Description:
The patients carrying a complicated primary lung cancer brain metastases die in less than 3
months of delay disease in the absence of treatment. The median survival of these patients is
approximately six months when the treatment associated with radiotherapy chemotherapy based
on cisplatin is now the standard treatment. In most studies the patients die of their brain
disease in one case only two, so it is likely that some patients do not require brain
irradiation (prognosis in this case is linked to extra-cerebral disease ). The benefits for
patients in group B (without systematic irradiation) are not to suffer the side effects of
this radiation. The risks are in the same group to see brain metastases become symptomatic.
The role of cerebral radiotherapy in the patients treated with chemotherapy is unclear:
should all patients be irradiated systematically (since the "reference" treatment is involved
and with the aim of obtaining better control of the brain lesions and maintaining a better
neurological status) or should only the patients showing cerebral progression be irradiated
(avoidance of possibly useless brain radiotherapy and its side effects). The aim of this
study is to better determine the position of cerebral radiotherapy in this context.
Main objective:
determine whether there is a difference in terms of progression-free survival between a
therapeutic strategy with initial systematic brain radiotherapy followed by chemotherapy
cis-platine/alimta + / - Bevacizumab and strategy with an initial chemotherapy
cis-platine/alimta + / - Bevacizumab associated with brain radiotherapy only in cases of
cerebral progression in patients with NSCLC with asymptomatic brain metastases
Title
- Brief Title: Therapeutic Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Brain Metastases
- Official Title: Multicentric, Randomized, Phase III Trial Comparing 2 Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Asymptomatic Brain Metastases
Clinical Trial IDs
- ORG STUDY ID:
METAL 2
- NCT ID:
NCT02162537
Conditions
- Non-small Cell Lung Cancer Metastatic
- Non-small Cell Lung Cancer
- Adenocarcinoma of Lung Metastatic to Brain
- Cerebral Metastases
Interventions
| Drug | Synonyms | Arms |
|---|
| Cisplatin | Cisplatine | Arm A (standard arm) |
| Pemetrexed | Alimta | Arm A (standard arm) |
| Bevacizumab | Avastin | Arm A (standard arm) |
Purpose
The patients carrying a complicated primary lung cancer brain metastases die in less than 3
months of delay disease in the absence of treatment. The median survival of these patients is
approximately six months when the treatment associated with radiotherapy chemotherapy based
on cisplatin is now the standard treatment. In most studies the patients die of their brain
disease in one case only two, so it is likely that some patients do not require brain
irradiation (prognosis in this case is linked to extra-cerebral disease ). The benefits for
patients in group B (without systematic irradiation) are not to suffer the side effects of
this radiation. The risks are in the same group to see brain metastases become symptomatic.
The role of cerebral radiotherapy in the patients treated with chemotherapy is unclear:
should all patients be irradiated systematically (since the "reference" treatment is involved
and with the aim of obtaining better control of the brain lesions and maintaining a better
neurological status) or should only the patients showing cerebral progression be irradiated
(avoidance of possibly useless brain radiotherapy and its side effects). The aim of this
study is to better determine the position of cerebral radiotherapy in this context.
Main objective:
determine whether there is a difference in terms of progression-free survival between a
therapeutic strategy with initial systematic brain radiotherapy followed by chemotherapy
cis-platine/alimta + / - Bevacizumab and strategy with an initial chemotherapy
cis-platine/alimta + / - Bevacizumab associated with brain radiotherapy only in cases of
cerebral progression in patients with NSCLC with asymptomatic brain metastases
Detailed Description
This is a trial comparing two strategies with the aim to determine the best place for
cerebral radiotherapy (initially or only systematic progression).
Arm A: Initial cerebral radiotherapy and chemotherapy, standard arm Arm B: Chemotherapy and
Radiotherapy brain if clinical or radiological cerebral progression , experimental arm (The
chemotherapy treatments are standard treatments using drugs with authorization in this
indication)
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A (standard arm) | Other | Arm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) | - Cisplatin
- Pemetrexed
- Bevacizumab
|
| Arm B (experimental arm) | Other | Arm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain | - Cisplatin
- Pemetrexed
- Bevacizumab
|
Eligibility Criteria
Inclusion Criteria:
1. Patients with histologically or cytologically proven non-epidermoid, non-small cell
lung cancer, non-EGFR (Epidermal Growth Factor Receptor)-mutated (or mutation test
impracticable).
2. Patients with brain metastasis/metastases without neurosurgical indication.
3. Asymptomatic patients (without treatment or with stable steroids or antiepileptic
treatments for ≥ 5 days prior to obtaining the baseline MRI of the brain, and ≥ 5 days
prior to first dose of study treatment (Cycle 1, Day 1).
4. At least one lesion measurable according to the RECIST (Response Evaluation Criteria
in Solid Tumors) criteria.
5. ECOG (Eastern Cooperative Oncology Group) Performance Status 0 - 1
6. No previous chemotherapy for this cancer, apart from adjunctive chemotherapy more than
18 months ago.
