NSCLCPhase 1PRIME_LUNGNCT05222087
PRIME_LUNG: Primary Radiotherapy In MEtastatic Lung Cancer - A Pilot Study
A Phase 1 study testing Radiotherapy and SoC systemic therapy in people with NSCLC, run by Peter MacCallum Cancer Centre, Australia at 6 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC
- What is being tested?
- Radiotherapy and SoC systemic therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 6 sitesAustralia
- Study dates
- 3 Jan 2022to Apr 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Australia6 sites, 6 recruiting
- Recruiting
Peter MacCallum Cancer Centre - Bendigo
Bendigo, Victoria, 3550
Mark Shaw, Mark.Shaw@petermac.org
- Recruiting
Peter MacCallum Cancer Centre - Monash Cancer Centre
Bentleigh East, Victoria, 3165
Monique Youl, Monique.Youl@petermac.org
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Angie Tran, +61385597125, Angie.Tran@petermac.org
Shankar Siva
- Not yet recruiting
Gold Coast University Hospital
Southport, Queensland, 4215
Andrew Oar, Andrew.Oar@icon.team
- Recruiting
Sunshine Hospital Western Health
Sunshine, Victoria, 3000
Fiona Hegi-Johnson, fiona.hegi-johnson@petermac.org
- Not yet recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Margot Lehman, margot.lehman@health.qld.gov.au
About this study
Official title: PRIME_LUNG: Primary Radiotherapy In MEtastatic Lung Cancer. A Pilot Study
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.
Read the detailed description
PRIME-Lung is an open-label randomised pilot study designed to assess the safety and feasibility of radiotherapy to the lung primary prior to commencement of standard of care (SOC) systemic therapy in advanced lung cancer. The study is designed to assess the feasibility of the protocol, and will be escalated, without major modification, directly to a randomised phase III design. This will occur if the following objectives are met in ≥ 66% of patients:
- Receipt of radiotherapy before cycle 3 of systemic therapy.
- Ability to meet dose constraints in delivering radiotherapy to the lung primary
The secondary objectives are:
- Evaluate proportion of patients who are willing to be randomized.
- To describe toxicity within 90 days of RT delivery
- To describe progression free survival Blood samples for future translational research will also be established.
Newly diagnosed patients with advanced (Stage IV) non-small cell lung cancer (NSCLC) who have received no prior lines of systemic therapy will be invited to participate (refer to protocol for full inclusion/exclusion criteria). Consenting patients will be randomised to either:
- Arm 1: Systemic therapy alone
- Arm 2: Radiotherapy before cycle 3 of systemic therapy
The trial treatment is therefore the addition of radiotherapy before cycle 3 of SOC systemic therapy.
During treatment (standard and experimental arm) participants will be assessed for radiation toxicity and the occurrence of adverse events. The recruitment period is over 18 months, with study visits at Baseline, radiotherapy (patients in Arm 2 only), Cycle 3 of SOC systemic therapy, 12 and 24 weeks after initiation of therapy, and at disease progression. SOC CT Staging scans will occur every 6 weeks from initiation of SOC systemic therapy.
- Conditions
- NSCLC
- Being tested
- Radiotherapy, SoC systemic therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
35Gy/5# Central 40Gy/5# Large Tumours >5cm (non-central) 36Gy/12# or 40Gy/15# Ultracentral lesions 50Gy/5# Peripheral Tumours ≤5cm
SoC systemic therapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: SoC systemic therapy | Active comparator | Not described Receives: Drug: SoC systemic therapy |
| Arm 2: radiotherapy to lung primary, delivered before cycle three of SoC systemic therapy | Experimental | Not described Receives: Radiation: Radiotherapy; Drug: SoC systemic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
Secondary outcomes (3)
willingness to be randomised
evaluate the proportion of patients who are willing to be randomised after being approached for the study.
Measured: 18 months
safety of Radiotherapy addition using NCI CTCAE
The safety of the addition of radiotherapy by describing toxicity during the follow up period in each arm.
