Small-Cell Lung CancerNCT02058056
Early Hippocampal Avoidance Prophylactic Cranial Irradiation in Patients With LD SCLC
A study testing Irradiation: HA-PCI in people with Small-Cell Lung Cancer, run by Swiss Cancer Institute at 8 sites in Switzerland.
Trial summary
The main objective of this trial is to assess NCF after early HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Small-Cell Lung Cancer
- What is being tested?
- Irradiation: HA-PCI
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 8 sitesSwitzerland
- Study dates
- 11 Jul 2014to 3 Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed cytologically or histologically confirmed diagnosis of SCLC within 6 weeks before registration.
- Proven LD SCLC (CT thorax, abdomen, and bone scan (or PET/CT only) and brain MRI within 6 weeks before registration) according to the TNM classification version 7 that can be encompassed within a radical radiation port
- Only patients assessed by an interdisciplinary tumor board should be declared eligible taking into account eligibility for curative tRT and CHT according to NCCN Guidelines version 2.2014
- Karnofsky Index ≥ 60%
- Age at registration 18 to 75 years
- Normal bone marrow function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
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- Calculated creatinine clearance ≥ 60 mL/min is required if chemotherapy with cisplatin is scheduled. If cisplatin has to be replaced by carboplatin a creatinine clearance ≥ 50 mL/min is required
- Normal liver function: bilirubin ≤ 1 x ULN, AST and ALT ≤1.5 x ULN
- Fluency in either German, French or Italian
- Women are not breastfeeding. Women with child-bearing potential are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 6 months thereafter. A negative pregnancy test before inclusion (within 7 days) into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and during 6 months thereafter.
- Baseline QoL questionnaires FACT-Br and GHQ-12 have been completed within 14 days before registration
- Baseline NCF assessments have been completed within 14 days before registration:
- HVLT-R
- COWAT
- TMT A
- TMT B
- Patient must give written informed consent before registration
Who cannot join
- Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
- History of CNS metastases
- Prior brain RT
- History of RT to the thorax
- Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out QoL forms, participating in assessing NCF testing or interfering with compliance for oral drug intake.
- Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry.
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- Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes).
- Any concomitant drugs contraindicated for use with the treatment drugs according to the approved product information.
- History of cerebrovascular disease or epilepsy requiring continuous treatment
- Symptomatic cardiac disease or a history of myocardial infarction within the previous 3 months
- Any psychological, familial or sociological/geographical conditions potentially hampering compliance with the study protocol and follow-up schedule
- Legal incapacity or limited legal capacity
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Switzerland8 sites
Universitätsspital Basel
Basel, CH-4031
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, 6500
Inselspital Bern
Bern, CH-3010
Kantonsspital Graubuenden
Chur, 7000
Hopital Fribourgeois
Fribourg, 1708
Hopitaux Universitaires de Geneve
Geneva, 1211
Kantonsspital - St. Gallen
Sankt Gallen, CH-9007
Kantonsspital Winterthur
Winterthur, CH-8400
About this study
Official title: Early Prophylactic Cranial Irradiation With Hippocampal Avoidance in Patients With Limited Disease Small-cell Lung Cancer. A Multicenter Phase II Trial
The main objective of this trial is to assess NCF after early HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC.
Read the detailed description
About 15% of all lung cancers are small cell lung cancer (SCLC). SCLC is a high-grade, neuroendocrine carcinoma of the lung. Limited disease (LD) SCLC is confined to the hemithorax of origin, the mediastinum, or the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. About 30% of all SCLC are LD at diagnosis. The median overall survival (OS) in LD SCLC is approximately 20 months, with an expected 5-year survival of less than 15%.
SCLC is characterized by rapid growth and early dissemination. The standard treatment of LD SCLC involves multimodality therapy with concurrent thoracic radiotherapy (tRT) and chemotherapy (CHT) with cisplatin and etoposide.
Recurrence in the brain is usually the primary site of treatment failure in SCLC and is associated with significant morbidity; and consequently often the cause of death. Occult early dissemination of SCLC has frequently occurred prior to the time of diagnosis. In patients with brain metastasis two randomized trials showed an overall 5-year rate of brain metastasis of 59% without prophylactic cranial irradiation (PCI) compared to 43% with PCI. However the rate of brain metastasis with PCI is still very high.
