- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01939418
Phase Ib/II Trials of RAD001 in Triple Negative Metastatic Breast Cancer
A Phase Ib Trial of Gemcitabine and Cisplatin With RAD001 in Patients With Metastatic Triple Negative Breast Cancer Proceeding to an Open Label Randomized Phase II Trial Comparing Gemcitabine/Cisplatin With or Without RAD001.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
PIK3CA active mutations are the most frequent genetic event in breast cancer, including in TNBC which presents activated PI3K/AKT signaling due to PIK3CA mutation or PTEN deficiency. TNBC cell lines having activated PI3K/AKT signaling showed a high sensitivity to PI3K/mTOR inhibitors. RAD001 is a potent mTOR complex 1 inhibitor and showed to enhance cisplatin or gemcitabine induced apoptosis by inhibiting p53 induced p21 expression.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
Gyeonggido
-
Goyangsi, Gyeonggido, Korea, Republikken, 410-769
- National Cancer Center
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Females with histologically confirmed, metastatic or stage IV breast cancer
- ER/PgR negative or poor (Allred score ≤ 3/8) and HER2 negative breast cancer
- ECOG performance status 0-2
- Age ≥ 20 years
- Previously treated by anthracycline and taxane in adjuvant/neoadjuvant or metastatic setting
- ≤ 2 chemotherapy regimens for metastatic disease
- Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.
- CNS metastasis is permitted if asymptomatic and not requiring treatment with steroids and is documented to be non-progressing at study entry
- Presence of measurable or evaluable disease by RECIST 1.1 criteria
- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet ≥100,000/mm3, hemoglobin ≥ 10g/mm3
- Adequate hepatic function: total bilirubin ≤ 1.5 x upper normal limit (UNL), AST/ALT ≤2.5 x UNL or ≤5 x UNL if presented with hepatic metastasis
- Fasting serum cholesterol ≤ 300mg/dl and fasting triglycerides ≤ 2.5 x UNL
- Adequate renal function: Serum creatinine ≤1.5mg/dL
- Patients should sign a written informed consent before study entry
- Patients with positive HBV-DNA of HBsAg at screening must initiate prophylaxis with appropriate antiviral medication at least one week prior to treatment start
Exclusion Criteria:
- Known active CNS metastasis
- Patients who received prior therapy with gemcitabine
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
- Patients with more than 3 prior chemotherapy lines for treating metastatic breast cancer.
- Patients who received prior therapy with mTOR inhibitor or PI3K inhibitor
- Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
- Radiotherapy within four weeks prior to enrolment, except radiotherapy to the bone for analgesic purpose or for lytic lesions at risk of fracture. Patients must have recovered from radiotherapy toxicities prior to enrolment.
- Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Active ulceration of upper gastrointestinal tract
- Other concurrent severe and/or uncontrolled conditions (e.g. uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol.
- Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
- Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A at enrolment (rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) continuously for at least 7 days during any time period in the last 2 weeks prior to enrolment
- Known hypersensitivity to protocol treatment
- Pregnant or breast feeding
- Peripheral neuropathy ≥ grade 2 (NCI CTCAE version 4.0) at randomization
- Patients unwilling to or unable to comply with the protocol
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: RAD001
gemcitabine 800mg/m2, D1 and D8 iv.
every 3 weeks.
cisplatin 30mg/m2, D1 and D8 iv.
every 3 weeks.
RAD001 5mg QD. po.
|
Afinitor 5mg qd. po.
Andre navne:
gemcitabine 800mg/m2 iv.
D1 and D8 every 3 weeks
cisplatin 30mg/m2 iv.
