Phase 1b Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC) - Full Text View

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 the target effects of this compounds on relevant molecular pathways and on the FDG uptake of the tumor by a PET scan at baseline and immediately prior to surgery. The safety profile of RAD001 will also be evaluated.

Condition	Intervention	Phase
Lung Cancer	Drug: RAD001	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 1b Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:

Determine clinical response as assessed metabolically by changes in PET scan 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 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:	35
Study Start Date:	November 2006
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 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, and 10 mg/day for 21-28 days sequentially taken orally in tablet form. Other Name: Everolimus
Active Comparator: 3 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, and 10 mg/day for 21-28 days sequentially taken orally in tablet form. Other Name: Everolimus

Detailed Description:

This is a Phase 1b randomized, 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 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.

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 ≤ 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: Suresh Ramalingam, MD

888-946-7447

Locations

United States, Georgia
Emory University Winship Cancer Institute	Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Suresh Ramalingam, MD

Sponsors and Collaborators

Emory University

Investigators

Principal Investigator:

Suresh Ramalingam, MD

Emory University Winship Cancer Institute

More Information

No publications provided

Responsible Party:	Suresh S. Ramalingam, Principal Investigator, Emory University
ClinicalTrials.gov Identifier:	NCT00401778 History of Changes
Other Study ID Numbers:	1341-2004
Study First Received:	November 17, 2006
Last Updated:	November 13, 2012
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by Emory University:

Lung Cancer

Additional relevant MeSH terms:

Lung Neoplasms
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Everolimus
Sirolimus
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Lung Diseases

Respiratory Tract Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 21, 2013