About 50% of patients with SCLC will develop brain metastases some time during the course of their disease. Therefore PCI is recommended in case of good response to CHT and tRT. PCI has shown to improve overall survival in patients with LD who have achieved a complete or partial remission after initial chemoradiotherapy. CHT might achieve insufficient drug levels in the brain. Therefore, an up-front PCI could treat occult brain metastases at a preclinical state and may increase the permeability of the blood-brain barrier for CHT products.
When evaluating PCI it is important to weigh the reduced incidence of brain metastases against the potential risk of deficits resulting from the treatment itself, including deteriorations in neurocognitive functions (NCF) or quality of life (QoL).
A possibility to reduce long-term neurocognitive effects due to PCI is the sparing of the hippocampus. Recent technological advancements in radiation oncology delivery enable the avoidance of the hippocampus. A PCI with hippocampus avoidance (HA-PCI) can reduce memory loss due to radiation.
Prospective neurocognitive testing has been increasingly used in trials for patients with CNS tumors and in patients with brain metastases in order to determine the risks versus benefits of different treatment approaches. For this trial, the choice for NCF assessments follows the recommendation provided by Meyers and Brown (2006). This neurocognitive battery for the use in multinational drug trials with neurocognitive endpoints consists of four standardized psychometric instruments, i.e. the Hopkins Verbal Learning Test, the Controlled Oral Word Association Test (COWAT) and the Trail Making Part A and Part B (TMT A/B). These tests have been shown to be sensitive to the neurotoxic effects of cancer treatment in clinical trials and cover several cognitive functions (memory, verbal fluency, visual-motor speed, executive function). In addition, published normative data are available that take into account age, and where appropriate, education and sex. To minimize the effects of repeated administration alternate forms can be used and test administration is highly standardized. The same battery of tests has been used in trials conducted by the Radiation Therapy Oncology Group (RTOG) (e.g. Wolfson 2011), and one or several of these three tests were applied in most of the studies mentioned above. Using the same tests across trials is important in order to be able to compare results of different trials. It has been shown that performing a cognitive test battery consisting of five cognitive tests (and a QoL assessment) in a multi-site trial and cooperative group setting (i.e. a RTOG trial) in patients with brain metastases is feasible.
NCF can be affected by a number of factors such as the volume of brain metastases, disease progression, other treatments (e.g. surgery, chemo- or endocrine therapy), medications and psychological factors such as anxiety and distress. These factors should be considered when evaluating the actual neurocognitive effect of concomitant CHT, tRT and PCI.
Rationale for performing the trial PCI is part of the standard treatment of LD SCLC as the rate of developing brain metastases is very high and PCI has shown to increase overall survival. PCI is given to patients presenting a good response to CHT and tRT. However the overall 5-year rate of brain metastasis with PCI is still very high.
As long as safety data are lacking on PCI administered concurrently with CHT and tRT, PCI is given after the end of CHT in the clinical practice. Therefore the aim of this phase II trial is to evaluate to what extent early HA-PCI given concomitant to CHT and tRT impairs NCF and whether this neurotoxicity can be considered acceptable to evaluate this question in a phase III trial.
- Conditions
- Small-Cell Lung Cancer
- Being tested
- Irradiation: HA-PCI
- Keywords
- Early prophylactic, cranial irradiation, hippocampal avoidance, limited disease small-cell lung cancer
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irradiation: HA-PCIRadiation
25 Gy in 10 daily factions, five times a week
| Study group | Role | What they receive |
|---|---|---|
| Experimental: HA-PCI treatment | Experimental | Irradiation HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC Receives: Radiation: Irradiation: HA-PCI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurocognitive functioning (NCF)
NCF at 6 months after end of HA-PCI treatment measured by Hopkins Verbal Learning Test Revised (HVLT-R), Controlled Oral Word Association (COWAT) and Trail Making Test Part A and B (TMT A/B). A neurocognitive decline is defined as a decrease of one standard error of measurement (SEM) in any of the four NCF tests.
Measured: at 6 months
Secondary outcomes (6)
Brain metastasis free survival (BMFS)
Measured: At 6 months and 12 months.
