Radiotherapy Dose Complement in the Treatment of Hypoxic Lesions Patients With Stage III Non-small-cell Lung Cancer (RTEP-5)

July 27, 2016 updated by: Centre Henri Becquerel

Phase II Study of the Efficacy and Safety of a Radiotherapy Dose Complement in the Treatment of Hypoxic Lesions Identified by F-miso PET/CT in Patients With Stage III Non-small-cell Lung Cancer (NSCLC) Not Amenable to Curative Surgical Resection Who Are Candidate for Curative Radio-chemotherapy

This study will assess the efficacy and safety of a radiotherapy dose complement (boost) in the treatment of hypoxic lesions, measured by F-miso PET/CT, in patients with stage III NSCLC not amenable to surgery and candidate for chemoradiotherapy.

Preliminary studies in head and neck cancers have demonstrated the feasibility and support the medical benefit of this novel approach.

The aim of the study is to assess the efficacy and safety of a radiotherapy dose complement (boost) in this difficult medical condition for which only limited treatment options are available.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background This phase II study will assess the efficacy and safety of a radiotherapy dose complement (boost) in the treatment of hypoxic lesions, measured by F-miso PET/CT, in patients with stage III NSCLC not amenable to surgery and candidate for chemoradiotherapy.

There is a strong theoretical rationale supporting a radiotherapy dose increase in patients with hypoxic pulmonary tumour. F-miso PET enables in vivo identification and localisation of hypoxic tumoral areas, which constitute a target for an increased total dose of radiation therapy. Preliminary studies in head and neck cancers have demonstrated the feasibility and support the medical benefit of this novel approach. To date, no studies investigating non-small-cell lung cancer patients have been performed.

Given the methodological constraints, we propose a Gehan plan optimizing the number of subjects to be enrolled and the budget.

The project team has been working on imaging of radiotherapy targets for NSCLC for many years within a research group identified by the French National Cancer Institute (INCa) in 2005, and part of the axis 3 of Northwest Canceropole (Prof. Gregoire - Prof. Lartigau - Prof. Vera)2. This project was presented at an EORTC meeting "Imaging and radiotherapy" (organised by Dr. Nestlé) on May 28th 2010. It has been approved by the President of ESTRO (Prof. Gregoire) and the members of SFMN (French Society of Nuclear Medicine) and of the SFRO (French Society of Radiation Oncology) during an "Imaging and Hypoxia" Meeting in September 8th, 2010.

The aim of the study is to assess the efficacy and safety of a radiotherapy dose complement (boost) in this difficult medical condition for which only limited treatment options are available.

Objective(s) of the clinical study Main objective: to evaluate the rate of local control after dose complement in hypoxic lesions [maximum dose without the fraction of total lung volume receiving more that 20 Gy exceeding 30% of the lung (V20)], as determined by F-miso PET/CT.

Secondary objectives:

  • 3 months and 1 year toxicity
  • Percentage of patients for whom the RT dose could be increased
  • Simultaneous variation of the glucose metabolism and hypoxia during radiotherapy
  • Predictive value on 1-year survival probability of the variations in glucose metabolism and hypoxia during radiotherapy

Main inclusion criteria

  • Patients with stage III non-small-cell lung cancer candidate for curative radio-chemotherapy
  • The final inclusion is granted after completion of a dosimetric study confirming that the dose objectives (minimum dose of 60 Gy in 99% of target volume) and constraints to organs at risk can be achieved.

Main assessment criteria

- Percentage of local control as evaluated by CT (RECIST criteria) and FDG PET/CT at 3 months

Assessment criteria for hypoxia Visual analysis: centralized via SFMN net with 3 blinded readers within 8 days (Richin, JCO 2006). Definition of hypoxia and decision about boost dose.

Quantitative analysis: hypoxic fraction determined retrospectively (secondary endpoints and ancillary study). The Gross Target Volume (GTV) will be delineated on FDG PET/CT images using an adaptive method (Vauclin, PMB 2009). The contour of the GTV will be copied onto F-miso PET images after registration. Voxels with a signal to noise ratio greater than 1.2 will be considered as the hypoxic volume.

Experimental plan Assumption: to increase the local control rate at 3 months from 17% to 40%. A two-staged Gehan plan will be implemented. The assumption of therapeutic efficacy is π = 0.4 - In the first stage, 6 patients will receive a radiotherapy dose boost on the hypoxic lesions. If no local control is observed in these 6 patients, the trial will be stopped (power 0.95). In a second stage, the number of patients to be included will be determined according to the number of local controls in stage 1, the desired precision being set to ε = 0.10 (n=19 maximum).

Number of subjects required 60 patients with significant uptake on FDG-PET imaging after neo-adjuvant chemotherapy (75 pre-inclusion) will be included. Only half of these 60 patients (30) are expected to be definitely eligible with F-miso PET identifying hypoxic areas. Out these 30 eligible patients, we assume that 5 will not be evaluable, so that a total of 25 evaluable patients will be assessable.

Study Type

Interventional

Enrollment (Anticipated)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Rouen, France, 76000
        • Centre Henri Becquerel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with stage III non-small-cell lung cancer candidate for curative radio-chemotherapy
  • The final inclusion is granted after completion of a dosimetric study confirming that the dose objectives (minimum dose of 60 Gy in 99% of target volume) and constraints to organs at risk can be achieved.

Exclusion Criteria:

  • Other cancer
  • no evaluable tumor target
  • Absence of binding to FDG-PET tests before primary chemotherapy
  • Patients for which radiotherapy with curative intent is not indicated
  • History of neoplastic disease of less than 5 years or progressive
  • Patient already included in another clinical trial
  • Pregnant, likely to be or during breastfeeding
  • performance index OMS ≥2
  • Indicating renal insufficiency against Cisplatin treatment
  • Protected adults
  • Unable to submit to medical study for reasons geographical, social or physical
  • Patients with poorly controlled diabetes blood sugar ≥10 mmol/L
  • hypersensitivity to FDG or any excipients of the radiopharmaceutical
  • hypersensitivity to Fmiso or any excipients of the radiopharmaceutical
  • Patients unable to understand the study (language ...)
  • Patients not affiliated to the "sécurité social"

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the rate of local control
Time Frame: 3 month
to evaluate the rate of local control after dose complement in hypoxic lesions [maximum dose without the fraction of total lung volume receiving more that 20 Gy exceeding 30% of the lung (V20)], as determined by F-miso PET/CT.
3 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3 months and 1 year toxicity
Time Frame: 1 year
3 months and 1 year toxicity measured according CTCAE 4.0
1 year
Percentage of patients for whom the RT dose could be increased
Time Frame: 3 years
Percentage of patients for whom the RT dose could be increased
3 years
Simultaneous variation of the glucose metabolism and hypoxia during radiotherapy
Time Frame: 3 years
comparaison of both exam PETscan FDG and PETscan FMISO performed during radiotherapy
3 years
Predictive value on 1-year survival
Time Frame: 1 year
Predictive value on 1-year survival probability of the variations in glucose metabolism and hypoxia during radiotherapy
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Henri Becquerel

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (Actual)

March 1, 2016

Study Completion (Anticipated)

June 1, 2017

Study Registration Dates

First Submitted

April 11, 2012

First Submitted That Met QC Criteria

April 11, 2012

First Posted (Estimate)

April 12, 2012

Study Record Updates

Last Update Posted (Estimate)

July 28, 2016

Last Update Submitted That Met QC Criteria

July 27, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHB11-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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