Prophylactic brain irradiation or active magnetic resonance imaging monitoring of patients with small cell lung carcinoma (PRIMALung study)
Summary description of the study
Patients with small cell lung carcinoma are typically treated with a combination of chemotherapy and radiation therapy to the chest, and in some cases, an additional immunotherapy (medications that stimulate the body's immune system). When the carcinoma spreads to the rest of the body (metastases), the brain is affected in many cases. Although brain irradiations are recognized as a standard of care, current concerns regarding nervous system damage and the possibility of brain MRIs (magnetic resonance imaging) could make active monitoring instead of routine brain irradiations a potentially better alternative. Furthermore, there are open questions regarding the role and timing of brain irradiations with increased use of immunotherapy. The aim of this study is to find out whether active monitoring via brain MRIs can detect potential metastases in the brain earlier and lead to appropriate treatment without adversely affecting survival compared to brain irradiations when performed in the absence of brain metastases in addition to MRI monitoring. To find out whether the results of active monitoring via brain MRI are not purely coincidental, we need to compare data from patients who were actively monitored via brain MRI with those of patients who received prophylactic brain irradiations. Therefore, study participants will be randomly assigned to one of two groups. One group will receive daily prophylactic brain irradiations for approximately 2 weeks and will then be actively monitored via brain MRIs for up to 2 years. The other group will be actively monitored exclusively via brain MRIs for up to 2 years.
(BASEC)
Intervention under investigation
Study arm with active monitoring: MRI of the brain within 28 days prior to randomization and after 3, 6, 9, 12, 18, and 24 months. For patients who develop brain metastases, treatment of the brain metastases with radiation therapy is recommended. The techniques used to treat brain metastases, such as whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS), will be determined at the discretion of the treating physician and must be recorded. Immunotherapy may also be continued during the study according to local standard practice. Treatment arm: Prophylactic brain irradiation is administered at a dose of 25 Gy in 10 fractions to the entire brain. A hippocampus-sparing PCI is permitted and may become mandatory depending on the results of ongoing studies. Patients must undergo an MRI of the brain within 28 days prior to randomization and after 3, 6, 9, 12, 18, and 24 months. For patients who develop brain metastases, treatment of the brain metastases with radiation therapy is recommended. The techniques used to treat brain metastases, such as WBRT or SRS, will be determined at the discretion of the treating physician and must be recorded. During participation in the study, immunotherapy may be continued according to local standard practice during the PCI. However, it is recommended that PCI and immunotherapy not be administered simultaneously, so PCI should be performed between two doses of immunotherapy.
(BASEC)
Disease under investigation
small cell lung carcinoma
(BASEC)
Age >= 18 years Histologically/cytologically confirmed diagnosis of SCLC Limited and extensive stage - LS-SCLC: Stage I-III (T any, N any, M0, according to UICC TNM classification V8.0), which can be safely treated with definitive radiation doses. T3–4 due to multiple lung nodules that are too extensive or a tumor/nodule volume that is too large to be included in a tolerable radiation plan are excluded. - ES-SCLC: Stage IV (T any, N any, M 1a/b) or T3–4 due to multiple lung nodules that are too extensive or a tumor/nodule volume that is too large to be included in a tolerable radiation plan. Standard therapy completed prior to randomization: - For patients with LS-SCLC, this includes a combination of 4–6 cycles of platinum-based doublet chemotherapy and either definitive thoracic radiation therapy (including SBRT for early-stage disease T1–2 N0 M0, who do not undergo surgery) or definitive surgical resection; thoracic radiation in addition to definitive surgical resection is allowed at the discretion of the treating physician but is not mandatory. - For patients with ES-SCLC, this includes 4–6 cycles of platinum-based doublet chemotherapy with or without thoracic radiation therapy. - An immunotherapy simultaneously with and/or adjuvant to standard therapy is allowed at the discretion of the treating physician. Absence of disease progression after completion of standard therapy in systemic imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of thorax/abdomen/pelvis) 42 days prior to randomization Absence of brain metastases or leptomeningeal disease after completion of standard therapy in systemic imaging (MRI of the brain) within 28 days prior to randomization Interval from day 1 of the last