7. Prior surgery is authorized in case of documented recurrence or progression.
8. Adequate biological functions (hematologic, platelets, hemoglobin, hepatic function,
alkaline phosphatases, ASAT (Aspartate transaminase) and ALAT (Alanine
Aminotransferase); creatinine clearance).
9. For women: Effective contraception for women of childbearing age during treatment and
for 6 months following treatment.
For men: They must be surgically sterile or accept the use of effective contraception
until 6 months after the treatment period.
10. Patients of more than 18 years of age.
11. Estimated survival of at least 12 weeks.
12. Consent signed by the patient
Exclusion Criteria:
1. Patients presenting with a brain lesion eligible for curative treatment
(neurosurgical).
2. Symptomatic brain metastasis/metastases in spite of symptomatic treatment.
3. Epidermoid carcinoma.
4. Con indication of Bevacizumab is furthermore
5. Patients presenting with a brain lesion eligible for curative treatment (neurosurgery
or radiosurgery).
6. Symptomatic brain metastasis/metastases in spite of symptomatic treatment.
7. Epidermoid carcinoma.
8. Cons indication of Bevacizumab
9. Inability to take the folic acid or vitamin B12 vitamin supplementation or the
dexamethasone premedication (or any equivalent corticosteroid), or any inability to
comply with the study procedures.
10. History of cancer, with the exception of cervical cancer in situ, skin cancer other
than melanoma, adequately treated low-grade prostatic cancer (Gleason score <6),
unless this cancer was diagnosed and treated more than 5 years ago without any signs
of recurrence.
11. Patients presenting with a systemic disorder which, in the investigator's opinion,
compromises their participation in the study for reasons related to treatment safety
or compliance.
12. Patients incapable of discontinuing their aspirin treatment when the dose is > 1300
mg/day or their non-steroidal anti-inflammatory treatment two days before the day, on
the day and two days the day of administration of pemetrexed (Alimta).
13. Patients presenting with a 3rd sector (pleural effusion, ascites) which is clinically
detectable and uncontrollable by simple measures of the evacuatory puncture type or
other treatment before inclusion in the study.
14. Patients presenting with neuropathy of grade > 2 according to the criteria of CTC
(Common toxicity Criteria) v3.0.
15. Patients whose foreseeable compliance or geographical distance renders monitoring
difficult.
16. Pregnant or breast-feeding women.
17. Significant weight loss (≥ 10%) during the 6 weeks preceding inclusion in the study.
18. Vaccination against yellow fever within 30 days preceding inclusion in the study.
19. Cons-indication to taking steroids
20. Persons deprived of their liberty as a result of a judicial or administrative decision
21. Concomitant participation in another trial
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | To compare the progression-free survival rate in both arms |
| Time Frame: | From date of the randomization until the date of first detection of progression, or until the date of death, assessed up to up to approximately 90 months |
| Safety Issue: | |
| Description: | Whether there is a difference in terms of progression-free survival between a therapeutic strategy with initial brain radiotherapy followed by systematic chemotherapy with cis-platinum / alimta and a strategy with initial chemotherapy with cis-platinum / alimta with brain radiotherapy only if brain progression in patients with non-small cell lung cancer with brain metastases asymptomatic. |
Secondary Outcome Measures
| Measure: | Overall survival |
| Time Frame: | From the date of randomization until the date of patient death, assessed up to 90 months |
| Safety Issue: | |
| Description: | After 4 cycles of chemotherapy with platinum salt-pemetrexed (with or without bevacizumab) possibly followed, in case of control of the disease and if the patient's condition allows, by pemetrexed (alone or with bevacizumab if the latter was part of the initial treatment) as maintenance treatment until progression. |
| Measure: | Disease control rate (response + stability) |
| Time Frame: | Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months |
| Safety Issue: | |
| Description: | Repeat examinations to assess the measurable lesions or initials and examination necessary to confirm the appearance of a new lesion in case of clinical suspicion of disease progression (minimum CT scan and MRI).The radiological treatment response will be measured according to the RECIST 1.1 criteria |
| Measure: | Tolerance of treatment |
| Time Frame: | Every 3 weeks, up to approximately 24 months |
| Safety Issue: | |
| Description: | The safety of the induction combination of cisplatin or carboplatin plus pemetrexed (Alimta®) +/- bevacizumab, the maintenance treatment with pemetrexed (Alimta®) +/- bevacizumab and the pancerebral radiotherapy will be assessed based on the CTC toxicity criteria v3.0. |
| Measure: | Quality of life assessment |
| Time Frame: | Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months |
| Safety Issue: | |
| Description: | The quality of life assessment measurement will be performed by self-questionnaire. The EURO-QOL questionnaire will be used. |
| Measure: | Neurological assessment |
| Time Frame: | Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months |
| Safety Issue: | |
| Description: | The neurological assessment measurement will be performed by self-questionnaire. The MOCA questionnaires will be used. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Centre Hospitalier Intercommunal Creteil |
Trial Keywords
- Strategy
- Radiotherapy
- Chemotherapy
- Cisplatin
Last Updated
February 1, 2019
