Non-Small Cell Lung CancerPhase 1/2NCT02764086
INTENSE: A Phase I/II Study of INhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer
A Phase 1/2 study testing Radiation in people with Non-Small Cell Lung Cancer, run by Cancer Trials Ireland at 1 site in Ireland.
Trial summary
This is a prospective non-randomised Phase I/II study with patients recruited to escalated dose cohorts. Escalated dose to the iGTV (internal gross tumour volume), with 60 Gy to the conventional PTV (planning target volume), will be delivered to successive cohorts of participants (6-12 participants/cohort) until the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteIreland
- Study dates
- 10 Aug 2016to 5 Jun 2020
- Phase
- Phase 1/2
- 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
- 18 years of age
- ECOG (European Cooperative Oncology Group) performance status 0-2 (0-1 for concurrent chemotherapy)
- Weight loss <10% within 3 months of diagnosis
- Histological diagnosis (biopsy or cytology) of NSCLC (Squamous Cell Carcinoma (SCC), Adenocarcinoma, Large Cell).
- Eligible NSCLC stages: IIA (provided N1); IIB (including T3N0 if unresectable or unsuitable for stereotactic ablative body radiation therapy (SABR)); IIIA and IIIB
- Inoperable (as per Multi-Disciplinary Team (MDT)) or patient refuses surgery
Show all 12Show fewer
- Respiratory function:
- Forced Expiratory Volume (FEV1) ≥ 1L or ≥ 40% of predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) ≥ 40%
- Radiological confirmation of disease via a Positron Emission Tomography (PET) scan prior to registration.
- Life expectancy, from causes other than lung cancer, of greater than 12 months (as per physician's opinion)
- Females of child bearing potential (see Appendix H) must not be pregnant and must be prepared to use adequate contraception methods during treatment. Males whose female partners are of child-bearing potential must be prepared to use adequate contraception methods during treatment. Examples of effective contraception methods are a condom or a diaphragm with spermicidal jelly, or oral, injectable or implanted birth control.
- Provision of written consent in line with ICH-GCP guidelines
Who cannot join
- Previous thoracic radiation therapy
- Known co-existing or prior malignancy which is likely to interfere with treatment or assessment of outcomes
- Known distant metastases or metastatic pleural effusion
- Pancoast tumours (tumour of the pulmonary apex)
- Supraclavicular nodal involvement
- Spinal cord involvement
Show all 13Show fewer
- Patients with syndromes or conditions associated with increased radiosensitivity or development of lung fibrosis
- Suitable for SABR
- Idiopathic pulmonary fibrosis/usual interstitial pneumonia
- Uncontrolled intercurrent illness that is likely to interfere with treatment or assessment of outcomes
- Psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or lactating at the time of proposed randomisation
- Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study, or if it is felt by the research / medical team that the patient may not be able to comply with the protocol
Trial locations and contacts
1 site in 1 country.
Ireland1 site
St Lukes Radiation Oncology Network (SLRON) at St Luke's Hospital and St James Hospital
Dublin
About this study
This is a prospective non-randomised Phase I/II study with patients recruited to escalated dose cohorts. Escalated dose to the iGTV (internal gross tumour volume), with 60 Gy to the conventional PTV (planning target volume), will be delivered to successive cohorts of participants (6-12 participants/cohort) until the maximum tolerated oesophageal dose is determined. The minimum dose will be 60 Gy delivered via intensity modulated radiation therapy (IMRT) or volume modulated arc therapy (VMAT), planned on an Average Intensity Projection (AVIP) dataset.
Standard of care chemotherapy.
There will be two treatment arms; one with patients who are planned to receive neo-adjuvant or no chemotherapy, and the other with patients who are planned to receive concurrent chemotherapy.
Read the detailed description
This is a prospective non-randomised Phase I/II cohort study; please see above for Radiation Therapy and Chemotherapy treatment details
Each cohort will require a minimum of 6 and a maximum of 12 patients. Once 6 patients have been treated in a cohort a two-month break is taken before toxicity is analysed.
- If 2 or fewer patients experience a grade ≥3 toxicity, the next cohort will be enrolled and will receive an escalated dose (an additional +5 Gy at each escalation up to a maximum of 75 Gy)
- If 3 of the 6 patients experience a grade ≥3 toxicity, a further 6 patients will be recruited into that dose level
- If 4 or more patients experience a grade ≥3 toxicity then the MTD is fixed at the dose level of the previous cohort
If the cohort is extended to 12 patients, the following rules apply:
- If 4 or fewer patients experience a grade ≥3 toxicity, the next cohort will be enrolled and will receive an escalated dose.
