Testování trametinibu jako potenciální cílené léčby u rakoviny s genetickými změnami NF1 (MATCH-Subprotocol S1)
Podprotokol léčby MATCH S1: Studie fáze II s trametinibem u pacientů s nádory s mutacemi NF1
This phase II MATCH treatment trial identifies the effects of trametinib in patients whose cancer has a has a genetic change called NF1 mutation. Trametinib blocks proteins called MEK1 and MEK2, which may be needed for cancer cell growth when an NF1 mutation is present. Researchers hope to learn if trametinib will shrink this type of cancer or stop its growth.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
PRIMARY OBJECTIVE:
I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.
OUTLINE:
Patients receive trametinib dimethyl sulfoxide orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Pennsylvania
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Philadelphia, Pennsylvania, Spojené státy, 19103
- ECOG-ACRIN Cancer Research Group
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
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Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
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Patients must have deleterious inactivating mutations of NF-1, or another aberration, as determined via the MATCH Master Protocol
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Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria:
- Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
- Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
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Patients must have an echocardiogram (ECHO) or a nuclear study (multigated acquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible
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Patients who previously received monoclonal antibody therapy (eg. ipilimumab, nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib
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Patients with glioblastoma must have histologically or radiographically confirmed recurrent or progressive World Health Organization (WHO) grade 4 glioma (glioblastoma)
- NOTE: All baseline and post-baseline disease assessments must be performed using contrast-enhanced cranial magnetic resonance spectroscopy (MRI) or contrast-enhanced computed tomography (CT) for subjects who cannot have MRI performed
Exclusion Criteria:
- Patients with a history of interstitial lung disease or pneumonitis are excluded
- Patients must not have known hypersensitivity to trametinib or compounds of similar chemical or biologic composition or to dimethyl sulfoxide (DMSO).
- Patients must not have a history or current evidence/risk of retinal vein occlusion (RVO). An eye exam is required at baseline
- Patients who previously received MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and pimasertib) will be excluded
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Treatment (trametinib)
Patients receive trametinib dimethyl sulfoxide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Given PO
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Objective Response Rate (ORR)
Časové okno: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
|
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR. |
Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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6-month Progression-free Survival (PFS) Rate
Časové okno: Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
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Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point. |
Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
|
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Progression Free Survival (PFS)
Časové okno: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
|
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. |
Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Jason J Luke, ECOG-ACRIN Cancer Research Group
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Cévní onemocnění
- Kardiovaskulární choroby
- Novotvary podle místa
- Novotvary
- Onemocnění imunitního systému
- Novotvary podle histologického typu
- Hematologická onemocnění
- Lymfatická onemocnění
- Lymfoproliferativní poruchy
- Imunoproliferativní poruchy
- Novotvary, plazmatické buňky
- Hemostatické poruchy
- Paraproteinémie
- Poruchy krevních bílkovin
- Hemoragické poruchy
- Hemická a lymfatická onemocnění
- Hematologické novotvary
- Lymfom
- Mnohočetný myelom
- trametinib
Další identifikační čísla studie
- NCI-2020-03343
- U10CA180820 (Grant/smlouva NIH USA)
- U24CA196172 (Grant/smlouva NIH USA)
- NCI-2020-03343 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- EAY131-S1 (Jiný identifikátor: CTEP)
- EAY131-S1 (Jiný identifikátor: ECOG-ACRIN Cancer Research Group)
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