D1 and D8 every 3 weeks
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer
Tidsramme: up to 1 year
|
phase IB part
|
up to 1 year
|
Efficacy of gemcitabine and cisplatin with or without RAD001 in patients with metastatic triple-negative breast cancer by evaluating progression free survival (PFS)
Tidsramme: up to 5 years
|
phase II part
|
up to 5 years
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine/cisplatin/RAD001
Tidsramme: up to 1 year
|
phase Ib part
|
up to 1 year
|
number of patients with adverse events as a measure of safety and tolerability
Tidsramme: up to 5 years
|
phase Ib and phase II
|
up to 5 years
|
objective response rate
Tidsramme: up to 1 year
|
phase Ib and phase II
|
up to 1 year
|
Overall survival (OS)
Tidsramme: up to 5 years
|
phase Ib and phase II
|
up to 5 years
|
check biomarkers associated with the response of RAD001: angiogenesis, metabolism, immune cells profiles
Tidsramme: up to 5 years
|
phaseIb and phaseII
|
up to 5 years
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: In Hae Park, Doctor, National Cancer Center, Korea
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hudsygdomme
- Neoplasmer
- Neoplasmer efter sted
- Brystsygdomme
- Brystneoplasmer
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Antivirale midler
- Enzymhæmmere
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Gemcitabin
- Everolimus
Andre undersøgelses-id-numre
- NCCCTS-13-670
- 12491 (Anden identifikator: Korea Food and Drug Administration)
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med Metastatisk brystkræft
-
Cairo UniversityIkke rekrutterer endnu
-
Abouqir General HospitalAlexandria UniversityRekrutteringBreast Udseende Rekonstruktion DisproportionEgypten
-
Tianjin Medical University Cancer Institute and...Guangxi Medical University; Sun Yat-sen University; Chinese PLA General Hospital og andre samarbejdspartnereAfsluttetDen kliniske anvendelsesvejledning af Conebeam Breast CTKina
-
ETOP IBCSG Partners FoundationAfsluttetBreast Cancer Invasive NosItalien
-
Spanish Breast Cancer Research GroupHoffmann-La Roche; Roche Farma, S.AAfsluttetBreast Cancer Invasive NosSpanien
-
Ontario Clinical Oncology Group (OCOG)Afsluttet
-
Pomeranian Medical University SzczecinMaria Sklodowska-Curie National Research Institute of Oncology; Regional...UkendtBRCA1 mutation | Breast Cancer Invasive NosPolen
-
Aga Khan UniversityAfsluttetBrystkræft | Perforatorklap | Brysttumor | Oncoplasty | Breast-QPakistan
-
University Health Network, TorontoAfsluttetBreast Cancer Invasive Nos | Primær invasiv brystkræftCanada
-
KU LeuvenNovartisUkendtER Positive, HER2 Negative Breast Cancer NeoplasmaBelgien
Kliniske forsøg med RAD001
-
Children's Hospital Medical Center, CincinnatiNovartisAfsluttetTuberøs sklerose | AngiolipomForenede Stater
-
Novartis PharmaceuticalsAfsluttetMetastatisk nyrecellekarcinom (mRCC)Tyskland
-
University of Alabama at BirminghamNational Cancer Institute (NCI); Children's Hospital of Philadelphia; Washington... og andre samarbejdspartnereAfsluttet
-
Novartis PharmaceuticalsAfsluttet
-
Novartis PharmaceuticalsAfsluttetLymfangioleiomyomatose (LAM) | Tuberøs sklerosekompleks (TSC)Forenede Stater, Det Forenede Kongerige, Tyskland, Italien, Den Russiske Føderation, Holland, Japan, Canada, Polen, Frankrig, Spanien
-
Radiation Therapy Oncology GroupNational Cancer Institute (NCI); NRG OncologyAfsluttetTumorer i hjernen og centralnervesystemetForenede Stater, Israel, Canada
-
Guangdong Provincial People's HospitalNovartisUkendtNeuroendokrine tumorer | Carcinoid tumorKina
-
Fox Chase Cancer CenterRekrutteringMetastatisk bugspytkirtelkræftForenede Stater
-
Novartis PharmaceuticalsAfsluttetHepatocellulært karcinomForenede Stater, Spanien, Korea, Republikken, Holland, Taiwan
-
Novartis PharmaceuticalsAfsluttetNeuroendokrint karcinom i lunge og thymusItalien, Det Forenede Kongerige, Holland, Spanien, Tyskland, Frankrig, Grækenland, Danmark, Sverige