- If 5 of the 12 patients experience a grade ≥3 toxicity, then the MTD is fixed at that dose level and recruitment continues up to a total of 24 patients at that dose level.
- If 6 or more patients experience a grade ≥3 toxicity, then the MTD is fixed at the dose level of the previous cohort.
Once the maximum dose cohort is established, patients will continue to be recruited at that dose level up to a total of 24 patients.
There will be two treatment arms; one with patients who are planned to receive neo-adjuvant or no chemotherapy, and th eother with patients who are planned to receive concurrent chemotherapy.
The concurrent and neo-adjuvant /no chemotherapy arms will then be escalated independently of each other.
For each arm the following number of patients will be required:
- Minimum number (if maximum dose level reached) = 36 (6 at 65 Gy, 6 at 70 Gy and 24 at 75 Gy)
- Maximum number (if maximum dose level reached) = 48 (12 at 65 Gy, 12 at 70 Gy and 24 at 75 Gy) A maximum of 48 patients are required to complete each arm (neo-adjuvant or none /concurrent chemotherapy) of the trial.
Acute toxicity will be assessed weekly during treatment and at 2, 4 and 8 weeks post-treatment Late toxicities will be assessed at 3, 6, 9, 12, 18 and 24 months post-treatment and annually thereafter until disease relapse / patient withdrawal / patient death.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Radiation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiationRadiation
Escalated dose of minimum 65Gy to the iGTV, with 60 Gy to PTV.
| Study group | Role | What they receive |
|---|---|---|
| Trial Cohort Description | Other | Escalated dose of min 65Gy to the iGTV, with 60Gy to PTV delivered to successive cohorts of patients(pts) until the MTD oesophageal dose is determined. Toxicity will be analysed 2 months post 6pts treated in a cohort.
If: ≤2pts have ≥G3 toxicity, next cohort will be enrolled \& receive escalated dose (an additional +5Gy at each escalation upto max 75Gy)/3 of 6pts have ≥G3 toxicity, a further 6pts will be recruited into that dose level/≥4pts have ≥G3 toxicity, the MTD is fixed at dose level of previous cohort
Cohort is extended to 12pts:
If: ≤4pts have ≥G3 toxicity, next cohort will be enrolled \& receive escalated dose/5 of 12pts have ≥G3 toxicity, the MTD is fixed at that dose level \& recruitment continues up to 24pts/≥6pts have ≥G3 toxicity, the MTD is fixed at the dose level of previous cohort.
Once the max dose cohort is established, recruiting will continue at that dose until 24pts. Concurrent \& neo-adjuvant/no chemotherapy arms will be escalated independently of each other Receives: Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safe delivery of an achievable level of dose escalation in a dose escalated and intensified RT regime delivered via VMAT/IMRT and focused on the GTV by the proportion of grade ≥3 toxicities determined to be related to RT
Measured: 4 years 3 months
Secondary outcomes (9)
To compare grade ≥3 toxicity 3, 6, 9, 12, 18 and 24 months, post-treatment, graded by NCI-CTCAE Version 4 (V4)
Measured: 2 years post treatment
To estimate the rate of overall survival; death from any cause is considered an event
Measured: 8 years
To estimate the rate of disease-free survival. All disease recurrences will be recorded. In disease-free survival, any tumour recurrence, development of distant metastases or death is considered an event.
Measured: 8 years
To estimate the time to local failure (failure defined by RECIST V1.1 )
Measured: 8 years
To evaluate tumour response at 6, 12 and 24 months (response measured by RECIST V1.1)
Measured: 2 years
The estimate the time to distant metastases as assessed by imaging or biopsy
Measured: 8 years
To assess Quality of life according to the EORTC QLQ-C30 and EORTC QLQ-LC13
Measured: 8 years
To assess the MTD to the oesophagus. The MTD is defined as the highest dose that does not cause unacceptable toxicities. Toxicities of interest are any CTCAE V4 grade ≥3 oesophageal toxicity determined to be related to radiation therapy.
