INTENSE: A Phase I/II Study of INhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer

NCT02764086 | Terminated Phase 1 DMC

• 1 other identifier: CTRIAL-IE (ICORG) 15-47
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  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)

  2 years post treatment

• To estimate the rate of overall survival; death from any cause is considered an event

  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.

  8 years

• To estimate the time to local failure (failure defined by RECIST V1.1 )

  8 years

• To evaluate tumour response at 6, 12 and 24 months (response measured by RECIST V1.1)

  2 years

Study Arms (1)

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

Radiation: Radiation

Interventions

Radiation RADIATION

Escalated dose of minimum 65Gy to the iGTV, with 60 Gy to PTV.

Trial Cohort Description

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (1)

St Lukes Radiation Oncology Network (SLRON) at St Luke's Hospital and St James Hospital

Dublin, Ireland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiation

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Prof John Armstrong

  St Luke's Radiation Oncology Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 21, 2016
• First Posted: May 6, 2016
• Study Start: August 10, 2016
• Primary Completion: June 5, 2020
• Study Completion: June 5, 2020
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

IE (1)