Prüfung von Binimetinib als potenzielle zielgerichtete Behandlung bei Krebserkrankungen mit NRAS-genetischen Veränderungen (MATCH-Unterprotokoll Z1A)
MATCH-Behandlung Unterprotokoll Z1A: Binimetinib bei Patienten mit Tumoren (außer Melanomen) mit NRAS-Mutationen
This phase II MATCH treatment trial investigates the good and bad effects of binimetinib in patients whose cancer has a genetic change called NRAS mutation. Binimetinib blocks proteins called MEK1 and MEK2, which may be needed for cancer cell growth when an NRAS mutation is present. Researchers hope to learn if binimetinib will shrink this type of cancer or stop its growth.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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 binimetinib orally (PO) twice daily (BID) 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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
Kontakte und Standorte
Studienorte
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Pennsylvania
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Philadelphia, Pennsylvania, Vereinigte Staaten, 19103
- ECOG-ACRIN Cancer Research Group
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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 NRAS mutation in codon 12, 13, 61 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 no clinically significant abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
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Creatinine =< 1.5 mg/dL, or calculated creatinine clearance (determined as per Cockcroft-Gault) >= 50mL/min
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Patients must have adequate cardiac function:
- Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram,
- QTc interval =< 480 ms
Exclusion Criteria:
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Patients must not have known hypersensitivity to binimetinib or compounds of similar chemical or biologic composition
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Patients with melanoma are excluded
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Patients must not have any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases
- NOTE: Patients treated with stereotactic radiotherapy or surgery are eligible if the patient remained without evidence of CNS disease progression >= 3 months. Patients must be off corticosteroid therapy for >= 3 weeks
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Patients must not have a history or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
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Patients must not have a history of retinal degenerative disease
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Patients must not have a history of Gilbert's syndrome
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Patients must not have uncontrolled arterial hypertension despite medical treatment
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Patients must not have active hepatitis B, and/or active hepatitis C infection
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Patients must not have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
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Patients must not have impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
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Patients who have received prior MEK inhibitors are excluded
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: Treatment (binimetinib)
Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Given PO
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Objective Response Rate (ORR)
Zeitfenster: 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
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ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be 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
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
6-Month Progression-free Survival (PFS) Rate
Zeitfenster: 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, from which 6-month PFS 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. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point. |
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, from which 6-month PFS is determined
|
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Progression Free Survival (PFS)
Zeitfenster: 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
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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. Median PFS was estimated using the Kaplan-Meier method. |
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
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Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: James M Cleary, ECOG-ACRIN Cancer Research Group
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Gefäßerkrankungen
- Herz-Kreislauf-Erkrankungen
- Neubildungen nach Standort
- Neubildungen
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Hämatologische Erkrankungen
- Lymphatische Erkrankungen
- Lymphoproliferative Erkrankungen
- Immunproliferative Erkrankungen
- Neubildungen, Plasmazelle
- Hämostasestörungen
- Paraproteinämien
- Bluteiweißstörungen
- Hämorrhagische Störungen
- Hämische und lymphatische Krankheiten
- Hämatologische Neubildungen
- Lymphom
- Multiples Myelom
- Binimetinib
Andere Studien-ID-Nummern
- NCI-2020-03374
- U10CA180820 (US NIH Stipendium/Vertrag)
- U24CA196172 (US NIH Stipendium/Vertrag)
- NCI-2020-03374 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
- EAY131-Z1A (Andere Kennung: CTEP)
- EAY131-Z1A (Andere Kennung: ECOG-ACRIN Cancer Research Group)
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