Adverse events according to NCI CTCAE version 4.0
Measured: Until 1 year after the end of HA-PCI treatment.
Neurotoxicity
Neurotoxicity according to NCI CTCAE version 4.0
Measured: Until 1 year after HA-PCI treatment.
Individual tests for each cognitive domain (memory, verbal fluency, visual motor speed, executive function).
Measured: At 6 weeks, 6 and 12 months after the end of HA-PCI treatment.
Overall survival (OS)
Measured: From time of registration (expected average of 20 months)
Quality of Life (QoL) measured by functional assessment of cancer therapy-brain (FACT-Br) and general health questionnaire (GHQ-12)
Measured: At 6 weeks, 6 and 12 months after the end of HA-PCI treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2014 (estimated)
- Study start11 Jul 2014
- Primary completion7 Jun 2018
- Study completion3 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small-Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francesca Caparrotti, MD, Study chair, Hôpitaux Universitaires de Genève, Genève
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02058056
- Sponsor's protocol ID
- SAKK 15/12
- Status last verified
- Jan 2020
- First submitted
- 4 Feb 2014
- Last updated
- 29 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Prophylactic Cranial Irradiation With Hippocampal Avoidance in Patients With Limited Disease Small-cell Lung Cancer. A Multicenter Phase II Trial
- ClinicalTrials.gov ID
- NCT02058056
- Acronym / sponsor ID
- SAKK 15/12
- Conditions
- Small-Cell Lung Cancer
- Keywords
- Early prophylactic, cranial irradiation, hippocampal avoidance, limited disease small-cell lung cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Swiss Cancer InstituteUniversity, hospital or other
- Study start
- 11 Jul 2014 (actual)
- Primary completion
- 7 Jun 2018 (actual)
- Study completion
- 3 Dec 2018 (actual)
- First posted
- 7 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of this trial is to assess NCF after early HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC.
Detailed description
About 15% of all lung cancers are small cell lung cancer (SCLC). SCLC is a high-grade, neuroendocrine carcinoma of the lung. Limited disease (LD) SCLC is confined to the hemithorax of origin, the mediastinum, or the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. About 30% of all SCLC are LD at diagnosis. The median overall survival (OS) in LD SCLC is approximately 20 months, with an expected 5-year survival of less than 15%.
SCLC is characterized by rapid growth and early dissemination. The standard treatment of LD SCLC involves multimodality therapy with concurrent thoracic radiotherapy (tRT) and chemotherapy (CHT) with cisplatin and etoposide.
Recurrence in the brain is usually the primary site of treatment failure in SCLC and is associated with significant morbidity; and consequently often the cause of death. Occult early dissemination of SCLC has frequently occurred prior to the time of diagnosis. In patients with brain metastasis two randomized trials showed an overall 5-year rate of brain metastasis of 59% without prophylactic cranial irradiation (PCI) compared to 43% with PCI. However the rate of brain metastasis with PCI is still very high.
About 50% of patients with SCLC will develop brain metastases some time during the course of their disease. Therefore PCI is recommended in case of good response to CHT and tRT. PCI has shown to improve overall survival in patients with LD who have achieved a complete or partial remission after initial chemoradiotherapy. CHT might achieve insufficient drug levels in the brain. Therefore, an up-front PCI could treat occult brain metastases at a preclinical state and may increase the permeability of the blood-brain barrier for CHT products.
When evaluating PCI it is important to weigh the reduced incidence of brain metastases against the potential risk of deficits resulting from the treatment itself, including deteriorations in neurocognitive functions (NCF) or quality of life (QoL).
A possibility to reduce long-term neurocognitive effects due to PCI is the sparing of the hippocampus. Recent technological advancements in radiation oncology delivery enable the avoidance of the hippocampus. A PCI with hippocampus avoidance (HA-PCI) can reduce memory loss due to radiation.
Prospective neurocognitive testing has been increasingly used in trials for patients with CNS tumors and in patients with brain metastases in order to determine the risks versus benefits of different treatment approaches. For this trial, the choice for NCF assessments follows the recommendation provided by Meyers and Brown (2006). This neurocognitive battery for the use in multinational drug trials with neurocognitive endpoints consists of four standardized psychometric instruments, i.e. the Hopkins Verbal Learning Test, the Controlled Oral Word Association Test (COWAT) and the Trail Making Part A and Part B (TMT A/B). These tests have been shown to be sensitive to the neurotoxic effects of cancer treatment in clinical trials and cover several cognitive functions (memory, verbal fluency, visual-motor speed, executive function). In addition, published normative data are available that take into account age, and where appropriate, education and sex. To minimize the effects of repeated administration alternate forms can be used and test administration is highly standardized. The same battery of tests has been used in trials conducted by the Radiation Therapy Oncology Group (RTOG) (e.g. Wolfson 2011), and one or several of these three tests were applied in most of the studies mentioned above. Using the same tests across trials is important in order to be able to compare results of different trials. It has been shown that performing a cognitive test battery consisting of five cognitive tests (and a QoL assessment) in a multi-site trial and cooperative group setting (i.e. a RTOG trial) in patients with brain metastases is feasible.
NCF can be affected by a number of factors such as the volume of brain metastases, disease progression, other treatments (e.g. surgery, chemo- or endocrine therapy), medications and psychological factors such as anxiety and distress. These factors should be considered when evaluating the actual neurocognitive effect of concomitant CHT, tRT and PCI.
Rationale for performing the trial PCI is part of the standard treatment of LD SCLC as the rate of developing brain metastases is very high and PCI has shown to increase overall survival. PCI is given to patients presenting a good response to CHT and tRT. However the overall 5-year rate of brain metastasis with PCI is still very high.
As long as safety data are lacking on PCI administered concurrently with CHT and tRT, PCI is given after the end of CHT in the clinical practice. Therefore the aim of this phase II trial is to evaluate to what extent early HA-PCI given concomitant to CHT and tRT impairs NCF and whether this neurotoxicity can be considered acceptable to evaluate this question in a phase III trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: HA-PCI treatment | Experimental | Radiation: Irradiation: HA-PCIIrradiation HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Newly diagnosed cytologically or histologically confirmed diagnosis of SCLC within 6 weeks before registration.
- Proven LD SCLC (CT thorax, abdomen, and bone scan (or PET/CT only) and brain MRI within 6 weeks before registration) according to the TNM classification version 7 that can be encompassed within a radical radiation port
- Only patients assessed by an interdisciplinary tumor board should be declared eligible taking into account eligibility for curative tRT and CHT according to NCCN Guidelines version 2.2014
- Karnofsky Index ≥ 60%
- Age at registration 18 to 75 years
Key exclusion criteria (12 listed)
- Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
- History of CNS metastases
- Prior brain RT
- History of RT to the thorax
- Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out QoL forms, participating in assessing NCF testing or interfering with compliance for oral drug intake.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Irradiation: HA-PCI25 Gy in 10 daily factions, five times a week | Radiation | Experimental: HA-PCI treatment |
Primary outcome
Neurocognitive functioning (NCF)
Time frame: at 6 months
NCF at 6 months after end of HA-PCI treatment measured by Hopkins Verbal Learning Test Revised (HVLT-R), Controlled Oral Word Association (COWAT) and Trail Making Test Part A and B (TMT A/B). A neurocognitive decline is defined as a decrease of one standard error of measurement (SEM) in any of the four NCF tests.
6 secondary outcomes
Brain metastasis free survival (BMFS)
Time frame: At 6 months and 12 months.
Adverse events according to NCI CTCAE version 4.0
Time frame: Until 1 year after the end of HA-PCI treatment.
Neurotoxicity
Time frame: Until 1 year after HA-PCI treatment.
Individual tests for each cognitive domain (memory, verbal fluency, visual motor speed, executive function).
Time frame: At 6 weeks, 6 and 12 months after the end of HA-PCI treatment.
Overall survival (OS)
Time frame: From time of registration (expected average of 20 months)
Quality of Life (QoL) measured by functional assessment of cancer therapy-brain (FACT-Br) and general health questionnaire (GHQ-12)
Time frame: At 6 weeks, 6 and 12 months after the end of HA-PCI treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesca Caparrotti, MD study chair
Hôpitaux Universitaires de Genève, Genève
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Irradiation: HA-PCI in people with Small-Cell Lung Cancer, run by Swiss Cancer Institute at 8 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurocognitive functioning (NCF) (time frame: at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2020.