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

Purpose

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.

Condition	Intervention	Phase
Locally Advanced Non-small Cell Lung Cancer	Radiation: Radiotherapy	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Trial of Isotoxic Accelerated Radiotherapy in the Treatment of Patients With Non-small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

Further study details as provided by Wales Cancer Trials Unit:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
Phase II: Toxicity rate (grade 3 and 4) at three months. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Phase I: Chronic oesophagitis or stricture occurring/persisting two months or more after completion of radiotherapy [ Time Frame: 2 months ] [ Designated as safety issue: No ]
Pase II: Local control at three months (to include complete response, partial response and stable disease) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Phase II: Feasibility [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Phase II: Time to distant metastases measured in days [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	121
Study Start Date:	January 2012
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1A 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 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.
Experimental: Group 1B 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 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.
Experimental: Phase II 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 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.

Show Detailed Description

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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
Patient is available for follow up

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01537991

Contacts

Contact: Lisette Nixon, BSc, PhD	+44 (0)2920 687458	nixonls@cardiff.ac.uk
Contact: Robert Cowles	+44 (0)2920 687500	I-START@cardiff.ac.uk

Locations

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

Sponsors and Collaborators

Wales Cancer Trials Unit

Investigators

Principal Investigator:	Jason Lester, MBBS, MRCP, FRCR	Velindre Cancer Centre
Study Director:	Gareth Griffiths, BSc, MSc, Cstat	Wales Cancer Trials Unit

More Information

Additional Information:

I-START trial page This link exits the ClinicalTrials.gov site

UK Clinical Research Network Study Portfolio database This link exits the ClinicalTrials.gov site

ISRCTN database This link exits the ClinicalTrials.gov site

NCRI Radiotherapy Trials Quality Assurance Group This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Wales Cancer Trials Unit
ClinicalTrials.gov Identifier:	NCT01537991 History of Changes
Other Study ID Numbers:	2009/VCC/0080, ISRCTN74841904
Study First Received:	February 17, 2012
Last Updated:	February 17, 2012
Health Authority:	United Kingdom: Research Ethics Committee

Keywords provided by Wales Cancer Trials Unit:

radiotherapy
non small cell lung cancer
isotoxic

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms

Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 21, 2013