chemotherapy cycle to randomization of <= 16 weeks ECOG PS <= 2 Estimated creatinine clearance >= 30 ml/min, calculated using the MDRD formula For women of childbearing potential, a serum pregnancy test must be performed within 3 days prior to randomization, which must be negative. Women of childbearing potential should use appropriate contraceptive measures, as defined by the investigator, throughout the duration of radiation therapy. Nursing patients should not breastfeed prior to the first dose of radiation therapy and during the entire duration of radiation therapy. The patient is willing and able to adhere to the study protocol for the duration of the study; this includes the willingness to undergo treatment, keep scheduled visits, and complete examinations including follow-up. Prior to patient enrollment/randomization, written informed consent must be obtained in accordance with ICH/GCP and national/local regulations. (BASEC)
Exclusion criteria
Previous brain radiation therapy or whole brain radiation therapy. Note: Patients who have undergone previous stereotactic radiosurgery for benign tumors or conditions (e.g., acoustic neuroma, meningioma grade I, trigeminal neuralgia) may be considered on a case-by-case basis. A discussion with the EORTC headquarters is mandatory before randomization. Known contraindication to imaging tracers or contrast products, such as allergy or inadequate renal function. Known contraindication to MRI, such as implanted metallic devices or foreign bodies. Other active hematological or solid tumor malignancy requiring current active treatment. Any unresolved toxicities from prior therapy (e.g., chemotherapy, radiation therapy) of greater than CTCAE grade 2 (according to CTCAE V5.0) at the time of randomization. Patient with severe active comorbidities, defined as follows: - Unstable angina pectoris and/or congestive heart failure requiring hospitalization within 3 months prior to randomization - Transmural myocardial infarction within 3 months prior to randomization - Acute infection requiring treatment at the time of randomization - Acute exacerbation of chronic obstructive pulmonary disease or another acute respiratory condition that excludes study treatment at the time of randomization - Severe liver disease, defined as a diagnosis of liver disease of Child-Pugh class B or C - HIV positive with CD4 count < 200 cells/microliter. Note: HIV-positive patients are eligible, provided they are on highly active antiretroviral therapy (HAART) and have a CD4 count of ≥ 200 cells/microliter within 16 weeks prior to randomization. - Any serious comorbidities that, in the opinion of the investigator, could affect participation in the study and/or administration of treatment. - Severe neurological (including dementia and epilepsy) or psychiatric disorder requiring active treatment. Presence of psychological, familial, sociological, or geographical circumstances that could compromise compliance with the study protocol and follow-up plan; such circumstances should be discussed with the patient prior to randomization into the study. (BASEC)
Trial sites
Bern, Lausanne, St. Gallen, Zurich
(BASEC)
Sponsor
EORTC SAKK
(BASEC)
Contact
Contact Person Switzerland
European Organisation for Research and Treatment of Cancer
+3227741611
contact@cluttereortc.orgEORTC
(BASEC)
General Information
Centre Gustave Roussy
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
01.07.2022
(BASEC)
ICTRP Trial ID
NCT04790253 (ICTRP)
Official title (approved by ethics committee)
Prophylaktische Hirnbestrahlung oder aktive Magnetresonanztomografische Überwachung von Patienten mit kleinzelligem Lungenkarzinom (PRIMALung-Studie) Irradiation cérébrale prophylactique ou surveillance active à l’aide de l’imagerie par résonance magnétique du cerveau chez des patients atteints d’un cancer du poumon à petites cellules (étude PRIMALung) (BASEC)
Academic title
PRophylactic Cerebral Irradiation or Active MAgnetic Resonance Imaging Surveillance in Small-cell Lung Cancer Patients (PRIMALung Study) (ICTRP)
Public title
PRophylactic Cerebral Irradiation or Active MAgnetic Resonance Imaging Surveillance in Small-cell Lung Cancer Patients (PRIMALung Study) (ICTRP)
Disease under investigation
Extensive-stage Small-cell Lung Cancer
Limited Stage Small Cell Lung Cancer
(ICTRP)
Intervention under investigation
Radiation: Prophylactic cranial irradiation
(ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:
- Age = 18 years
- Histologically/cytologically proven diagnosis of SCLC
- Limited and extensive stage
- LS SCLC: Stage I-III (T any, N any, M0, according to UICC TNM staging v8.0) that can
be safely treated with definitive radiation doses. Excludes T3-4 due to multiple lung
nodules that are too extensive or have tumour/nodal volume that is too large to be
encompassed in a tolerable radiation plan.
- ES SCLC: Stage IV (T any, N any, M 1a/b), or T3-4 due to multiple lung nodules that
are too extensive or have tumour/nodal volume that is too large to be encompassed in a
tolerable radiation plan.
