Memory Preservation of Prophylactic Cranial Irradiation With Hippocampal Avoidance (PREMER-TRIAL)

Study Overview
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Brief Summary
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The main objective of this study i sto evaluate the impact of prophylactic cranial irradiation (PCI) with hippocampal avoidance in the neurocognitive function and quality of life of small cell lung cancer patients. In addition, the trial assesses the potential changes in hippocampal volumetry due to cranial irradiation using magnetic resonance imaging.

Detailed Description
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Prophylactic cranial irradiation (PCI) has become a standard of care for selected patients with limited and extensive stage small cell lung cancer (SCLC) who have shown benefit after chemotherapy with or without thoracic radiotherapy. Because hippocampal involvement by metastatic disease is rare, and because preclinical and clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy may play a role in radiation-induced neurocognitive decline, sparing of the hippocampus during the administration of PCI should result in lower rates of memory loss. Previous studies have demonstrated the dosimetric capabilities of intensity modulated radiation therapy (IMRT) to conformably avoid the hippocampus without detriment to the radiation dose the remaining brain receives. The main objective of this trial is compare neurocognitive functioning following hippocampal avoidance PCI to standard PCI treatment measured by Free and Cued Selective Reminding Test (FCSRT). The FCSRT measures verbal learning and memory. The FCSRT emphasizes encoding specificity during learning and recall. One of the secondary objectives of this trial is to test the hypothesis that the lowered neurocognitive function of the patients is due to a substantial reduction in hippocampal volume in magnetic resonance imaging (MRI). Others objectives are to evaluate quality of life (QoL) and the rate of metastases in the hippocampus.

Official Title
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Phase III Trial Evaluating Memory Preservation of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance in Small Cell LUNG Cancer (PREMER-TRIAL)

Conditions
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Small Cell Lung Carcinoma

Intervention / Treatment
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* Radiation: Prophylactic cranial irradiation (PCI)
* Radiation: Hippocampal avoidance PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New diagnosed cytological or histologically confirmed Small cell lung carcinoma (stage I-IV) candidate for PCI, for example, without progressive disease after chemo-radiotherapy in stage I-III or after response after chemotherapy in stage IV Performance status ≤ 1 Negative MRI of the brain within one month before protocol entry Patient must give written informed consent before registration Exclusion Criteria: Prior radiotherapy to the brain History of brain metastases Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prophylactic cranial irradiation (PCI)<br>Radiation. Prophylactic cranial irradiation : 25 Gy in 10 daily fractions, five times a week | Radiation: Prophylactic cranial irradiation (PCI)<br>* Prophylactic cranial irradiation (PCI): 25 Gy in 10 daily fractions, five times a week<br>|
| Experimental: Hippocampal avoidance PCI<br>Hippocampal avoidance prophylactic cranial irradiation. 25 Gy in 10 daily fractions, five times a week | Radiation: Hippocampal avoidance PCI<br>* Hippocampal avoidance prophylactic cranial irradiation 25 Gy in 10 daily fractions, five times a week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive functioning (NCF) (Free and Cued Selective Reminding Test) | Free and Cued Selective Reminding Test (FCSRT) evaluated at baseline and 3 months after radiation | Change from baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive functioning (NCF) (Free and Cued Selective Reminding Test) | Free and Cued Selective Reminding Test (FCSRT) evaluated at baseline and 6,12 and 24 months after radiation | Change from baseline to 6,12 and 24 months | 
| Hippocampus brain metastases (brain magnetic resonance imaging) (MRI) | Evaluation of hippocampus brain metastases at 3, 6, 12 and 24 months after radiation | Change from baseline to 3, 6,12 and 24 months | 
| Hippocampus volume (brain magnetic resonance imaging) (MRI) | Evaluation of hippocampus volume at 3, 6, 12 and 24 months after radiation | Change from baseline to 3, 6,12 and 24 months | 
| Adverse effects (according to Common Toxicity Criteria for Adverse Effects) | Evaluation of adverse effects according to Common Toxicity Criteria for Adverse Effects (NCI-CTCAE) version 4.0 at 3, 6, 12 and 24 months after radiation | Change from baseline to 3, 6,12 and 24 months | 
| Quality of life (measured by European Organization for Research and Treatment of Cancer (EORTC) questionnaire (QLQ C-30 and QLQ BN-20) | Evaluation of Quality of Life (QoL) measured by European Organization for Research and Treatment of Cancer (EORTC) questionnaire (QLQ C-30 and QLQ BN-20) | Change from baseline to 3, 6,12 and 24 months | 
| Overall survival | From the start date of PCI until the date of death from any cause, or the last follow-up date whichever came first, assessed up to 60months | Up to 5 years |