Testování Copanlisibu jako potenciální cílené léčby u rakoviny s mutacemi PIK3CA (MATCH-Subprotocol Z1F)
Studie fáze II copanlisibu u pacientů s nádory s mutacemi PIK3CA (povolená ztráta PTEN)
This phase II MATCH treatment trial identifies the effects of copanlisib hydrochloride (copanlisib) in patients whose cancer has a genetic change called PIK3CA mutation. Copanlisib may stop the growth of cancer cells by blocking PIK3, a protein needed for cell growth. Researchers hope to learn if copanlisib will shrink this type of cancer or stop its growth.
Přehled studie
Postavení
Podmínky
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 copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment and computed tomography (CT) or magnetic resonance imaging (MRI) at baseline, every 2 cycles for the first 26 cycles, and then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step.
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:
- Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
- Patients must have PIK3CA mutation as determined via the MATCH Master Protocol
- Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
- Patients should stop using herbal medications at least 7 days prior to the first dose of copanlisib. Herbal medications include, but are not limited to: St. John's Wort, Kava, ephedra, gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng
- Patients with type I or II diabetes mellitus must have glycosylated hemoglobin A1c (HbA1c) =< 8.5% within 28 days from registration
- Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L
- Platelets >= 100x10^9/L
- Hemoglobin (Hb) > 9 g/dl
- Total serum bilirubin < 2.0 mg/dL
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) (< 5 x ULN in patients with liver metastases)
- Serum creatinine < 1.5 x ULN
- Men and women of child-bearing potential must agree to use contraception while receiving study treatment and for 1 month after the last dose of copanlisib
Exclusion Criteria:
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Patients must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition
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Patients must not have had prior therapy with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors
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Patients must not have activating KRAS mutations
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Patients must not have HER2 positive (3+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] ratio >= 2) breast cancer
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Patients must not have indolent non-Hodgkin lymphoma (NHL) (follicular lymphoma, small lymphocytic lymphoma [SLL]/chronic lymphocytic leukemia [CLL], lymphoplasmacytic lymphoma [LPL], marginal zone lymphoma) or DLBCL (diffuse large B cell lymphoma)
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Patients must not be on strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and for the duration of study treatment
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Patients must not be on anti-arrhythmic therapy other than digoxin or beta-blockers
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Patients with non-healing wound, ulcer, or bone fracture are not eligible
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Patients with history of or current interstitial pneumonitis are not eligible
- NOTE: For solid tumors, cytomegalovirus (CMV) polymerase chain reaction (PCR) can be obtained at the discretion of treating physician or local institutional guidelines
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 (copanlisib)
Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment and CT or MRI at baseline, every 2 cycles for the first 26 cycles, and then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step. |
Undergo CT
Ostatní jména:
Undergo MRI
Ostatní jména:
Undergo tumor biopsy
Ostatní jména:
Given IV
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Overall 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 30 months 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 analyzable (ie, eligible, treated and PIK3CA mutation status confirmed) patients. Objective response is defined consistent with 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. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is 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 30 months post registration
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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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
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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
|
|
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
|
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 NeuroOncology 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Senthilkumar Damodaran, 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
- 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
- Lymfom
- Mnohočetný myelom
- Vyšetřovací techniky
- Manipulace se vzorkem
- Klinické laboratorní techniky
- Diagnostické techniky a postupy
- Diagnóza
- Chirurgické postupy, operativní
- Cytologické techniky
- Cytodiagnosis
- Diagnostické techniky, chirurgické
- Techniky chemie, analytické
- Analýza spektra
- Biopsie
- Magnetická rezonanční spektroskopie
- Copanlisib
Další identifikační čísla studie
- NCI-2022-06209
- U10CA180820 (Grant/smlouva NIH USA)
- U24CA196172 (Grant/smlouva NIH USA)
- NCI-2022-06209 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- EAY131-Z1F (Jiný identifikátor: CTEP)
- EAY131-Z1F (Jiný identifikátor: ECOG-ACRIN Cancer Research Group)
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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