Clinical trial NCT00374140: Phase II Trial of RAD001 (Everolimus) in Previously Treated Small Cell Lung Cancer
Official title: Phase II Trial of RAD001 (Everolimus) in Previously Treated Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Keywords: small cell
lung
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2006-09-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II, two-stage, open-label, single-agent study of the experimental drug RAD001 (everolimus) in patients with previously treated small cell lung cancer. RAD001 will be administered orally at a dose of 10 mg daily.

Detailed description: This is a phase II, two-stage, open-label, single-agent study of the experimental drug RAD001 (everolimus) in patients with previously treated small cell lung cancer. Patients may have received up to 2 prior chemotherapy regimens for small cell lung carcinoma, but no prior therapy with an m-TOR inhibitor. RAD001 will be administered orally at a dose of 10 mg daily. A cycle will be defined as 3 weeks of study drug administration, and patients will have tumor measurements every 2 cycles. Study participation will continue until disease progression or intolerable toxicities. In addition, in patients who consent, archival tumor tissue (paraffin block from original biopsy) will be collected for research purposes.

Eligibility criteria: Inclusion Criteria:

1. Cytologically or histologically confirmed small cell carcinoma of the lung that has progressed post first-line therapy. Mixed small and non-small cell tumors are excluded.
2. Prior chemotherapy for small cell carcinoma. Up to 2 prior chemotherapy regimens for small cell lung carcinoma are allowed. No prior therapy with an m-TOR inhibitor (e.g. CCI-779).
3. Unidimensionally measurable disease (RECIST criteria). If the only site of measurable disease is in a previously irradiated area, the patient must have documented progression of disease in this area.
4. ECOG performance status 0-2.
5. A minimum of 4 weeks should elapse from prior chemotherapy. Patients must have fully recovered from the effects of any prior surgery or radiation therapy or other anticancer therapies, including immunotherapy and investigational agents.
6. No progressive brain metastases. Brain metastases should have been previously treated with surgery and/or radiation.
7. Patients with a prior malignancy should have at least 3 years of disease-free survival. Prior curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer or other in situ malignancies are allowed.
8. No other coexisting medical condition that would preclude full compliance with the study.
9. Required laboratory values (obtained \< 1 week prior to enrollment):

   * ANC \>/= 1500/mm³
   * Platelets \>/= 100,000/mm³
   * AST and ALT ≤ 3 x ULN (upper limits of normal). In patients with liver metastases AST and ALT should be \< 5 x ULN.
   * Total bilirubin up to 1.5 x ULN (upper limits of normal).
10. Age \>/= 18 years and capacity to give informed consent.
11. Patients should be advised to discontinue drugs that interact with CYP3A4 (see list of examples in Table 3.1 of the full protocol), if medically safe.
12. All patients must have given signed, informed consent prior to registration on study.

Exclusion Criteria:

1. Prior treatment with any investigational agent within the preceding 4 weeks.
2. Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration).
3. A known history of HIV seropositivity.
4. 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).
5. Patients with an active, bleeding diathesis or on anticoagulation (except low dose warfarin).
6. Pregnant and lactating women are excluded from the study because the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk.
7. Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study.
8. Patients should not be on chronic systemic glucocorticoids or other immunosuppressant.

Primary outcomes:
measure: Determine the Proportion of Previously Treated Small Cell Lung Cancer (SCLC) Patients Whose Disease Has Not Progressed Following 6-weeks (2 Cycles) of Treatment With RAD001.
timeFrame: Two cycles of treatment with RAD001 (~6 weeks)
Secondary outcomes:
measure: Overall Survival
timeFrame: From entry in trial to up to 60 months
measure: Progression-free Survival
timeFrame: From entry into trial to up to 60 months
measure: Objective Response Rate
timeFrame: From beginning of treatment up to 60 months
Other outcomes:
Locations:
city: Steubenville
country: United States
facility: UPMC Cancer Center - Teramana Cancer Center - Steubenville
state: Ohio
city: Beaver
country: United States
facility: UPMC Cancer Center - Beaver
state: Pennsylvania
city: Clairton
country: United States
facility: UPMC Cancer Center - Clairton
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Center - Arnold Palmer Pavilion - Greensburg
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Center - Oakbrook Commons - Greensburg
state: Pennsylvania
city: Indiana
country: United States
facility: UPMC Cancer Center - Indiana
state: Pennsylvania
city: Johnstown
country: United States
facility: UPMC Cancer Center - John P. Murtha Pavilion - Johnstown
state: Pennsylvania
city: McKeesport
country: United States
facility: UPMC Cancer Center - McKeesport
state: Pennsylvania
city: Monroeville
country: United States
facility: UPMC Cancer Center - Monroeville
state: Pennsylvania
city: Moon
country: United States
facility: UPMC Cancer Center - Sewickley Medical Oncology/Hematology Group
state: Pennsylvania
city: New Castle
country: United States
facility: UPMC Cancer Center - New Castle
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center - St. Margaret's
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center - Mercy
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute - Hillman Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center - Passavant
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center - Upper St. Clair
state: Pennsylvania
city: Uniontown
country: United States
facility: UPMC Cancer Center - Uniontown
state: Pennsylvania
city: Washington
country: United States
facility: UPMC Cancer Center - Washington
state: Pennsylvania
city: Wexford
country: United States
facility: UPMC Cancer Center - North Hills
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ahmad Tarhini, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: