Locally Advanced Non-small Cell Lung CancerI-STARTNCT01537991

ISoToxic Accelerated RadioTherapy in Locally Advanced Non-small Cell Lung Cancer: The Phase I/II I-START Trial

A study testing Radiotherapy in people with Locally Advanced Non-small Cell Lung Cancer, run by Lisette Nixon at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 16 years and older
Conditions the study is for: Locally Advanced Non-small Cell Lung Cancer
What is being tested?: Radiotherapy
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 81 participants
Where: 2 sitesUnited Kingdom
Study dates: 26 Jan 2012to 31 Dec 2018
Phase: Interventional
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 16 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Histologically or cytologically confirmed stage II - IIIb NSCLC (see appendix II)
Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery
Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre
WHO Performance Status 0 or 1 (Appendix III)
Adequate respiratory function: FEV1 ≥ 1.0 litre, DLco (transfer factor) ≥ 40% of predicted and Kco (DLco/VA) > 40% predicted on baseline lung function tests
Blood Haemoglobin ≥ 10g/dL

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No prior thoracic radiotherapy
Age ≥ 16 years
Considered fit to receive trial treatment
Estimated life expectancy of more than 3 months
Written informed consent obtained
Patient consents for electronic CT scan and planning data to be used for future research
Patient is available for follow up

Who cannot join

Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease)
Previous or current malignant disease likely to interfere with protocol treatment
Pancoast tumours
Connective tissue disorders (e.g. Scleroderma, Systemic Lupus Erythematosus)
Interstitial lung disease
Women who are pregnant or lactating
Women of childbearing potential who are not using adequate contraceptive precautions

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

Velindre Cancer Centre
Cardiff, Glamorgan, CF14 2TL
Clatterbridge Centre for Oncology
Liverpool, Merseyside, CH63 4JY

Other trials in United Kingdom

About this study

Official title: A Phase I/II Trial of Isotoxic Accelerated Radiotherapy in the Treatment of Patients With Non-small Cell Lung Cancer

The I-START trial is designed to determine the highest doses of radiotherapy that can safely be used in locally advanced non-small cell lung cancer (NSCLC). Patients with NSCLC who are expected to live longer than three months and are fit to receive radical radiotherapy (radiotherapy given with curative intent) will be eligible to participate. All trial participants will receive 20 doses (called fractions) of radiotherapy. Evidence is available that suggests increasing the dose of radiotherapy given per fraction may improve both local control of the cancer and survival in some patients. However, high dose radiotherapy can damage normal tissues as well as the tumour. The dose of radiotherapy that can be used to treat lung cancer is limited by the normal tissues close to the cancer. For most of these normal tissues (lung, spinal cord and heart) the maximum safe radiotherapy dose that can be given is known. The maximum safe dose of radiotherapy for the oesophagus (gullet) is not currently known.

The trial will be split into two parts:

For those participants where the oesophagus will receive a high dose of radiation due to it lying close to the cancer, the first part of the trial will establish the maximum safe dose of radiotherapy to the oesophagus. The first group of participants will receive a slightly higher dose than is currently used to treat lung cancer. If these participants do not have any significant side effects, a second group of participants will receive a slightly higher dose than the first group. This process will continue incrementally until side effects from the treatment become evident, thus demonstrating the maximum dose that can safely be given. Once the maximum safe dose to the oesophagus is known this will be classed as the recommended Phase II dose and all further patients entering the trial will receive no more than this dose to the oesophagus.
For those participants where the cancer is a safe distance from their oesophagus, the highest dose of radiotherapy that does not exceed the known safe dose limits of the normal structures (lung, spinal cord and heart) will be used.

The findings of both parts of this study will determine whether increasing the dose of radiotherapy for NSCLC patients is a tolerable, safe and effective treatment. If the results are positive then this new treatment may be compared against the best currently available standard treatments in a future larger randomised (Phase III) trial.