Measured: 5 years
The change in pulmonary function post-treatment will be analysed by calculating the differences in measurements from baseline to the 1-year follow-up
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study start10 Aug 2016
- Primary completion5 Jun 2020
- Study completion5 Jun 2020
Why it stopped: Accrual lower than anticipated and not expected to improve
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective non-randomised Phase I/II study with patients recruited to escalated dose cohorts. Escalated dose to the iGTV (internal gross tumour volume), with 60 Gy to the conventional PTV (planning target volume), will be delivered to successive cohorts of participants (6-12 participants/cohort) until the maximum tolerated oesophageal dose is determined. The minimum dose delivered to the iGTV will be 65 Gy, with 60 Gy to the PTV, delivered via intensity modulated radiation therapy (IMRT) or volume modulated arc therapy (VMAT), planned on an Average Intensity Projection (AVIP) dataset.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Trials Ireland
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Prof John Armstrong, Principal investigator, St Luke's Radiation Oncology Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02764086
- Sponsor's protocol ID
- CTRIAL-IE (ICORG) 15-47
- Status last verified
- Apr 2026
- First submitted
- 21 Apr 2016
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INTENSE: A Phase I/II Study of INhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer
- ClinicalTrials.gov ID
- NCT02764086
- Acronym / sponsor ID
- CTRIAL-IE (ICORG) 15-47
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Accrual lower than anticipated and not expected to improve
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Cancer Trials IrelandResearch network
- Study start
- 10 Aug 2016 (actual)
- Primary completion
- 5 Jun 2020 (actual)
- Study completion
- 5 Jun 2020 (actual)
- First posted
- 6 May 2016 (estimated)
- 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.
This is a prospective non-randomised Phase I/II study with patients recruited to escalated dose cohorts. Escalated dose to the iGTV (internal gross tumour volume), with 60 Gy to the conventional PTV (planning target volume), will be delivered to successive cohorts of participants (6-12 participants/cohort) until the maximum tolerated oesophageal dose is determined. The minimum dose will be 60 Gy delivered via intensity modulated radiation therapy (IMRT) or volume modulated arc therapy (VMAT), planned on an Average Intensity Projection (AVIP) dataset.
Standard of care chemotherapy.
There will be two treatment arms; one with patients who are planned to receive neo-adjuvant or no chemotherapy, and the other with patients who are planned to receive concurrent chemotherapy.
Detailed description
This is a prospective non-randomised Phase I/II cohort study; please see above for Radiation Therapy and Chemotherapy treatment details
Each cohort will require a minimum of 6 and a maximum of 12 patients. Once 6 patients have been treated in a cohort a two-month break is taken before toxicity is analysed.
- If 2 or fewer patients experience a grade ≥3 toxicity, the next cohort will be enrolled and will receive an escalated dose (an additional +5 Gy at each escalation up to a maximum of 75 Gy)
- If 3 of the 6 patients experience a grade ≥3 toxicity, a further 6 patients will be recruited into that dose level
- If 4 or more patients experience a grade ≥3 toxicity then the MTD is fixed at the dose level of the previous cohort
If the cohort is extended to 12 patients, the following rules apply:
- If 4 or fewer patients experience a grade ≥3 toxicity, the next cohort will be enrolled and will receive an escalated dose.
- If 5 of the 12 patients experience a grade ≥3 toxicity, then the MTD is fixed at that dose level and recruitment continues up to a total of 24 patients at that dose level.
- If 6 or more patients experience a grade ≥3 toxicity, then the MTD is fixed at the dose level of the previous cohort.
Once the maximum dose cohort is established, patients will continue to be recruited at that dose level up to a total of 24 patients.
There will be two treatment arms; one with patients who are planned to receive neo-adjuvant or no chemotherapy, and th eother with patients who are planned to receive concurrent chemotherapy.
The concurrent and neo-adjuvant /no chemotherapy arms will then be escalated independently of each other.
For each arm the following number of patients will be required:
- Minimum number (if maximum dose level reached) = 36 (6 at 65 Gy, 6 at 70 Gy and 24 at 75 Gy)
- Maximum number (if maximum dose level reached) = 48 (12 at 65 Gy, 12 at 70 Gy and 24 at 75 Gy) A maximum of 48 patients are required to complete each arm (neo-adjuvant or none /concurrent chemotherapy) of the trial.
Acute toxicity will be assessed weekly during treatment and at 2, 4 and 8 weeks post-treatment Late toxicities will be assessed at 3, 6, 9, 12, 18 and 24 months post-treatment and annually thereafter until disease relapse / patient withdrawal / patient death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective non-randomised Phase I/II study with patients recruited to escalated dose cohorts. Escalated dose to the iGTV (internal gross tumour volume), with 60 Gy to the conventional PTV (planning target volume), will be delivered to successive cohorts of participants (6-12 participants/cohort) until the maximum tolerated oesophageal dose is determined. The minimum dose delivered to the iGTV will be 65 Gy, with 60 Gy to the PTV, delivered via intensity modulated radiation therapy (IMRT) or volume modulated arc therapy (VMAT), planned on an Average Intensity Projection (AVIP) dataset.
