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Study of Interest of Personalized Radiotherapy Dose Redistribution in Patients With Stage III NSCLC (RTEP7)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02473133
Recruitment Status : Unknown
Verified July 2016 by Centre Henri Becquerel.
Recruitment status was:  Recruiting
First Posted : June 16, 2015
Last Update Posted : July 28, 2016
Sponsor:
Collaborator:
Intergroupe Francophone de Cancerologie Thoracique
Information provided by (Responsible Party):
Centre Henri Becquerel

Tracking Information
First Submitted Date  ICMJE June 8, 2015
First Posted Date  ICMJE June 16, 2015
Last Update Posted Date July 28, 2016
Study Start Date  ICMJE July 2015
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2015)
Local regional control rate [ Time Frame: one year ]
LCR rate (responders or stable disease) at 1 year after completion of RCT (M15 visit). Disease progression will be assessed by RECIST 1.1 criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2015)
  • Percentage of local regional control with RECIST 1.1 criteria [ Time Frame: assessed at 9 months, 15 months, 27 months and 39 months ]
    Disease progression will be assessed by RECIST 1.1 criteria
  • interval from the date of registration to date of local or regional progression [ Time Frame: 3 years ]
    the interval from the date of registration to date of local or regional progression
  • Percentage of severe (grade 3+ CTCAE, v4) radiation-induced toxicity affecting lung and oesophagus at M9 visit (early toxicity) and M15, M27, M39 visits (late toxicity), [ Time Frame: assessed at 9 months, 15 months, 27 months and 39 months ]
    Percentage of severe (grade 3+ CTCAE, v4) radiation-induced toxicity affecting lung and oesophagus at M9 visit (early toxicity) and M15, M27, M39 visits (late toxicity),
  • Percentage of patients in arm A for whom the radiotherapy dose could be increased [ Time Frame: 6.6 weeks ]
    Percentage of patients in arm A for whom the RT dose could be increased
  • correlation of progression free survival with PET measure [ Time Frame: one year ]
    standardized uptake value max and metabolic tumor volume of FDG -PET2 will be correlated with progression free survival at M15 visit
  • correlation of overall survival with PET measure [ Time Frame: one year ]
    standardized uptake value max and metabolic tumor volume of FDG -PET2 will be correlated with overall survival at M15 visit
  • Change in standardized uptake value max [ Time Frame: weeks 12 ]
    Measurements of the relative change in SUVmax from the 18F-FDG -PET1 (baseline) to the FDG -PET2 at 42 Gy defined as [(PET2- PET1) / PET1] x 100%
  • Change in metabolic volume [ Time Frame: weeks 12 ]
    Measurements of the relative change metabolic tumour volume from the 18F-FDG -PET1 (baseline) to the FDG -PET2 at 42 Gy defined as [(PET2- PET1) / PET1] x 100%
  • Overall Survival [ Time Frame: assessed at 9 months, 15 months, 27 months and 39 months ]
    overall survival after M9, M15, M27, M39 follow-up visits
  • progression-free survival [ Time Frame: assessed at 9 months, 15 months, 27 months and 39 months ]
    progression-free survival after M9, M15, M27, M39 follow-up visits
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Interest of Personalized Radiotherapy Dose Redistribution in Patients With Stage III NSCLC
Official Title  ICMJE Randomized Phase II-III Study of Personalized Radiotherapy Dose Redistribution in Patients With Inoperable Stage III Non-small Cell Lung Cancer and a Persistent FDG Uptake at 42 Grays During Concomitant Radio-chemotherapy
Brief Summary

In patients with locally advanced stage III non-small cell lung cancer, the probability of local control remains low (about 17% at 1 year). Concomitant radio-chemotherapy is the standard treatment. An increase in total radiotherapy dose (from 66 to 74 Gray) has been proposed to improve local control, with contradictory results.

Relevant FDG-PET scan images can be acquired during radio-chemotherapy, with a demonstrated prognostic impact and recently in a multicentre prospective study. A significant reduction in FDG uptake / volume (metabolic response) suggests that the radiotherapy target volume could be reduced during radiotherapy possibly improving organs at risk tolerance. Conversely, a lack of metabolic response may justify treatment intensification before the end of radiotherapy. The investigators hypothesis is to investigate the individual tumour heterogeneity on FDG-PET during radio-chemotherapy to reduce the volume to a biological target that could receive a higher total dose (personalized dose redistribution).

Detailed Description

The investigators objective is to determine whether tumour radiotherapy dose escalated up to 74 Gy in 6.6 weeks can improve the disease Local Regional Control rate at 15 months (1 year after completion of RCT) by adapting radiotherapy target volume to the metabolic response as assessed on FDG-PET/CT performed at 42 Gy of concomitant radio-chemotherapy in stage III non-small cells lung cancer and warrant more extensive phase III study.

Eligible patients will be allocated to one of 2 treatment groups:

  • Arm A: Patients in the experimental arm will receive an individualized radiotherapy prescription up to a total dose of 74 Gy given in 6.6 weeks if they have a positive FDG-PET at 42Gy.
  • Arm B: Patients in the standard arm will receive a single prescription of 66 Gy in 33 fractions in 6.6 weeks, with 2 Gy fractions given once daily, 5 days a week, without target volume reduction or adaptation (whatever the FDG-PET result).

In both arms, all patients will undergo 2 cycles of induction chemotherapy (based platinum salts) and a curative radio-chemotherapy. In both arms all fields must be treated daily.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Radiation: Personalized dose redistribution
    Patients will receive an individualized radiotherapy prescription up to a total dose of 74 Gy given in 6.6 weeks if they have a positive FDG-PET at 42Gy. An initial dose of 50 Gy will be delivered in 5 weeks (single daily fractions of 2 Gy), then an additional dose up to 24 Gy will be delivered over 1.6 week.
    Other Name: boost
  • Radiation: No personalized dose redistribution
    Patients will receive a single prescription of 66 Gy in 33 fractions in 6.6 weeks, with 2 Gy fractions given once daily, 5 days a week, without target volume reduction or adaptation (whatever the FDG-PET2 result).
Study Arms  ICMJE
  • Experimental: Personalized dose redistribution
    Patients in the will receive an individualized radiotherapy prescription up to a total dose of 74 Gy given in 6.6 weeks if they have a positive FDG-PET at 42Gy (about two thirds of patients are expected as positive). An initial dose of 50 Gy will be delivered in 5 weeks (single daily fractions of 2 Gy), then an additional dose up to 24 Gy will be delivered over 1.6 week using a twice-a-day fractionated radiotherapy.
    Intervention: Radiation: Personalized dose redistribution
  • Sham Comparator: No dose redistribution
    Patients will receive a single prescription of 66 Gy in 33 fractions in 6.6 weeks, with 2 Gy fractions given once daily, 5 days a week, without target volume reduction or adaptation (whatever the FDG-PET result).
    Intervention: Radiation: No personalized dose redistribution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 12, 2015)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients,
  • Age over 18 years and below 75-year-old,
  • Good general condition: WHO performance status ≤ 1,
  • Histological evidence of non-small cell lung cancer,
  • Measureable tumour according to RECIST 1.1 evaluation criteria,
  • Mediastinoscopy or endobronchial ultrasound to prove the histological stage N2/N3,
  • Patient eligible to curative-intent radio-chemotherapy,
  • Absence of pleural involvement, of pulmonary or extra-thoracic metastatic localisation,
  • Absence of co-morbidity contra-indicating radio-chemotherapy,
  • Lung function: FEV1 ≥ 40% of theoretical value and DLCO/VA ≥ 60% of theoretical value and PaO2 ≥ 60 mm Hg,
  • Tumour FDG uptake higher than mediastinal background noise on baseline PET/CT,
  • Haematological parameters:
  • Neutrophil count ≥ 1.5x109/L and platelet count ≥ 100x109/L,
  • Haemoglobin ≥ 9 g/dL,
  • Provisional RT plan confirming that the dose objectives (minimal dose of 62.7 Gy (95% of the prescribed dose) in 98% of target volumes and 70.3 Gy for the "boosted" volume at 74 Gy) and constraints (lungs, spinal cord) are met (ICRU83),
  • Estimated creatinine clearance ≥ 60 mL/min,
  • Signed informed consent
  • Affiliated or beneficiary of a social benefit system

Exclusion Criteria:

  • Histology other than non-small cell lung cancer,
  • Absence of FDG uptake on FDG-PET/CT scan before induction chemotherapy,
  • Patients for whom curative radiotherapy is not indicated (tumour extension, metastases, general condition, co-morbidities),
  • Significant interstitial disease on CT scan,
  • Previous neoplastic disease of less than 5 years duration or progressive (without basal cell carcinoma of the skin, in situ carcinoma of the cervix),
  • Previous thoracic radiotherapy,
  • Patient enrolled in another therapeutic trial,
  • Pregnant women or women of child-bearing potential or breast feeding mothers,
  • Adult subjects who are under protective custody or guardianship,
  • Patient unable to comply with the specific obligations of the study (geographic, social or physical reasons),
  • Uncontrolled diabetes with blood glucose ≥10 mmol/L,
  • Hypersensitivity to the active substance (FDG) or to any of the excipients,
  • Patients unable to understand the purpose of the study (language, etc.).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02473133
Other Study ID Numbers  ICMJE CHB14.04/IFCT14-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Centre Henri Becquerel
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Centre Henri Becquerel
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Intergroupe Francophone de Cancerologie Thoracique
Investigators  ICMJE
Principal Investigator: Peirre Vera, MD,PHD Centre Henri Becquerel
PRS Account Centre Henri Becquerel
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP