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

Primary Purpose

Non-small Cell Lung Cancer

Status

Unknown status

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Personalized dose redistribution

No personalized dose redistribution

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring radiotherapy, dose redistribution, boost

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.).

Sites / Locations

Centre Henri BecquerelRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Personalized dose redistribution

No dose redistribution

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

Local regional control rate

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

Disease progression will be assessed by RECIST 1.1 criteria

interval from the date of registration to date of local or regional progression

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),

Percentage of patients in arm A for whom the radiotherapy dose could be increased

Percentage of patients in arm A for whom the RT dose could be increased

correlation of progression free survival with PET measure

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

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

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

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

overall survival after M9, M15, M27, M39 follow-up visits

progression-free survival

progression-free survival after M9, M15, M27, M39 follow-up visits

Full Information

NCT ID

NCT02473133

First Posted

June 8, 2015

Last Updated

July 27, 2016

Sponsor

Centre Henri Becquerel

Collaborators

Intergroupe Francophone de Cancerologie Thoracique

1. Study Identification

Unique Protocol Identification Number

NCT02473133

Brief Title

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

Acronym

RTEP7

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Unknown status

Study Start Date

July 2015 (undefined)

Primary Completion Date

December 2018 (Anticipated)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Henri Becquerel

Collaborators

Intergroupe Francophone de Cancerologie Thoracique

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer

Keywords

radiotherapy, dose redistribution, boost

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Personalized dose redistribution

Arm Type

Experimental

Arm Description

Arm Title

No dose redistribution

Arm Type

Sham Comparator

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Personalized dose redistribution

Other Intervention Name(s)

boost

Intervention Description

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.

Intervention Type

Radiation

Intervention Name(s)

No personalized dose redistribution

Intervention Description

Primary Outcome Measure Information:

Title

Local regional control rate

Description

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

Time Frame

one year

Secondary Outcome Measure Information:

Title

Percentage of local regional control with RECIST 1.1 criteria

Description

Disease progression will be assessed by RECIST 1.1 criteria

Time Frame

assessed at 9 months, 15 months, 27 months and 39 months

Title

interval from the date of registration to date of local or regional progression

Description

the interval from the date of registration to date of local or regional progression

Time Frame

3 years

Title

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),

Description

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

Title

Percentage of patients in arm A for whom the radiotherapy dose could be increased

Description

Percentage of patients in arm A for whom the RT dose could be increased

Time Frame

6.6 weeks

Title

correlation of progression free survival with PET measure

Description

standardized uptake value max and metabolic tumor volume of FDG -PET2 will be correlated with progression free survival at M15 visit

Time Frame

one year

Title

correlation of overall survival with PET measure

Description

standardized uptake value max and metabolic tumor volume of FDG -PET2 will be correlated with overall survival at M15 visit

Time Frame

one year

Title

Change in standardized uptake value max

Description

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%

Time Frame

weeks 12

Title

Change in metabolic volume

Description

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%

Time Frame

weeks 12

Title

Overall Survival

Description

overall survival after M9, M15, M27, M39 follow-up visits

Time Frame

assessed at 9 months, 15 months, 27 months and 39 months

Title

progression-free survival

Description

progression-free survival after M9, M15, M27, M39 follow-up visits

Time Frame

assessed at 9 months, 15 months, 27 months and 39 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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.).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Pierre Vera, MD, PhD

Phone

0232082258

pierre.vera@chb.unicancer.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Doriane Richard, PhD

Phone

0232082985

doriane.richard@chb.unicancer.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peirre Vera, MD,PHD

Organizational Affiliation

Centre Henri Becquerel

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Henri Becquerel

City

Rouen

ZIP/Postal Code

76038

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pierre Vera, MD, PhD

Phone

0232082258

pierre.vera@chb.unicancer.fr

First Name & Middle Initial & Last Name & Degree

Doriane Richard, PhD

Phone

0232082985

doriane.richard@chb.unicancer.fr

12. IPD Sharing Statement

Learn more about this trial

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

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