Read the detailed description

Main inclusion criteria:

Histologically or cytologically confirmed stage II - IIIb NSCLC (see appendix II)
Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery
Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre
WHO Performance Status 0 or 1 (Appendix III)
Adequate respiratory function: FEV1 ≥ 1.0 litre, DLco (transfer factor) ≥ 40% of predicted and Kco (DLco/VA) > 40% predicted on baseline lung function tests
Blood Haemoglobin ≥ 10g/dL
No prior thoracic radiotherapy
Age ≥ 16 years
Considered fit to receive trial treatment
Estimated life expectancy of more than 3 months
Written informed consent obtained
Patient consents for electronic CT scan and planning data to be used for future research

Main exclusion criteria:

Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease)
Previous or current malignant disease likely to interfere with protocol treatment
Pancoast tumours
Connective tissue disorders (e.g. Scleroderma, Systemic Lupus Erythematosus)
Interstitial lung disease
Women who are pregnant or lactating
Women of childbearing potential who are not using adequate contraceptive precautions Primary outcome measure: Phase I:

Establish the maximum tolerated dose (MTD) to the oesophagus to use as the recommended Phase II dose. Phase II:
Toxicity rate (grade 3 and 4) at three months. Secondary outcome measures Phase I:
Chronic oesophagitis or stricture occurring/persisting two months or more after completion of radiotherapy Phase II:
Local control at three months (to include complete response, partial response and stable disease)
Feasibility
Time to Local Progression; measured in days from the day of trial entry to the date of first clinical evidence of progressive disease at the primary site
Time to distant metastases measured in days
Overall Survival; measured in days, from the day of trial entry to the day of death (from any cause)
Toxicity; pulmonary, oesophageal, spinal cord and cardiac grade 3 or 4 toxicity occurring up to three months after radiotherapy
Radiotherapy Quality Assurance. A detailed QA program will be in place to ensure adherence to the protocol. Major and minor deviations will be documented

Conditions: Locally Advanced Non-small Cell Lung Cancer
Being tested: Radiotherapy
Keywords: radiotherapy, non small cell lung cancer, isotoxic
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.

RadiotherapyRadiation
All patients will receive radiotherapy to the primary lung tumour and any demonstrated nodal involvement. Patients will be given radiotherapy of a dose between 58 and 65Gy in 20 fractions. Dose will be determined by the patients' group.

Study groups in NCT01537991
Study group	Role	What they receive
Group 1A	Experimental	Group 1A is where less than or equal to 6.5cm length of oesophagus is lying with the Planning Target Volume. Dose will be between 58 and 65Gy determined by current trial cohort in Phase I. Receives: Radiation: Radiotherapy
Group 1B	Experimental	Group 1A is where more than 6.5cm length of oesophagus is lying with the Planning Target Volume. Dose will be between 58 and 65Gy determined by current trial cohort in Phase I. Receives: Radiation: Radiotherapy
Phase II	Experimental	All patients will receive radiotherapy to a maximum dose of 65Gy in 20 fractions. The dose to the individual patient will be determined by their individual dose constraints for organs at risk. Receives: Radiation: Radiotherapy

What is being measured

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

Phase I: Establish the maximum tolerated dose (MTD) to the oesophagus to use as the recommended Phase II dose.
Measured: toxicity assessed up to 60 days after last Radiotherapy dose
Phase II: Toxicity rate (grade 3 and 4) at three months.
Measured: 3 months

Secondary outcomes (8)

Phase I: Chronic oesophagitis or stricture occurring/persisting two months or more after completion of radiotherapy
Measured: 2 months
Pase II: Local control at three months (to include complete response, partial response and stable disease)
Measured: 3 months
Phase II: Feasibility
Measured: 2 years
Phase II: Time to Local Progression; measured in days from the day of trial entry to the date of first clinical evidence of progressive disease at the primary site
Measured: 2 years
Phase II: Time to distant metastases measured in days
Measured: 2 years
Phase II: Overall Survival; measured in days, from the day of trial entry to the day of death (from any cause)
Measured: 2 years
Phase II: Toxicity; pulmonary, oesophageal, spinal cord and cardiac grade 3 or 4 toxicity occurring up to three months after radiotherapy
Measured: 3 months
Phase II: Radiotherapy Quality Assurance. A detailed QA program will be in place to ensure adherence to the protocol. Major and minor deviations will be documented
Measured: 2 years

Timeline

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

26 Jan 201231 Dec 2018

First posted23 Feb 2012 (estimated)
Study start26 Jan 2012
Primary completion11 Apr 2016
Study completion31 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Locally Advanced 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 N/A
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 81 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01537991
Sponsor's protocol ID: 2009/VCC/0080
Other IDs: ISRCTN74841904
Acronym: I-START
Status last verified: Jan 2019
First submitted: 17 Feb 2012
Last updated: 14 Jan 2019
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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)
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RecruitingPhase 3
Study of Daraxonrasib (RMC-6236) in Patients With RAS Mutated NSCLC (RASolve 301)
NSCLC (Non-small Cell Lung Cancer), Non-Small Cell Lung Cancer
Not yet recruitingPhase 2
Phase II Study to Evaluate Telisotuzumab Adizutecan in Combination With RC148(ABBV-1480) as First-Line Treatment for Patients With Non-Squamous Non-Small-Cell Lung Cancer
Patients With Locally Advanced or Metastatic Non-Squamous NSCLC Requiring First-Line Treatment and no Driver Gene Alterations Confirmed by Histology or Cytology
RecruitingPhase 3
A Study to Evaluate Pumitamig Versus Durvalumab Following Concurrent Chemoradiation Therapy in Participants With Unresectable Stage III Non-small Cell Lung Cancer (NSCLC) (ROSETTA Lung-201)
Non-small Cell Lung Cancer (NSCLC)
RecruitingPhase 3
A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Non-small Cell Lung Cancer, HER2 Mutation

