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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

Phase 2
18 Years
Open (Enrolling)

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Trial Information

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

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


- 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

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

3. UICC 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

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. Tumor growth in large blood vessels on spiral CT scan (encasement is eligible).

4. T4 because of 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. Patients taking non-steroidal anti-inflammatory drugs (NSAID) or acetylsalicylic acid
may not receive pemetrexed.

8. Pregnant women, lactating women

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Local progression-free survival at 1 year

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

José Belderbos, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:



Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:

PET Boost



Start Date:

May 2010

Completion Date:

August 2014

Related Keywords:

  • Non small cell lung cancer
  • Inoperable
  • HX4
  • Carcinoma, Non-Small-Cell Lung