- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT02448329
Study of AZD1775 in Combination With Paclitaxel, in Advanced Gastric Adenocarcinoma Patients Harboring TP53 Mutation as a Second-line Chemotherapy
This study is a single arm, single center phase II study of AZD1775 in combination with paclitaxel in patients with advanced gastric adenocarcinoma harboring TP53 mutation as a second-line chemotherapy.
Patients will receive AZD 1775 plus weekly paclitaxel combination regimen. The arm is composed of 25 patients.
AZD1775 225 mg BID q 12 hours (x 5 doses) administered days 1~3 + paclitaxel 80 mg/m2 given days 1, 8 and 15 of a 28 day cycle.
Tumour evaluation using Response Evaluation Criteria in Solid Tumors 1.1 will be conducted at screening every 16 weeks until objective disease progression .
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
AZD1775 is an inhibitor of Wee1, a protein tyrosine kinase. Wee1 phosphorylates and inhibits cyclin-dependent kinases 1 (CDK1) and 2 (CDK2), and is involved in regulation of the intra-S and G2 cell cycle checkpoints.
In in vitro and in vivo preclinical models, AZD1775 selectively enhanced chemotherapy induced death of cells deficient in p53 signaling. Tumor context-specific sensitization to the DNA damaging agents gemcitabine and platinums was observed in TOV21G (ovarian carcinoma) cell lines matched for wild type and knock down of p53.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
-
-
-
Seoul, Korejská republika, 135-710
- Samsung Medical Center
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Provision of fully informed consent prior to any study specific procedures.
- Patients must be ≥20 years of age.
Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after first line therapy.
- The 1st line regimen must have contained doublet 5-fluoropyrimidine or platinum based regimen.
- Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doublet 5-fluoropyrimidine and platinum-based regimen could be considered as 1st line therapy.
- Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
- Provision of tumor sample (from either a resection or biopsy)
- Patients with p53mutation
- Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- Eastern Cooperative Oncology Group performance status 0-1
- Patients must have a life expectancy ≥ 3 months from proposed first dose date.
Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
- Haemoglobin ≥9.0 g/dL (transfusion allowed)
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- White blood cells (WBC) > 3 x 109/L
- Platelet count ≥100 x 109/L (transfusion allowed)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- aspartate aminotransferase (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
- Serum creatinine ≤1.5 x institutional ULN
- At least one measurable lesion that can be accurately assessed by imaging or physical examination at baseline and following up visits.
- Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1.
Exclusion Criteria:
- More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
- Any previous treatment with P53 inhibitors (small molecules)
- Any previous treatment with paclitaxel
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer,curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≤5 years.
- HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
- Patients unable to swallow orally administered medication.
- Treatment with any investigational product during the last 14 days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
- Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
- Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole,ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
- With the exception of alopecia, any ongoing toxicities (>Common Toxicity Criteria for Adverse Effects grade 1) caused by previous cancer therapy.
- Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
- Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24hour period or family history of long QT syndrome.
- Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) Left ventricular ejection fraction <55% measured by echocardiography, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment
- Ophthalmological conditions as follows:Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure), Current or past history of central serous retinopathy or retinal vein occlusion
- Female patients who are breast-feeding or child-bearing
- Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
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 |
---|---|
Experimentální: AZD1775 in Combination With Paclitaxel
AZD1775 225 mg BID q 12 hours (x 5 doses, 2.5 days) administered days 1~3 Weekly paclitaxel 80 mg/m2 IV on 1, 8 and 15 of a four week l cycle is an widely used dose of paclitaxel given on this schedule in gastric adenocarcinoma patients as second-line therapy.
|
AZD1775 225 mg BID q 12 hours (x5 doses, 2.5 days) administered days 1~3
paclitaxel 80 mg/m2 given days 1, 8 and 15 of a 28 day cycle
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
---|---|
Objective response rate (ORR)
Časové okno: 8weeks
|
8weeks
|
Sekundární výstupní opatření
Měření výsledku |
Časové okno |
---|---|
Duration of response
Časové okno: 24weeks
|
24weeks
|
Disease control rate
Časové okno: 8weeks
|
8weeks
|
Overall survival
Časové okno: 24weeks
|
24weeks
|
progression-free survival (PFS)
Časové okno: 24weeks
|
24weeks
|
safety and tolerability measured by Adverse Events,Vital signs,Collection of clinical chemistry/haematology parameters,ECGs
Časové okno: 24weeks
|
24weeks
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
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
- Novotvary podle histologického typu
- Novotvary
- Karcinom
- Novotvary, žlázové a epiteliální
- Adenokarcinom
- Molekulární mechanismy farmakologického působení
- Inhibitory enzymů
- Antineoplastická činidla
- Tubulinové modulátory
- Antimitotické látky
- Modulátory mitózy
- Antineoplastické látky, fytogenní
- Paklitaxel
- Adavosertib
Další identifikační čísla studie
- 2014-04-127
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
Klinické studie na AZD1775
-
NYU Langone HealthUkončenoAkutní myeloidní leukémie | Myelodysplastické syndromy | MyelofibrózySpojené státy
-
AstraZenecaDokončenoRakovina vaječníků | Lokálně pokročilé solidní nádory | Metastatické pevné nádorySpojené státy
-
AstraZenecaParexelUkončenoPokročilé pevné nádorySpojené království, Spojené státy
-
AstraZenecaUkončenoDříve léčená nemalobuněčná rakovina plicSpojené státy
-
AstraZenecaParexelDokončenoSerózní karcinom dělohySpojené státy, Itálie, Španělsko, Francie, Kanada
-
Samsung Medical CenterUkončenoMalobuněčný karcinom plicKorejská republika
-
Dana-Farber Cancer InstituteAstraZenecaAktivní, ne náborRakovina dělohySpojené státy
-
AstraZenecaQuintiles, Inc.DokončenoSolidní nádoryFrancie, Spojené království, Holandsko
-
National Cancer Institute (NCI)Dokončeno
-
St. Joseph's Hospital and Medical Center, PhoenixBarbara Ann Karmanos Cancer Institute; American Society of Clinical Oncology; Translational Genomics Research Institute a další spolupracovníciDokončeno