gy/5# Large Tumours \>5cm (non-central) 36Gy/12# or 40Gy/15# Ultracentral lesions 50Gy/5# Peripheral Tumours ≤5cm

DRUGSoC systemic therapy

Permitted SoC chemoimmunotherapy for squamous patients will include single agent immunotherapy with Pembrolizumab or in combination with Carboplatin or Paclitaxel. Carbo/Paclitaxel/Pembro intravenous infusions are given every 3 weeks for cycle 1-4, followed by ongoing maintainence with Pembrolizumab from Cycle 5. For non-squamous patients, SoC chemoimmunotherapy will include single agent immunotherapy with Pembrolizumab or in combination with Carboplatin or Permetrexed. Carboplatin/Pemetrexed/Pembrolizumab infusions are given every 3 weeks for four cycles followed by maintenance with Pemetrexed/Pembrolizumab from Cycle 5.