Phase 1b Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)
Phase 1b Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)
This study is currently recruiting participants.
Verified by Emory University, December 2008
Sponsored by: Emory University
Information provided by: Emory University
ClinicalTrials.gov Identifier: NCT00401778
Purpose
This is a Phase 1b randomized, pre-operative lung cancer trial wherein patients with operable lung cancer will be treated with RAD001 to evaluate clinical response as assessed metabolically by changes in PET scan (50% reduction in standardized uptake value SUV) at baseline and immediately prior to surgery. The safety profile of RAD001 will also be evaluated and the effect of this treatment on survival (both progression-free and overall survival) following surgery and adjuvant chemotherapy (cisplatin and docetaxel).
Condition Intervention Phase
Lung Cancer
Drug: RAD001
Phase I
MedlinePlus related topics: Cancer Lung Cancer Surgery
Drug Information available for: Everolimus
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase 1b Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)
Further study details as provided by Emory University:
Primary Outcome Measures:
Determine clinical response as assessed metabolically by changes in PET scan (50% reduction in SUV) between baseline and immediately prior to surgery. [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
Determine the effects of RAD001 on the regulation of key proteins involved with the mTOR axis in tumor specimens and buccal mucosa in patients with operable non-small cell lung cancer (NSCLC). [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Determine the effects of RAD001 on the inhibition of proliferation (Ki67) and induction of apoptosis (TUNEL assay) in tumor specimens and buccal mucosa from this patient population. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
To determine the safety and tolerability of RAD001 as pre-operative therapy in this patient population. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
To evaluate the effect of RAD001 on progression free survival (PFS) and overall survival (OS) following surgery and chemotherapy and determine if an association exists between clinical outcomes and p70S6K activation. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To determine if pre-operative treatment with RAD001 affects duration of hospital stay following surgery. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Estimated Enrollment: 60
Study Start Date: November 2006
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
RAD001 5 mg/day for 21 days sequentially. Drug: RAD001
Patients will be assigned to one of three treatment arms with RAD001 doses of 5, 7.5 and 10 mg/day for 21 days sequentially taken orally in tablet form.
2: Active Comparator
RAD001 7.5 mg/day for 21 days sequentially. Drug: RAD001
Patients will be assigned to one of three treatment arms with RAD001 doses of 5, 7.5 and 10 mg/day for 21 days sequentially taken orally in tablet form.
3: Active Comparator
RAD001 10 mg/day for 21 days sequentially. Drug: RAD001
Patients will be assigned to one of three treatment arms with RAD001 doses of 5, 7.5 and 10 mg/day for 21 days sequentially taken orally in tablet form.
Detailed Description:
This is a Phase 1b randomized, pre-operative lung cancer trial wherein patients with operable lung cancer will be treated with RAD001 to evaluate clinical response as assessed metabolically by changes in PET scan (50% reduction in standardized uptake value SUV) at baseline and immediately prior to surgery. The safety profile of RAD001 will also be evaluated and the effect of this treatment on survival (both progression-free and overall survival) following surgery and adjuvant chemotherapy (cisplatin and docetaxel).
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 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 60 patients will participate at Emory Winship Cancer Institute and Emory Crawford W. Long Hospital in Atlanta, Georgia.
Eligibility
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Patient must have histologically confirmed Stage I-IIIA non-small cell lung cancer (NSCLC) which is accessible to biopsy.
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 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 ¡Ü 80mm Hg, and angioedema.
Final eligibility for a clinical trial is determined by the health professionals conducting the trial.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00401778
Contacts
Contact: Fadlo Khuri, MD 888-946-7447
Locations
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Fadlo Khuri, MD
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Fadlo Khuri, MD Emory University Winship Cancer Institute
More Information
Responsible Party: Winship Cancer Institute ( Fadlo Khuri, MD )
Study ID Numbers: 1341-2004
Study First Received: November 17, 2006
Last Updated: December 8, 2008
ClinicalTrials.gov Identifier: NCT00401778 [history]
Health Authority: United States: Institutional Review Board; United States: Food and Drug Administration
Keywords provided by Emory University:
Lung Cancer
Study placed in the following topic categories:
Everolimus
Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma
Additional relevant MeSH terms:
Neoplasms by Site
Immunologic Factors
Respiratory Tract Neoplasms
Physiological Effects of Drugs
Neoplasms
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms by Histologic Type
ClinicalTrials.gov processed this record on February 10, 2009
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