All Locally Advanced Non-small Cell Lung Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Trial of Isotoxic Accelerated Radiotherapy in the Treatment of Patients With Non-small Cell Lung Cancer
ClinicalTrials.gov ID: NCT01537991
Acronym / sponsor ID: I-START / 2009/VCC/0080
Conditions: Locally Advanced Non-small Cell Lung Cancer
Keywords: radiotherapy, non small cell lung cancer, isotoxic
Study type: Interventional
Recruitment status: Completed
Enrolment: 81 participants (actual)
Lead sponsor: Lisette NixonOther government
Study start: 26 Jan 2012 (actual)
Primary completion: 11 Apr 2016 (actual)
Study completion: 31 Dec 2018 (actual)
First posted: 23 Feb 2012 (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.

The trial will be split into two parts:

For those participants where the oesophagus will receive a high dose of radiation due to it lying close to the cancer, the first part of the trial will establish the maximum safe dose of radiotherapy to the oesophagus. The first group of participants will receive a slightly higher dose than is currently used to treat lung cancer. If these participants do not have any significant side effects, a second group of participants will receive a slightly higher dose than the first group. This process will continue incrementally until side effects from the treatment become evident, thus demonstrating the maximum dose that can safely be given. Once the maximum safe dose to the oesophagus is known this will be classed as the recommended Phase II dose and all further patients entering the trial will receive no more than this dose to the oesophagus.
For those participants where the cancer is a safe distance from their oesophagus, the highest dose of radiotherapy that does not exceed the known safe dose limits of the normal structures (lung, spinal cord and heart) will be used.

Detailed description

Main inclusion criteria:

Histologically or cytologically confirmed stage II - IIIb NSCLC (see appendix II)
Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery
Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre
WHO Performance Status 0 or 1 (Appendix III)
Adequate respiratory function: FEV1 ≥ 1.0 litre, DLco (transfer factor) ≥ 40% of predicted and Kco (DLco/VA) > 40% predicted on baseline lung function tests
Blood Haemoglobin ≥ 10g/dL
No prior thoracic radiotherapy
Age ≥ 16 years
Considered fit to receive trial treatment
Estimated life expectancy of more than 3 months
Written informed consent obtained
Patient consents for electronic CT scan and planning data to be used for future research

Main exclusion criteria:

Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease)
Previous or current malignant disease likely to interfere with protocol treatment
Pancoast tumours
Connective tissue disorders (e.g. Scleroderma, Systemic Lupus Erythematosus)
Interstitial lung disease
Women who are pregnant or lactating
Women of childbearing potential who are not using adequate contraceptive precautions Primary outcome measure: Phase I:

Establish the maximum tolerated dose (MTD) to the oesophagus to use as the recommended Phase II dose. Phase II:
Toxicity rate (grade 3 and 4) at three months. Secondary outcome measures Phase I:
Chronic oesophagitis or stricture occurring/persisting two months or more after completion of radiotherapy Phase II:
Local control at three months (to include complete response, partial response and stable disease)
Feasibility
Time to Local Progression; measured in days from the day of trial entry to the date of first clinical evidence of progressive disease at the primary site
Time to distant metastases measured in days
Overall Survival; measured in days, from the day of trial entry to the day of death (from any cause)
Toxicity; pulmonary, oesophageal, spinal cord and cardiac grade 3 or 4 toxicity occurring up to three months after radiotherapy
Radiotherapy Quality Assurance. A detailed QA program will be in place to ensure adherence to the protocol. Major and minor deviations will be documented

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Group 1A	Experimental	Radiation: RadiotherapyGroup 1A is where less than or equal to 6.5cm length of oesophagus is lying with the Planning Target Volume. Dose will be between 58 and 65Gy determined by current trial cohort in Phase I.
Group 1B	Experimental	Radiation: RadiotherapyGroup 1A is where more than 6.5cm length of oesophagus is lying with the Planning Target Volume. Dose will be between 58 and 65Gy determined by current trial cohort in Phase I.
Phase II	Experimental	Radiation: RadiotherapyAll patients will receive radiotherapy to a maximum dose of 65Gy in 20 fractions. The dose to the individual patient will be determined by their individual dose constraints for organs at risk.

