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

NCT01537991 | Completed DMC

• 2 other identifiers: 2009/VCC/0080ISRCTN74841904
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 2

Brief Summary

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:

1. 1.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.
2. 2.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.

Conditions

Locally Advanced Non-small Cell Lung Cancer

Keywords

radiotherapy; non small cell lung cancer; isotoxic

Outcome Measures

Primary Outcomes (2)

• Phase I: Establish the maximum tolerated dose (MTD) to the oesophagus to use as the recommended Phase II dose.

  toxicity assessed up to 60 days after last Radiotherapy dose

• Phase II: Toxicity rate (grade 3 and 4) at three months.

  3 months

Secondary Outcomes (8)

• Phase I: Chronic oesophagitis or stricture occurring/persisting two months or more after completion of radiotherapy

  2 months

• Pase II: Local control at three months (to include complete response, partial response and stable disease)

  3 months

• Phase II: Feasibility

  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

  2 years

• Phase II: Time to distant metastases measured in days

  2 years

Study Arms (3)

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.

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.

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.

Radiation: Radiotherapy

Interventions

Radiotherapy RADIATION

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.

Group 1A; Group 1B; Phase II

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient is available for follow up

You may not qualify if:

• 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

Sponsors & Collaborators

• Lisette Nixon: lead

Study Sites (2)

Velindre Cancer Centre

Cardiff, Glamorgan, CF14 2TL, United Kingdom

Location

Clatterbridge Centre for Oncology

Liverpool, Merseyside, CH63 4JY, United Kingdom

Location

Related Links

• I-START trial page
• ISRCTN database
• NCRI Radiotherapy Trials Quality Assurance Group

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy

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)

Therapeutics

Study Officials

• Jason Lester, MBBS, MRCP, FRCR

  Velindre Cancer Centre

  PRINCIPAL INVESTIGATOR

• Gareth Griffiths, BSc, MSc, Cstat

  Wales Cancer Trials Unit

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Fellow (Senior Trial Manager in Solid Tumours)

Study Record Dates

• First Submitted: February 17, 2012
• First Posted: February 23, 2012
• Study Start: January 26, 2012
• Primary Completion: April 11, 2016
• Study Completion: December 31, 2018
• Last Updated: January 14, 2019

Record last verified: 2019-01

Locations

GB (2)