Phase I/II Trial of RAD001 Plus Docetaxel in Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer

This is an open-label, single-arm, Phase I/II trial to determine the safety of RAD001 in combination with docetaxel and compare the efficacy of RAD001 plus docetaxel versus published Phase II and III reports of docetaxel alone in patients with recurrent NSCLC.

This is an open-label, single-arm, Phase I/II trial to determine the safety of RAD001 in combination with docetaxel and compare the efficacy of RAD001 plus docetaxel versus published Phase II and III reports of docetaxel alone in patients with recurrent NSCLC.

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 58 patients will participate at Emory Winship Cancer Institute and Emory Crawford W. Long Hospital in Atlanta, Georgia.

Eligibility Criteria:
Inclusion Criteria:

* Patients must have histologically confirmed non-small cell lung cancer (NSCLC) which is accessible to biopsy.
* Patient must have ECOG Performance Status of 0, 1, or 2.
* Life expectancy greater than 12 weeks.
* Patient must have adequate bone marrow, renal and hepatic function as defined in the protocol.
* Completed all prior therapy at least 3 weeks prior to registration and be adequately recovered from that therapy.
* Must be at least 18 years of age.
* Meet pre-entry requirements as specified in Section 7.0.
* Female patients of child-bearing potential must have a negative serum pregnancy test prior to study entry.
* 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.
* Patient must not have more than one prior chemotherapy regimen.
* Final eligibility for a clinical trial is determined by the health professionals conducting the trial.

Exclusion Criteria:

* Chronic treatment with systemic steroids or other immunosuppressive agents.
* Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
* A known history of HIV seropositivity.
* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
* Patients with an active, bleeding diathesis or an oral anti-vitamin K medication (except low dose coumadin).
* Known hypersensitivity to everolimus, sirolimus, or any of its excipients.
* Patient is pregnant or breast-feeding.
* Patient has intercurrent illness including, but not limited to: ongoing active or severe infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, myocardial infarction within 6 months, uncontrolled diabetes mellitus, chronic liver or renal disease, active upper GI tract ulceration or psychiatric illness/social situations that would limit compliance with study requirements.
* Patient is unable to swallow RAD001.
* History of other invasive malignancies, with the exception of non-melanoma skin cancer, if there is any evidence of the malignancy being present within the past 5 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.
* Patient has received treatment with an investigational agent within 4 weeks of registration.
* Final eligibility for a clinical trial is determined by the health professionals conducting the trial.