Who may qualify

Ages: 16 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (13 listed)

Histologically or cytologically confirmed stage II - IIIb NSCLC (see appendix II)
Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery
Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre
WHO Performance Status 0 or 1 (Appendix III)
Adequate respiratory function: FEV1 ≥ 1.0 litre, DLco (transfer factor) ≥ 40% of predicted and Kco (DLco/VA) > 40% predicted on baseline lung function tests

Key exclusion criteria (7 listed)

Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease)
Previous or current malignant disease likely to interfere with protocol treatment
Pancoast tumours
Connective tissue disorders (e.g. Scleroderma, Systemic Lupus Erythematosus)
Interstitial lung disease

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
RadiotherapyAll patients will receive radiotherapy to the primary lung tumour and any demonstrated nodal involvement. Patients will be given radiotherapy of a dose between 58 and 65Gy in 20 fractions. Dose will be determined by the patients' group.	Radiation	Group 1A, Group 1B, Phase II

Primary outcome

Phase I: Establish the maximum tolerated dose (MTD) to the oesophagus to use as the recommended Phase II dose.
Time frame: toxicity assessed up to 60 days after last Radiotherapy dose
Phase II: Toxicity rate (grade 3 and 4) at three months.
Time frame: 3 months

8 secondary outcomes

Phase I: Chronic oesophagitis or stricture occurring/persisting two months or more after completion of radiotherapy
Time frame: 2 months
Pase II: Local control at three months (to include complete response, partial response and stable disease)
Time frame: 3 months
Phase II: Feasibility
Time frame: 2 years
Phase II: Time to Local Progression; measured in days from the day of trial entry to the date of first clinical evidence of progressive disease at the primary site
Time frame: 2 years
Phase II: Time to distant metastases measured in days
Time frame: 2 years
Phase II: Overall Survival; measured in days, from the day of trial entry to the day of death (from any cause)
Time frame: 2 years
Phase II: Toxicity; pulmonary, oesophageal, spinal cord and cardiac grade 3 or 4 toxicity occurring up to three months after radiotherapy
Time frame: 3 months
Phase II: Radiotherapy Quality Assurance. A detailed QA program will be in place to ensure adherence to the protocol. Major and minor deviations will be documented
Time frame: 2 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2019.
I-START trial pageLink provided by the sponsor.
ISRCTN databaseLink provided by the sponsor.
NCRI Radiotherapy Trials Quality Assurance GroupLink provided by the sponsor.

Related trials for Locally Advanced 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
RecruitingPhase 3
Study of Daraxonrasib (RMC-6236) in Patients With RAS Mutated NSCLC (RASolve 301)
NSCLC (Non-small Cell Lung Cancer), Non-Small Cell Lung Cancer
Not yet recruitingPhase 2
Phase II Study to Evaluate Telisotuzumab Adizutecan in Combination With RC148(ABBV-1480) as First-Line Treatment for Patients With Non-Squamous Non-Small-Cell Lung Cancer
Patients With Locally Advanced or Metastatic Non-Squamous NSCLC Requiring First-Line Treatment and no Driver Gene Alterations Confirmed by Histology or Cytology
RecruitingPhase 3
A Study to Evaluate Pumitamig Versus Durvalumab Following Concurrent Chemoradiation Therapy in Participants With Unresectable Stage III Non-small Cell Lung Cancer (NSCLC) (ROSETTA Lung-201)
Non-small Cell Lung Cancer (NSCLC)
RecruitingPhase 3
A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Non-small Cell Lung Cancer, HER2 Mutation

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.

Jason Lester, MBBS, MRCP, FRCR principal investigator

Velindre Cancer Centre

Gareth Griffiths, BSc, MSc, Cstat study director

Wales Cancer Trials Unit

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Radiotherapy in people with Locally Advanced Non-small Cell Lung Cancer, run by Lisette Nixon at 2 sites in United Kingdom.

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 13 inclusion and 7 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: finished, as of the sponsor's last update on 14 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Phase I: Establish the maximum tolerated dose (MTD) to the oesophagus to use as the recommended Phase II dose. (time frame: toxicity assessed up to 60 days after last Radiotherapy dose). 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 NCT01537991.

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 14 Jan 2019.