Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

Lung Cancer Clinical Trial

Official title:

Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00401778
• Other study ID #: IRB00024810
• Status: Completed
• Phase: Phase 1
• First received: November 17, 2006
• Last updated: June 18, 2015
• Start date: November 2006
• Est. completion date: December 2013

Study information

• Verified date: June 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1b 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 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Response as Assessed Metabolically by Changes in PET Scan Between Baseline and Immediately Prior to Surgery.	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.	Day 21	No
Primary	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).	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.	6 months	No
Primary	Inhibition of Proliferation (Ki67) and Induction of Apoptosis (TUNEL Assay) in Tumor Specimens and Buccal Mucosa.		6 months	Yes
Secondary	Safety and Tolerability of RAD001 as Pre-operative Therapy.		6 months	Yes
Secondary	Duration of Hospital Stay Following Surgery.		6 months	Yes