| Arm | Type | Receives |
|---|---|---|
| Trial Cohort Description | Other | Radiation: RadiationEscalated dose of min 65Gy to the iGTV, with 60Gy to PTV delivered to successive cohorts of patients(pts) until the MTD oesophageal dose is determined. Toxicity will be analysed 2 months post 6pts treated in a cohort. If: ≤2pts have ≥G3 toxicity, next cohort will be enrolled \& receive escalated dose (an additional +5Gy at each escalation upto max 75Gy)/3 of 6pts have ≥G3 toxicity, a further 6pts will be recruited into that dose level/≥4pts have ≥G3 toxicity, the MTD is fixed at dose level of previous cohort Cohort is extended to 12pts: If: ≤4pts have ≥G3 toxicity, next cohort will be enrolled \& receive escalated dose/5 of 12pts have ≥G3 toxicity, the MTD is fixed at that dose level \& recruitment continues up to 24pts/≥6pts have ≥G3 toxicity, the MTD is fixed at the dose level of previous cohort. Once the max dose cohort is established, recruiting will continue at that dose until 24pts. Concurrent \& neo-adjuvant/no chemotherapy arms will be escalated independently of each other |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 18 years of age
- ECOG (European Cooperative Oncology Group) performance status 0-2 (0-1 for concurrent chemotherapy)
- Weight loss <10% within 3 months of diagnosis
- Histological diagnosis (biopsy or cytology) of NSCLC (Squamous Cell Carcinoma (SCC), Adenocarcinoma, Large Cell).
- Eligible NSCLC stages: IIA (provided N1); IIB (including T3N0 if unresectable or unsuitable for stereotactic ablative body radiation therapy (SABR)); IIIA and IIIB
Key exclusion criteria (13 listed)
- Previous thoracic radiation therapy
- Known co-existing or prior malignancy which is likely to interfere with treatment or assessment of outcomes
- Known distant metastases or metastatic pleural effusion
- Pancoast tumours (tumour of the pulmonary apex)
- Supraclavicular nodal involvement
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 |
|---|---|---|
| RadiationEscalated dose of minimum 65Gy to the iGTV, with 60 Gy to PTV. | Radiation | Trial Cohort Description |
Primary outcome
To assess the safe delivery of an achievable level of dose escalation in a dose escalated and intensified RT regime delivered via VMAT/IMRT and focused on the GTV by the proportion of grade ≥3 toxicities determined to be related to RT
Time frame: 4 years 3 months
9 secondary outcomes
To compare grade ≥3 toxicity 3, 6, 9, 12, 18 and 24 months, post-treatment, graded by NCI-CTCAE Version 4 (V4)
Time frame: 2 years post treatment
To estimate the rate of overall survival; death from any cause is considered an event
Time frame: 8 years
To estimate the rate of disease-free survival. All disease recurrences will be recorded. In disease-free survival, any tumour recurrence, development of distant metastases or death is considered an event.
Time frame: 8 years
To estimate the time to local failure (failure defined by RECIST V1.1 )
Time frame: 8 years
To evaluate tumour response at 6, 12 and 24 months (response measured by RECIST V1.1)
Time frame: 2 years
The estimate the time to distant metastases as assessed by imaging or biopsy
Time frame: 8 years
To assess Quality of life according to the EORTC QLQ-C30 and EORTC QLQ-LC13
Time frame: 8 years
To assess the MTD to the oesophagus. The MTD is defined as the highest dose that does not cause unacceptable toxicities. Toxicities of interest are any CTCAE V4 grade ≥3 oesophageal toxicity determined to be related to radiation therapy.
Time frame: 5 years
The change in pulmonary function post-treatment will be analysed by calculating the differences in measurements from baseline to the 1-year follow-up
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Accrual lower than anticipated and not expected to improve). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Non-Small Cell Lung Cancer
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.
Prof John Armstrong principal investigator
St Luke's Radiation Oncology Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Radiation in people with Non-Small Cell Lung Cancer, run by Cancer Trials Ireland at 1 site in Ireland.
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 12 inclusion and 13 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: stopped early, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. 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 combined 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.
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?
The study was stopped early (reason given: Accrual lower than anticipated and not expected to improve). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safe delivery of an achievable level of dose escalation in a dose escalated and intensified RT regime delivered via VMAT/IMRT and focused on the GTV by the proportion of grade ≥3 toxicities determined to be related to RT (time frame: 4 years 3 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 13 Apr 2026.