Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
20. november 2017 opdateret af: Celgene
A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
This is a Phase 1 clinical trial examining the safety, pharmacokinetics and pharmacodynamics of escalating doses of the proteasome inhibitor NPI-0052 in patients with advanced malignancies including solid tumors, lymphomas, leukemias and multiple myeloma.
By inhibiting proteasomes NPI-0052 prevents the breakdown of proteins involved in signal transduction, which blocks growth and survival in cancer cells.
Studieoversigt
Status
Afsluttet
Betingelser
Detaljeret beskrivelse
Patients were enrolled in 1 of 2 study arms. Arm AM (weekly doses of NPI-0052) consisted of patients with solid and hematological malignancies excluding multiple myeloma (MM), and these patients received NPI-0051 once weekly for 3 weeks of every 4 weeks. Arm MM (twice-weekly doses of NPI-0052) consisted of patients with MM and other hematological malignancies, and these patients received NPI-0052 twice weekly for 2 weeks of every 3 weeks. All patients received NPI-0052 administered IV over approximately 1 to 120 minutes. Patients with MM (Arm MM) also received 20 mg dexamethasone per orally or IV on the day before and the day of NPI-0052 dosing.
Patients were initially enrolled in dose-escalating cohorts to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of NPI-0052. Once the RP2D was determined for each arm of the study, the RP2D was evaluated in the dose-expansion stage of the study.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
86
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Queensland
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South Brisbane, Queensland, Australien, 4101
- Mater Adult Hospital
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South Australia
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Woodville South, South Australia, Australien, 5001
- The Queen Elizabeth Hospital
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Victoria
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Melbourne, Victoria, Australien, 3002
- Peter MacCallum Cancen Center
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Melbourne, Victoria, Australien, 3168
- The Alfred Hospital
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Wodonga, Victoria, Australien, 3690
- Border Medical Oncology
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Western Australia
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Nedlands, Western Australia, Australien, 6009
- Sir Charles Gairdner Hospital and University of Western Australia
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Perth, Western Australia, Australien, 6001
- Royal Perth Hospital
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Karnofsky Performance Status (KPS) > 70%.
- Histologically-confirmed advanced malignancy for which a standard, approved therapy is not available.
- Adequate renal, liver, pancreatic and hematologic function
- Signed informed consent (sample IC form is provided in Appendix A).
Exclusion Criteria
- Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 28 days
- Patients that require G-CSF and/or platelet support during screening and are likely to require G-CSF and/or platelet support for the duration of the clinical trial.
- Patients with ongoing coagulopathies and/or taking anticoagulants
- Patients receiving intrathecal therapy.
- Known brain metastases.
- Pre-existing adrenal insufficiency; concomitant therapy with replacement corticosteroids. Pre-existing acute or chronic pancreatitis.
- Significant cardiac disease.
- Pregnant or breast-feeding women.
- Concurrent, active secondary malignancy for which the patient is receiving therapy. (Lymphoma patients with a diagnosis of a potentially hormone-sensitive tumor who are without evidence of disease for this second malignancy may continue to receive hormonal therapy).
- Patients with proteinuria Grade 2 or greater
- Active uncontrolled bacterial or fungal infection requiring systemic therapy; infection requiring parenteral antibiotics.
- Patients who are known to be HIV positive or have active Hepatitis A, B, or C infection.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Arm AM: advanced malignancies
Dose Escalation - 9 dose cohorts NPI-0052 on Days 1, 8, 15 every 28 days NPI-0052 doses ranging from 0.1 to 0.9 mg/m2
|
NPI-0052 dose ranging from 0.1 to 0.9 mg/m2 NPI-0052 IV injection over 1 to 120 minutes on Days 1, 8, and 15 of 4-week cycles
Andre navne:
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|
Eksperimentel: Arm MM: multiple myeloma
Dose Escalation - 8 dose cohorts NPI-0052 on Days 1, 4, 8, 11 every 21 days NPI-0052 doses ranging from 0.075 to 0.6 mg/m2 Dexamethasone 20 mg oral or IV day before and day after NPI-0052 dosing.
|
NPI-0052 dose ranging from 0.075 to 0.6 mg/m2 NPI-0052 IV injection over 1 to 120 minutes on Days 1, 4, 8, and 11 of 3-week cycles
Andre navne:
20 mg oral or IV day before and day after NPI-0052 dosing.
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052
Tidsramme: Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
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Assess dose-limiting toxicities during Cycle 1 for each treatment arm
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Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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To evaluate the pharmacokinetics activity of NPI-0052
Tidsramme: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1
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the assess the time course of NPI-0052 in the body
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Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1
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To evaluate the safety and tolerability of NPI-0052
Tidsramme: Treatment period through 28-days after the last dose of study drug
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Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
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Treatment period through 28-days after the last dose of study drug
|
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To evaluate the pharmacodynamics of NPI-0052
Tidsramme: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycles 1 and 2 and of every other cycle thereafter through study completion
|
proteasome inhibition in blood samples
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Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycles 1 and 2 and of every other cycle thereafter through study completion
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Studieleder: Steven D Reich, MD, Triphase Research and Development I Corp
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2007
Primær færdiggørelse (Faktiske)
1. april 2013
Studieafslutning (Faktiske)
1. april 2013
Datoer for studieregistrering
Først indsendt
26. februar 2008
Først indsendt, der opfyldte QC-kriterier
5. marts 2008
Først opslået (Skøn)
6. marts 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
22. november 2017
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
20. november 2017
Sidst verificeret
1. november 2017
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Neoplasmer
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Autonome agenter
- Agenter fra det perifere nervesystem
- Enzymhæmmere
- Anti-inflammatoriske midler
- Antineoplastiske midler
- Antiemetika
- Gastrointestinale midler
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Antineoplastiske midler, hormonelle
- Proteasehæmmere
- Dexamethason
- Proteasomhæmmere
Andre undersøgelses-id-numre
- NPI-0052-102
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
UBESLUTET
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