- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00466102
Efficacy of RAD001 in Breast Cancer Patients With Bone Metastases (RADAR)
RADAR: A Randomized Discontinuation Phase II Study to Determine the Efficacy of RAD001 in Breast Cancer Patients With Bone Metastases
Studieoversigt
Detaljeret beskrivelse
RAD001 is an orally bioavailable and well tolerated rapamycin ester analogue, which acts by selectively inhibiting mTOR (mammalian target of rapamycin). mTor is an intracellular protein kinase implicated in the control of cellular proliferation in neoplastic cells. Treatment with RAD001 has been shown to inhibit these signalling events and leads to growth retardation of tumour cells. In addition RAD001 in vitro stops the formation and activity of osteoclasts. Therefore a therapy of advanced breast cancer with progressive bone metastases seems to be reasonable with RAD001.
Comparison:
All patients receive RAD001 in an 8 week run in phase. Patients who show a response after 8 weeks will continue receiving RAD001. All patients with stable disease after the run in phase will be randomised to receive either RAD001 or placebo and will be followed up until progression of disease. Patients with progressive disease after the 8 week run in phase will be withdrawn from the trial.
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
-
-
Schleswig-Holstein
-
Kiel, Schleswig-Holstein, Tyskland, 24105
- Dr. med. Christoph Mundhenke
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- Histologically confirmed invasive adenocarcinoma of the breast.
- Primary tumour or metastasis negative or positive (≥ 10% positive stained cells) for oestrogen and/or progesterone receptor detected by immunohistochemistry.
- Single or multiple bone metastasis (x-ray, CT or MRI) as only metastatic site.
- Postmenopausal hormone receptor positive patients should have received an aromatase inhibitor in any given previous breast cancer therapy. Concurrent endocrine treatment for metastatic bone disease is obligatory. Previous treatment with bisphosphonates is allowed.
- Up to one previous chemotherapy for metastatic disease is allowed.
- Patients must have either measurable or non-measurable target lesions according to the WHO criteria.
- At least 1 target lesion must be completely outside the radiation portal or there must be pathologic proof of progressive disease.
- At least 2 weeks since major surgery with full recovery.
- Complete staging within 4 weeks prior to registration.
- Karnofsky performance status evaluation > 60%.
- Age >18 years.
- Absolute neutrophil count >1,500 cells/µl, platelet count >100,000 cells/µl.
- Bilirubin >1.5x the upper normal limit for the institution (UNL); elevation of transaminases, alkaline phosphatase < 2.5x UNL and serum albumin < 30g/l. Normal renal function (creatinine >1.5x upper normal limit)
- If of childbearing potential, negative pregnancy test. In addition the patient has to agree to use an effective method to avoid pregnancy for the duration of the study.
Exclusion Criteria:
- Known hypersensitivity reaction to the compounds or incorporated substances (e.g. everolimus or sirolimus [rapamycin] or lactose).
- Concurrent immunotherapy or hormone replacement therapy and use of hormonal contraceptives.
- Need for chemotherapy or irradiation of bone metastasis during study treatment
- HER2 positive primary tumour and/or lesion
- Evidence of metastasis in other organs
- Uncompensated diabetes mellitus; fasting value of blood sugar of >120 (mg/dl)
- Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/l) or > 12.0 mg/dl (3.00 mmol/l)
- Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute
- Life expectancy of less than 3 months
- Serious intercurrent medical or psychiatric illness that may interfere with the planned treatment (including AIDS and serious active infection).
- History of other malignancy within the last 5 years which could affect the diagnosis or assessment of metastatic breast cancer
- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (e.g. rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, ritonavir, telithromycin, erythromycin, verapamil, dilitazem) within the last 5 days or the expected need for these treatments during study participation.
- Pregnant or nursing women.
- The patient is not accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre which could be the Principal or Co-Investigator's site.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Tredobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Aktiv komparator: 1
Patients with stable disease after 8 week run in randomized to RAD001 (blinded)
|
Tablet of 5 mg, 2 tablets (10 mg) are taken once daily during study therapy
|
Placebo komparator: 2
Patients with stable disease after 8 week run in receive placebo (blinded)
|
2 tablets are taken once daily during study therapy
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
To determine the time to progression (TTP) in patients with no change in bone metastases after an 8 week run in treatment with RAD001 compared to placebo
Tidsramme: 40 weeks
|
40 weeks
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
To determine the objective response rate after 8 weeks of RAD001
Tidsramme: 8 weeks
|
8 weeks
|
To determine the TTP in patients with a response after 8 weeks of RAD001
Tidsramme: 8 weeks
|
8 weeks
|
To determine the overall clinical benefit defined as CR, PR or stable disease > 24 weeks for patients continuing RAD001 after the 8 week run in phase
Tidsramme: 40 weeks
|
40 weeks
|
To evaluate the safety and toxicity of RAD001
Tidsramme: 40 weeks
|
40 weeks
|
To assess the frequency of bone related events
Tidsramme: 40 weeks
|
40 weeks
|
To assess changes of pain intensity during treatment
Tidsramme: 40 weeks
|
40 weeks
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Nicolai Maass, MD, Prof., Universitätsfrauenklinik Aachen
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- GBG 41
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 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