- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00401778
Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)
Studieoversikt
Detaljert beskrivelse
This is a Phase 1b pre-operative lung cancer trial wherein patients with operable lung cancer will be treated with RAD001 for 3-4 weeks to study the effects of the novel agent in relevant molecular pathways. The study will also assess the FDG uptake of the tumor at baseline and upon completion of therapy (before surgery) with a PET scan. The safety profile of RAD001 will also be evaluated.
New agents and regimens are urgently needed for lung cancer treatment. With the development of novel agents and small molecules designed to curtail the aggressive aspects of this disease, some progress has been realized. However, much more effort and insight will be required for further real gains to be made. We propose that studying the mammalian target of rapamycin (mTOR) axis, known to be abnormal in non-small cell lung cancer (NSCLC), and translating that knowledge into therapeutic adjustments can lead to meaningful advances in lung cancer treatment.
Approximately 35 patients will participate at Winship Cancer Institute of Emory University in Atlanta, Georgia.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
Georgia
-
Atlanta, Georgia, Forente stater, 30322
- Emory University Winship Cancer Institute
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Patient must have histologically confirmed Stage I-IIIA non-small cell lung cancer (NSCLC) which is accessible to biopsy.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- Life-expectancy greater than 6 months.
- Adequate bone marrow, renal, hepatic, pulmonary and cardiac function as defined in the protocol.
- Patient must be at least 18 years of age.
- Must meet pre-entry requirements for timing of study parameters as specified in section 7.0.
- Female patients of child-bearing potential must have a negative serum pregnancy test within 48 hours of study initiation and be non-lactating.
- Patients of child-bearing potential must agree to use an effective form of contraception while on study and for 3 months following completion of study treatment.
- The use of granulocyte-colony stimulating factor (G-CSF) will be permitted in study participants.
- Final eligibility for a clinical trial is determined by the health professionals conducting the trial.
Exclusion Criteria:
- Patient has received previous treatment for NSCLC.
- Known hypersensitivity to everolimus, sirolimus, or any of its excipients.
- Patient is pregnant or breast-feeding.
- Patient has incurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patient is unable to swallow RAD001 tablet.
- History of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of the malignancy being present within the past five years.
- History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80. Symptoms may include any reaction such as bronchospasm, generalized urticaria, systolic BP ≤ 80mm Hg, and angioedema.
- Final eligibility for a clinical trial is determined by the health professionals conducting the trial.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Aktiv komparator: 1
RAD001 5 mg/day for 21 days sequentially.
|
Patients will be assigned to one of three treatment arms with RAD001 doses of 5, and 10 mg/day for 21-28 days sequentially taken orally in tablet form.
Andre navn:
|
Aktiv komparator: 3
RAD001 10 mg/day for 21 days sequentially.
|
Patients will be assigned to one of three treatment arms with RAD001 doses of 5, and 10 mg/day for 21-28 days sequentially taken orally in tablet form.
Andre navn:
|
Ingen inngripen: Control
Patients who are eligible for the study but choose not to receive RAD001 treatment.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Clinical Response as Assessed Metabolically by Changes in Positron Emission Tomography (PET) Scan Between Baseline and Immediately Prior to Surgery.
Tidsramme: Day 21
|
All patients had baseline imaging in a fasted state with 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18FDG)-PET scan and a repeat scan at 3 to 4 weeks later using routine clinical protocol for patient preparation, radiotracer administration and data acquisition.
The repeat imaging occurred no longer than 24 hours before surgical resection.
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Day 21
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Effects of RAD001 on the Regulation of Key Proteins Involved With the Mammalian Target of Rapamycin (mTOR) Axis in Tumor Specimens and Buccal Mucosa in Patients With Operable Non-small Cell Lung Cancer (NSCLC).
Tidsramme: 6 months
|
Changes in the expression of key signaling proteins in the mTOR/phosphatidylinositol 3-kinase (PI3K) pathway were determined by immunohistochemistry using previously published protocols and manufacturers' recommendations for antigen retrieval and antibody dilution along with positive and negative controls.
Two investigators assessed protein expression jointly by light microscopy.
The degree of expression was assessed by intensity (0, 1+, 2+, 3+) and percentage of cell staining in line with published algorithm.
A derivative score (immunoscore) ranging between 0 and 300 was calculated as the product of intensity and percent cell staining.
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6 months
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Inhibition of Proliferation (Ki67) and Induction of Apoptosis (TUNEL Assay) in Tumor Specimens and Buccal Mucosa.
Tidsramme: 6 months
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6 months
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
Safety and Tolerability of RAD001 as Pre-operative Therapy.
Tidsramme: 6 months
|
6 months
|
Duration of Hospital Stay Following Surgery.
Tidsramme: 6 months
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6 months
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Suresh Ramalingam, MD, Emory University Winship Cancer Institute
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- IRB00024810
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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