Dose Escalation by Boosting Radiation Dose Within the Primary Tumor Using FDG-PET-CT Scan in Stage IB, II and III NSCLC (PET Boost)

• ClinicalTrials.gov Identifier: NCT01024829
• Recruitment Status: Active, not recruiting
• First Posted: December 3, 2009
• Last Update Posted: April 16, 2020
• Sponsor: The Netherlands Cancer Institute
• Collaborator: European Union
• Information provided by (Responsible Party): The Netherlands Cancer Institute

Study Description

Brief Summary:

Increasing ("boosting") the radiation dose for patients with non-small cell lung carcinoma to the individual maximal dose which can safely be given. The question is if patients should receive this boost on the whole tumor on part of the tumor. Therefore patients are randomized for one of these two treatment options. All patients will receive 24 radiations. Dose increasement will be enabled by a so called integrated boost.

Furthermore:

- PET imaging of hypoxia using [18F]HX4, single injection and then PET CT scanning two and four hours post injection.

Condition or disease	Intervention/treatment	Phase
NSCLC	Radiation: Radiotherapy	Not Applicable

Detailed Description:

A randomized phase II study will be conducted in patients with inoperable stage IB, II or III non-small cell lung cancer (NSCLC). The patients will be randomized to receive the standard 66 Gy given in 24 fractions of 2.75 Gy with an integrated boost to the primary tumor as a whole (Arm A) or with an integrated boost to the 50% SUVmax area of the primary tumor (of the pre-treatment FDG-PET scan) (Arm B). Both treatment arms may be combined with chemotherapy (concurrent or sequential). Patients fulfilling the eligibility criteria will be registered in the study, and an initial radiotherapy treatment planning will be performed. When an integrated boost to the primary tumor as a whole up to 72 Gy is not possible because of dose constraints, the patient will receive 66 Gy or lower according to the normal tissue tolerance (see below). They will not be randomized, but will be followed in the trial. As such, it will be clear which proportion of patients can receive an integrated boost and what the outcome is when dose-escalation is not possible.

Stage IB-II patients receive radiotherapy alone, and stage III patients combined chemotherapy and radiation. The patients may have received induction chemotherapy up to two cycles before registration in this trial. The statistical calculations have been performed to deal with this patient heterogeneity.

The primary objective of this study is to determine the local progression-free survival (LPFS)at 1 year.

Secondary objectives will be

• Toxicity as a function of radiotherapy dose and volume of the tissue irradiated.
• Overall survival.
• Quality of life

Furthermore:

• PET imaging of hypoxia using [18F]HX4, single injection and then PET CT scanning two and four hours post injection.
• Dynamic Contrast-Enhanced CT imaging

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dose Escalation by Boosting Radiation Dose Within the Primary Tumor on the Basis of a Pre-treatment FDG-PET-CT Scan in Stage IB, II and III NSCLC: a Randomized Phase II Trial
• Study Start Date: May 2010
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Whole tumor boost; Patients in this arm will receive radiotherapy (66Gy) in 24 fractions of 2.75 Gy with an integrated boost to the primary tumor as a whole	Radiation: Radiotherapy; Radiotherapy
Boost 50% SUV area; Patients in this arm receive radiotherapy (66Gy) in 24 fractions of 2.75Gy with an integrated boost to the 50% SUVmax area of the primary tumor (of the pre-treatment FDG-PET-CT scan)	Radiation: Radiotherapy; Radiotherapy

Outcome Measures

Primary Outcome Measures :

1. Local progression-free survival at 1 year [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. Toxicity [ Time Frame: 1 year ]
2. Overall survival [ Time Frame: 1 year ]
3. Quality of life [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients > 18 years with any subtype of pathologically proven (biopsy or cytology), non-small cell lung cancer. The diagnosis may be established from biopsy or cytology obtained from the primary tumor and/ or from metastatic lymph nodes.
2. Minimal diameter of the primary tumor 4 cm, this to allow for boosting of sub-volumes.
3. UICC TNM Stage T2-4, N0-3, M0 disease (TNM definition see appendix 2).
4. Only stage IB-II patients who are nog candidates for surgery are study candidates.
5. Measurable disease at registration.
6. ECOG-performance status ≤ 2 (see appendix 6)
7. Lung function: FEV1 and DLCO at least 40 % of the age-adjusted normal value
8. Willing and able to give a written informed consent.
9. Patients with locoregional recurrent lung tumor following surgery or a second primary cancer (at least 3 years after treatment) are eligible, unless a pneumonectomy was performed.
10. SUVmax in the pre-treatment FDG-PET scan ≥ 5 for the primary tumor.

11. Adequate organ function, including the following:

    • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL.
    • Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (AP), aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) ≤ 3.0 x ULN (AP, AST, and ALT ≤ 5 x ULN is acceptable if liver has tumor involvement).
    • Renal: calculated creatinine clearance (CrCl) ≥ 45 ml/min based on the original weight based Cockcroft and Gault formula
12. For women: Must be surgically sterile, postmenopausal, or compliant with a highly reliable contraceptive method (failure rate <1%) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding.
13. For men: Must during chemotherapy take adequate contraceptive measures.

Exclusion Criteria:

1. Prior radiotherapy to the thorax.
2. Clinical superior vena cava syndrome, malignant pleural effusion or malignant pericardial effusion.
3. T4, specified as:Tumor growth in large blood vessels on spiral CT scan or encasement >50%
4. multiple nodules in the same or ipsilateral lobe(s).
5. Post-obstructive atelectasis or infiltration that cannot be distinguished from tumor on a CT-PET scan.
6. Patients with a diagnosis of other cancer within the last 3-years (except in situ carcinoma's and / or non-melanoma skin cancer).
7. Pregnant women, lactating women

Contacts and Locations

Locations

Belgium

University Hospital Leuven, campus Gasthuisberg

Leuven, Belgium, B-3000

Denmark

Rigshospitalet

Copenhagen, Denmark, 2100

Netherlands

MAASTRO clinic

Maastricht, Limburg, Netherlands, 6229 ET

NKI/AVL

Amsterdam, Netherlands, 1066CX

Academic Medical Centre

Amsterdam, Netherlands, 1105AZ

Sweden

Karolinska Hospital

Stockholm, Sweden

United Kingdom

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

The Netherlands Cancer Institute

European Union

Investigators

• Principal Investigator: José Belderbos, MD, PhD; NKI-AvL

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

van Diessen J, De Ruysscher D, Sonke JJ, Damen E, Sikorska K, Reymen B, van Elmpt W, Westman G, Fredberg Persson G, Dieleman E, Bjorkestrand H, Faivre-Finn C, Belderbos J. The acute and late toxicity results of a randomized phase II dose-escalation trial in non-small cell lung cancer (PET-boost trial). Radiother Oncol. 2019 Feb;131:166-173. doi: 10.1016/j.radonc.2018.09.019. Epub 2018 Oct 13.

Defraene G, La Fontaine M, van Kranen S, Reymen B, Belderbos J, Sonke JJ, De Ruysscher D. Radiation-Induced Lung Density Changes on CT Scan for NSCLC: No Impact of Dose-Escalation Level or Volume. Int J Radiat Oncol Biol Phys. 2018 Nov 1;102(3):642-650. doi: 10.1016/j.ijrobp.2018.06.038. Epub 2018 Jul 2.

van Elmpt W, Zegers CML, Reymen B, Even AJG, Dingemans AC, Oellers M, Wildberger JE, Mottaghy FM, Das M, Troost EGC, Lambin P. Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion. Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):240-248. doi: 10.1007/s00259-015-3169-4. Epub 2015 Sep 4.

• Responsible Party: The Netherlands Cancer Institute
• ClinicalTrials.gov Identifier: NCT01024829
• Other Study ID Numbers: PET Boost
• First Posted: December 3, 2009
• Last Update Posted: April 16, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by The Netherlands Cancer Institute:

Non small cell lung cancer; Inoperable; HX4

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases