Clinical trial NCT02397733: Memory Preservation of Prophylactic Cranial Irradiation With Hippocampal Avoidance (PREMER-TRIAL)
Official title: Phase III Trial Evaluating Memory Preservation of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance in Small Cell LUNG Cancer (PREMER-TRIAL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Small Cell Lung Carcinoma
Lead sponsor: Grupo de Investigación Clínica en Oncología Radioterapia
Sponsor class: OTHER
First posted: 2015-03-25
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Neurocognitive functioning (NCF) (Free and Cued Selective Reminding Test)
timeFrame: Change from baseline to 3 months
Secondary outcomes:
measure: Neurocognitive functioning (NCF) (Free and Cued Selective Reminding Test)
timeFrame: Change from baseline to 6,12 and 24 months
measure: Hippocampus brain metastases (brain magnetic resonance imaging) (MRI)
timeFrame: Change from baseline to 3, 6,12 and 24 months
measure: Hippocampus volume (brain magnetic resonance imaging) (MRI)
timeFrame: Change from baseline to 3, 6,12 and 24 months
measure: Adverse effects (according to Common Toxicity Criteria for Adverse Effects)
timeFrame: Change from baseline to 3, 6,12 and 24 months
measure: Quality of life (measured by European Organization for Research and Treatment of Cancer (EORTC) questionnaire (QLQ C-30 and QLQ BN-20)
timeFrame: Change from baseline to 3, 6,12 and 24 months
measure: Overall survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Del Mar. Radiation Oncology Department
Study officials:
affiliation: +34683375231
name: Núria Rodríguez de Dios, MD PhD
role: STUDY_CHAIR
References:
citation: Ishibashi A, Kurosaki H, Miura K, Utsumi N, Sakurai H. Influence of Modulation Factor on Treatment Plan Quality and Irradiation Time in Hippocampus-Sparing Whole-Brain Radiotherapy Using Tomotherapy. Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211045497. doi: 10.1177/15330338211045497.
citation: Rodriguez de Dios N, Counago F, Murcia-Mejia M, Rico-Oses M, Calvo-Crespo P, Samper P, Vallejo C, Luna J, Trueba I, Sotoca A, Cigarral C, Farre N, Manero RM, Duran X, Gispert JD, Sanchez-Benavides G, Rognoni T, Torrente M, Capellades J, Jimenez M, Cabada T, Blanco M, Alonso A, Martinez-San Millan J, Escribano J, Gonzalez B, Lopez-Guerra JL. Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study. J Clin Oncol. 2021 Oct 1;39(28):3118-3127. doi: 10.1200/JCO.21.00639. Epub 2021 Aug 11.
citation: Rodriguez de Dios N, Counago F, Lopez JL, Calvo P, Murcia M, Rico M, Vallejo C, Luna J, Trueba I, Cigarral C, Farre N, Manero RM, Duran X, Samper P. Treatment Design and Rationale for a Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for SCLC: PREMER Trial on Behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Radiation Oncology Group-Radiation Oncology Clinical Research Group. Clin Lung Cancer. 2018 Sep;19(5):e693-e697. doi: 10.1016/j.cllc.2018.05.003. Epub 2018 May 10.