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

This study is currently recruiting participants.
Verified July 2016 by Centre Henri Becquerel
Sponsor:
ClinicalTrials.gov Identifier:
NCT02473133
First Posted: June 16, 2015
Last Update Posted: July 28, 2016
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Intergroupe Francophone de Cancerologie Thoracique
IFCT
Information provided by (Responsible Party):
Centre Henri Becquerel
  Purpose

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).


Condition Intervention Phase
Non-small Cell Lung Cancer Radiation: Personalized dose redistribution Radiation: No personalized dose redistribution Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Centre Henri Becquerel:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 150
Study Start Date: July 2015
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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).
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).

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02473133


Contacts
Contact: Pierre Vera, MD, PhD 0232082258 pierre.vera@chb.unicancer.fr
Contact: Doriane Richard, PhD 0232082985 doriane.richard@chb.unicancer.fr

Locations
France
Centre Henri Becquerel Recruiting
Rouen, France, 76038
Contact: Pierre Vera, MD, PhD    0232082258    pierre.vera@chb.unicancer.fr   
Contact: Doriane Richard, PhD    0232082985    doriane.richard@chb.unicancer.fr   
Sponsors and Collaborators
Centre Henri Becquerel
Intergroupe Francophone de Cancerologie Thoracique
IFCT
Investigators
Principal Investigator: Peirre Vera, MD,PHD Centre Henri Becquerel
  More Information

Responsible Party: Centre Henri Becquerel
ClinicalTrials.gov Identifier: NCT02473133     History of Changes
Other Study ID Numbers: CHB14.04/IFCT14-02
First Submitted: June 8, 2015
First Posted: June 16, 2015
Last Update Posted: July 28, 2016
Last Verified: July 2016

Keywords provided by Centre Henri Becquerel:
radiotherapy
dose redistribution
boost

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms