AzTrials
AzTrials

Non Small Cell Lung Cancer NSCLCPhase 2AUSTRALNCT06680050

Phase II Study of Radiotherapy Followed by Durvalumab and Ceralasertib in Stage III NSCLC Patients With Thoracic Relapses +/- Oligometastases After PACIFIC Regimen

A Phase 2 study testing Durvalumab (MEDI4736), Ceralasertib and radiotherapy in people with Non Small Cell Lung Cancer NSCLC, run by Mario Negri Institute for Pharmacological Research at 9 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Aim of this phase 2 study is to explore the safety and efficacy of thoracic re-irradiation +/- SBRT to oligometastases (<3) followed after an interval of 2 weeks by durvalumab and ceralasertib for patients with thoracic relapses +/- oligometastases after PACIFIC or PACIFIC-like (concurrent or sequential… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer NSCLC
What is being tested?
Durvalumab (MEDI4736), Ceralasertib and radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
9 sitesin 2 countries
Study dates
7 Aug 2025to Jan 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Provision of signed, written and dated informed consent and any locally required authorization
  • Male or female aged 18 years or older
  • ECOG Performance Status of 0-2
  • Life expectancy ≥ 6 months at the start of treatment
  • Body weight >30kg
  • Maintenance treatment with durvalumab for a minimum of 3 months
Show all 16Show fewer
  • Histologically or cytologically documented locally advanced NSCLC at relapse
  • Measurable disease as defined by RECIST v1.1
  • Documented tumor cell PD-L1 status at first diagnosis and/or at relapse
  • Thoracic progression as defined by PACIFIC protocol, with or without a maximum of 3 metastatic lesions amenable to local radiotherapy (at discretion of treating center)
  • Interval of > 12 months between the end of the first thoracic radiotherapy (PACIFIC)
  • Pre-treatment whole body CT scan with i.v. contrast medium
  • Pre-treatment CT-PET scan
  • Pre-treatment brain MRI
  • Evidence of post-menopausal status, or negative urinary/serum pregnancy test for female pre-menopausal patients
  • Patient willing and able to comply with the protocol procedures for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

  • Patients who discontinued durvalumab due to local or systemic progression during the maintenance phase < 12 months after the end of CRT
  • Patients who experienced, during the maintenance phase with durvalumab after CRT, grade 3 or more documented immune-related toxicity (with the exception of fully recovered endocrine toxicities) or grade 3 or more radiation-induced pneumonitis.
  • Any unresolved toxicity NCI CTCAE from previous anticancer therapy not completely resolved or not resolved to baseline prior to screening for this study with the exception of alopecia, vitiligo, and the laboratory values defined below
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
  • Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
Show all 26Show fewer
  • Any toxicity that led to permanent discontinuation of prior immunotherapy
  • Patients with more than 3 distant metastases (non-oligometastatic disease)
  • Patients with metastatic disease progression not amenable for radical radiotherapy such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiosis of skin or lung, diffuse bone marrow metastasis, metastasis invading the GI tract, abdominal masses/abdominal organomegaly, identified by physical exam that is not measurable by reproducible imaging techniques.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • Diagnosis of ataxia telangiectasia
  • Patients harboring targetable genomic alterations, such as EGFR, HER-2 or MET exon14 skipping mutations, ALK, ROS1, RET or NTRK rearrangements. Molecular profiling can be assessed on archival tumor samples or on new tissue or liquid biopsy.
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • Concurrent participation (including the follow-up period) in another clinical study with an investigational product or during the last 4 weeks unless it is an observational (non-interventional) clinical study.
  • Any concurrent chemotherapy, immunotherapy, biological or hormonal therapy only for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Inadequate bone marrow reserve or organ function as defined below:
  • Absolute neutrophil count <1.5 x 109/L (1500/mm3)
  • Platelets <100 x 109/L (100000/mm3)
  • Haemoglobin <9.0 g/dL (5.59 mmol/L)
  • Serum bilirubin <1.5 x upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology) who will be allowed in consultation with their physician.
  • AST and ALT <2.5 x ULN.
  • Inadequate renal function: measured creatinine clearance (CL) <40 ml/min or calculated CL (according to Cockroft-Gault): <40ml/min or by 24-hour urine collection for determination of CL
  • History of active primary immunodeficiency
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • 1. Patients with vitiligo or alopecia 2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement 3. Any chronic skin condition that does not require systemic therapy 4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician 5. Patients with celiac disease controlled by diet alone 16. Female patients who are pregnant, breast-feeding, male, or female patients of reproductive potential who are not employing an effective method of birth control from screening to 90 days after the last dose of durvalumab.
  • 17. History of allogenic organ transplantation 18. Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the study drug or interpretation of patient safety or study results.

Trial locations and contacts

9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Irene De Simone, Project manager contact

+39 02 39014661

irene.desimone@marionegri.it

9 sites in 2 countries

Italy7 sites, 7 recruiting

  • ASST degli Spedali Civili di Brescia

    Brescia

    Paolo Borghetti, PI, MD, +39 02 3901 4651, paolobor82@yahoo.it

    Not yet recruiting

  • Azienda Ospedaliero Universitaria Careggi

    Florence

    Vieri Scotti, PI, MD, +39 02 3901 4651, vieri.scotti@unifi.it

    Recruiting

  • IRCCS Ospedale Policlinico San Martino, Genova

    Genova

    Carlo Genova, PI, MD, +39 02 3901 4651, carlo.genova@hsanmartino.it

    Recruiting

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan

    Diego Signorelli, PI, MD, +39 02 3901 4651, diego.signorelli@ospedaleniguarda.it

    Recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

    Andrea Riccardo Filippi, MD, Principal Investigator of the study, + 39 349 4694526, andreariccardo.filippi@istitutotumori.mi.it

    Recruiting

  • Azienda ospedaliera di Padova

    Padova

    Giulia Pasello, PI, MD, +39 02 3901 4651, giulia.pasello@unipd.it

    Not yet recruiting

  • Azienda Ospedaliero - Universitaria di Parma

    Parma

    Marcello Tiseo, PI, MD, +39 02 3901 4651, mtiseo@ao.pr.it

    Not yet recruiting

Other trials in Italy

Switzerland2 sites, 2 recruiting

  • University Hospital of Geneva

    Geneva

    André Durham Durham, PI, MD, +39 02 3901 4651, andre.durham@hug.ch

    Not yet recruiting

  • University Hospital Zurich

    Zurich

    Matthias Guckenberger, PI, +39 02 3901 4651, Matthias.Guckenberger@usz.ch

    Not yet recruiting

Other trials in Switzerland

About this study

Official title: AUSTRAL Trial: An Open-Label, Multicenter, Phase II Study Of Radiotherapy Followed By Durvalumab (MEDI4736) And Ceralasertib (AZD6738) In Stage III NSCLC Patients With Thoracic Relapses +/- Oligometastases After PACIFIC Regimen

Aim of this phase 2 study is to explore the safety and efficacy of thoracic re-irradiation +/- SBRT to oligometastases (<3) followed after an interval of 2 weeks by durvalumab and ceralasertib for patients with thoracic relapses +/- oligometastases after PACIFIC or PACIFIC-like (concurrent or sequential chemo-radiotherapy followed by maintenance durvalumab) regimens.

Being tested
Durvalumab (MEDI4736), Ceralasertib, radiotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab (MEDI4736)Drug

    Durvalumab will be administered via IV infusion at a dose of 1500 mg on day 8 Q4W until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

  • CeralasertibDrug

    Ceralasertib dose will be administered orally, 240mg BID, approximately 12 ± 2 hours apart, days 1 to 7 q28 (Q4W), up to progression or unacceptable toxicity.

  • radiotherapyRadiation

    Loco-regional recurrences of the primary tumor and regional lymph node metastases will be treated with a total dose of 36 to 50 Gy in daily fractions with a dose of 2 to 3 Gy per fraction. Two weeks from the last dose of radiotherapy, a systemic treatment with durvalumab and ceralasertib will be started.

Study groups in NCT06680050
Study groupRoleWhat they receive
Radiotherapy followed by Durvalumab+CeralasertibExperimentalNot described
Receives: Drug: Durvalumab (MEDI4736); Drug: Ceralasertib; Radiation: radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability, in terms of number of grade 3 or higher adverse events judged as at least possibly related to study treatment regimen

    Measured: within 6 months from the start of study treatment

  2. PFS

    PFS is defined as the time from the date of enrolment until the date of first disease progression or death to any cause, whichever comes first.

    Measured: 12 months

Secondary outcomes (4)

  1. ORR

    Objective response is defined as either complete response (CR) or partial response (PR) as determined by the investigator

    Measured: 12 months

  2. Efficacy in terms of PFS rate

    Measured: 6 and 12 months

  3. Efficacy in terms of OS

    OS is defined as the time from enrolment until the date of death from any cause

    Measured: 6 and 12 months

  4. Efficacy in terms of OS rate

    Measured: 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2024
  2. Study start7 Aug 2025
  3. Primary completionJun 2028 (estimated)
  4. Study completionJan 2029 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06680050
Sponsor's protocol ID
2024-515942-18-01
Acronym
AUSTRAL
Status last verified
Dec 2025
First submitted
30 Oct 2024
Last updated
18 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Filippi AR, Rulli E, Signorelli D, Willmann J, Durham A, De Simone I, Santoni A, Galli F, Carlucci L, Torri V, Lo Russo G, Addeo A, Guckenberger M. Rationale and Design of the AUSTRAL trial: An Open-Label, Multicenter, Phase II Study Evaluating Radiotherapy Followed by Durvalumab (MEDI4736) and Ceralasertib (AZD6738) in Stage III NSCLC Patients With Thoracic Relapses and/or Oligometastases After the PACIFIC Regimen. Clin Lung Cancer. 2025 Dec;26(8):e633-e638. doi: 10.1016/j.cllc.2025.07.006. Epub 2025 Jul 12.

    PubMed 40781023

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab (MEDI4736), Ceralasertib and radiotherapy in people with Non Small Cell Lung Cancer NSCLC, run by Mario Negri Institute for Pharmacological Research at 9 sites in 2 countries.

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 16 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Italy, Switzerland. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Irene De Simone, Project manager (+39 02 39014661, irene.desimone@marionegri.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability, in terms of number of grade 3 or higher adverse events judged as at least possibly related to study treatment regimen (time frame: within 6 months from the start of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06680050, which also lists 1 linked publication.

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 18 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in