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

NCT05222087 | Recruiting Phase 1 DMC

• 1 other identifier: 80476
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• To assess the feasibility of the study design to be escalated without major modification directly to a randomised phase III design.

  To assess the feasibility of the study design to be escalated without major modification directly to a randomised phase III design. Technical feasibility will be assessed by the ability to deliver radiotherapy to the lung cancer primary whilst meeting dose constraints tumour prior to cycle 3 of SoC systemic therapy in metastatic NSCLC. Radiotherapy to the primary in stage IV NSCLC will be considered worthwhile to be assessed in a large randomised study if radiotherapy is feasible in \>66% of patients randomised to the radiotherapy arm.

  18 months

Secondary Outcomes (3)

• willingness to be randomised

  18 months

• safety of Radiotherapy addition using NCI CTCAE

  24 months

• PFS

  24 months

Study Arms (2)

Arm 1: SoC systemic therapy

ACTIVE COMPARATOR

Drug: SoC systemic therapy

Arm 2: radiotherapy to lung primary, delivered before cycle three of SoC systemic therapy

EXPERIMENTAL

Radiation: Radiotherapy; Drug: SoC systemic therapy

Interventions

Radiotherapy RADIATION

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

Arm 2: radiotherapy to lung primary, delivered before cycle three of SoC systemic therapy

SoC systemic therapy DRUG

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.

Arm 1: SoC systemic therapy; Arm 2: radiotherapy to lung primary, delivered before cycle three of SoC systemic therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (6)

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

NOT YET RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

NOT YET RECRUITING

Peter MacCallum Cancer Centre - Bendigo

Bendigo, Victoria, 3550, Australia

RECRUITING

Peter MacCallum Cancer Centre - Monash Cancer Centre

Bentleigh East, Victoria, 3165, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Sunshine Hospital Western Health

Sunshine, Victoria, 3000, Australia

RECRUITING

MeSH Terms

Interventions

Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Shankar Siva, A/Prof

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shankar Siva

CONTACT

+613 85595000; shankar.siva@petermac.org

CRDO

CONTACT

+61 3 8559 8872; CRDO@petermac.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: February 3, 2022
• Study Start: January 3, 2022
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6)