- Completed standard therapy prior to randomization:
- For patients with LS-SCLC, this includes a combination of 4-6 cycles of platinum-based
doublet chemotherapy and either definitive thoracic radiotherapy (including SBRT for
early-stage T1-2 N0 M0 disease who do not undergo surgery) or definitive surgical
resection; thoracic radiation in addition to definitive surgical resection is allowed
at the discretion of the treating physician, but is not mandated.
- For patients with ES-SCLC, this includes 4-6 cycles of platinum-based doublet
chemotherapy either with or without thoracic radiotherapy
o Immunotherapy concurrent with and/or adjuvant to standard therapy is allowed at the
discretion of the treating physician.
- Absence of progressive disease after completed standard therapy on systemic imaging
(computed tomography (CT) or magnetic resonance imaging (MRI) of Chest/Abdomen/Pelvis
and brain MRI), 28 days before randomization.
- Absence of brain metastases or leptomeningeal disease after completed standard therapy
on systemic imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of
Chest/Abdomen/Pelvis and brain MRI), within 28 days before randomization.
- Interval from day 1 of last cycle of chemotherapy to randomization of =8 weeks
- ECOG PS = 2
- Estimated creatinine clearance = 30 mL/min as calculated using the MDRD formula
- Women of child bearing potential (WOCBP) must have a negative serum pregnancy test
within 3 days prior to randomization.
Note: women of childbearing potential are defined as premenopausal females capable of
becoming pregnant (i.e. females who have had any evidence of menses in the past 12 months,
with the exception of those who had prior hysterectomy). However, women who have been
amenorrheic for 12 or more months are still considered to be of childbearing potential if
the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight,
ovarian suppression or other reasons.
- Patients Women of childbearing / reproductive potential should use adequate birth
control measures, as defined by the investigator, during the entire period of the
radiotherapy treatment study participation and for at least 30 days after the last
dose of radiotherapy. A highly effective method of birth control is defined as a
method which results in a low failure rate (i.e. less than 1% per year) when used
consistently and correctly. Such methods include:
- Combined (oestrogen and progestogen containing) hormonal contraception associated with
inhibition of ovulation (oral, intravaginal, transdermal)
- Progestogen-only hormonal contraception associated with inhibition of ovulation (oral,
injectable, implantable)
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in
relation to the duration of the clinical trial and the preferred and usual lifestyle
of the patient)
- Female subjects who are breast feeding should discontinue nursing prior to the first
dose of radiotherapy and during the entire period of the radiotherapy treatmentuntil
30 days after the administration of the last dose of radiotherapy.
- Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up
- Before patient registration/randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations.
Exclusion Criteria:
- Prior radiotherapy to the brain or whole brain radiotherapy. Note: Patients who have
undergone prior stereotactic radiosurgery for benign tumours or conditions (e.g.,
acoustic neuroma, grade I meningioma, trigeminal neuralgia) may be considered on a
case-by-case basis. Discussion with EORTC Headquarters is mandatory, before the
randomization.
- Known contraindication to imaging tracer or any product of contrast media, such as
allergy or insufficient renal function. Known contraindication to MRI, such as
implanted metal devices or foreign bodies.
- Other active hematologic or solid tumour malignancy requiring current active
treatment.
- Any unresolved toxicities from prior therapy (e.g., chemotherapy, radiotherapy)
greater than CTCAE grade 2 (according to CTCAE v5.0) at the time of randomization.
- Patient with severe active comorbidities, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within 6
months prior to randomization
- Transmural myocardial infarction within 6 months prior to randomization
- Acute infection requiring treatment at the time of randomization
- Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness
precluding study therapy at the time of randomization
- Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic
disease
- HIV positive with CD4 count < 200 cells/microliter. Note: patients who are HIV
positive are eligible, provided they are under treatment with highly active
antiretroviral therapy (HAART) and have a CD4 count = 200 cells/microliter within 16
weeks prior to randomization.
- Any severe comorbidity that in the opinion of the Investigator might hamper the
participation to the study and/or the treatment administration.
- Severe neurological (including dementia and epilepsy) or psychiatric disorder
requiring active treatment.
- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions
should be discussed with (ICTRP)
not available
Primary and secondary end points
Overall survival
(ICTRP)
Safety profiling
cognitive failure free survival
Quality of Life
(ICTRP)
Registration date
05.03.2021 (ICTRP)
Incorporation of the first participant
27.10.2022 (ICTRP)
Secondary sponsors
UNICANCER
(ICTRP)
Additional contacts
Antonin Levy, MD, Centre Gustave Roussy (ICTRP)
Secondary trial IDs
EORTC-1901-LCG (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04790253 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available