Safety will be measured as adverse events (AE) and serious adverse events (SAEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Measured: 24 months
PFS
The study will also describe progression free survival within 6 months of follow-up. PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the Investigator following principles of RECIST 1.1, or death from any cause, whichever occurs first.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2022
- Study start3 Jan 2022
- Primary completionApr 2025 (estimated)
- Study completionApr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter MacCallum Cancer Centre, Australia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shankar Siva, A/Prof, Principal investigator, Peter MacCallum Cancer Centre, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05222087
- Sponsor's protocol ID
- 80476
- Acronym
- PRIME_LUNG
- Status last verified
- Aug 2024
- First submitted
- 6 Jan 2022
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRIME_LUNG: Primary Radiotherapy In MEtastatic Lung Cancer. A Pilot Study
- ClinicalTrials.gov ID
- NCT05222087
- Acronym / sponsor ID
- PRIME_LUNG / 80476
- Conditions
- NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Peter MacCallum Cancer Centre, AustraliaUniversity, hospital or other
- Study start
- 3 Jan 2022 (actual)
- Primary completion
- Apr 2025 (estimated)
- Study completion
- Apr 2025 (estimated)
- First posted
- 3 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIME-Lung is an open-label randomised pilot study designed to assess the safety and feasibility of radiotherapy to the lung primary prior to commencement of standard of care (SOC) systemic therapy in advanced lung cancer. The study is designed to assess the feasibility of the protocol, and will be escalated, without major modification, directly to a randomised phase III design. This will occur if the following objectives are met in ≥ 66% of patients:
- Receipt of radiotherapy before cycle 3 of systemic therapy.
- Ability to meet dose constraints in delivering radiotherapy to the lung primary
The secondary objectives are:
- Evaluate proportion of patients who are willing to be randomized.
- To describe toxicity within 90 days of RT delivery
- To describe progression free survival Blood samples for future translational research will also be established.
Newly diagnosed patients with advanced (Stage IV) non-small cell lung cancer (NSCLC) who have received no prior lines of systemic therapy will be invited to participate (refer to protocol for full inclusion/exclusion criteria). Consenting patients will be randomised to either:
- Arm 1: Systemic therapy alone
- Arm 2: Radiotherapy before cycle 3 of systemic therapy
The trial treatment is therefore the addition of radiotherapy before cycle 3 of SOC systemic therapy.
During treatment (standard and experimental arm) participants will be assessed for radiation toxicity and the occurrence of adverse events. The recruitment period is over 18 months, with study visits at Baseline, radiotherapy (patients in Arm 2 only), Cycle 3 of SOC systemic therapy, 12 and 24 weeks after initiation of therapy, and at disease progression. SOC CT Staging scans will occur every 6 weeks from initiation of SOC systemic therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radiotherapy35Gy/5# Central 40Gy/5# Large Tumours >5cm (non-central) 36Gy/12# or 40Gy/15# Ultracentral lesions 50Gy/5# Peripheral Tumours ≤5cm | Radiation | Arm 2: radiotherapy to lung primary, delivered before cycle three of SoC systemic therapy |
| SoC systemic therapyPermitted 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. | Drug | Arm 1: SoC systemic therapy, Arm 2: radiotherapy to lung primary, delivered before cycle three of SoC systemic therapy |
Primary outcome
To assess the feasibility of the study design to be escalated without major modification directly to a randomised phase III design.
Time frame: 18 months
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.
3 secondary outcomes
willingness to be randomised
Time frame: 18 months
safety of Radiotherapy addition using NCI CTCAE
Time frame: 24 months
PFS
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Individual participant dataSharing planned: No
Related trials for NSCLC
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shankar Siva, A/Prof principal investigator
Peter MacCallum Cancer Centre, Australia
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Radiotherapy and SoC systemic therapy in people with NSCLC, run by Peter MacCallum Cancer Centre, Australia at 6 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shankar Siva (+613 85595000, shankar.siva@petermac.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the feasibility of the study design to be escalated without major modification directly to a randomised phase III design. (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2024.