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

NCT00401778 | Completed Phase 1 Results DMC

• 1 other identifier: IRB00024810
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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 positron emission tomography (PET) scan at baseline and immediately prior to surgery. The safety profile of RAD001 will also be evaluated.

Conditions

Lung Cancer

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Clinical Response as Assessed Metabolically by Changes in Positron Emission Tomography (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

• 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

• Inhibition of Proliferation (Ki67) and Induction of Apoptosis (TUNEL Assay) in Tumor Specimens and Buccal Mucosa.

  6 months

Secondary Outcomes (2)

• Safety and Tolerability of RAD001 as Pre-operative Therapy.

  6 months

• Duration of Hospital Stay Following Surgery.

  6 months

Study Arms (3)

1

ACTIVE COMPARATOR

RAD001 5 mg/day for 21 days sequentially.

Drug: RAD001

3

ACTIVE COMPARATOR

RAD001 10 mg/day for 21 days sequentially.

Drug: RAD001

Control

NO INTERVENTION

Patients who are eligible for the study but choose not to receive RAD001 treatment.

Interventions

RAD001 DRUG

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.

Also known as: Everolimus

1; 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Suresh S. Ramalingam, MD
• Organization: Emory University

ssramal@emory.edu

404-778-5378

Study Officials

• Suresh Ramalingam, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 17, 2006
• First Posted: November 22, 2006
• Study Start: November 1, 2006
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 21, 2016
• Results First Posted: July 14, 2015

Record last verified: 2016-11

Locations

US (1)