Clinical trial NCT00096486: Gefitinib and Everolimus in Treating Patients With Stage IIIB or Stage IV or Recurrent Non-Small Cell Lung Cancer
Official title: A Phase I/II Trial of Fixed Doses of Daily Gefitinib With Escalating Doses of Daily RAD001 in Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-11-10
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Gefitinib and everolimus may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving gefitinib together with everolimus may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects, best way to give, and best dose of giving gefitinib with everolimus and to see how well it works in treating patients with stage IIIB or stage IV or recurrent non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the maximum tolerated dose of everolimus when administered with gefitinib in patients with stage IIIB or IV or recurrent non-small cell lung cancer. (Phase I)
* Determine the efficacy of this regimen in these patients. (Phase II)

Secondary

* Assess the pharmacokinetics of everolimus, alone and in combination with gefitinib, in these patients. (Phase I)

OUTLINE: This is an open-label, phase I, dose-escalation study of everolimus followed by a phase II study.

* Phase I: Patients receive oral everolimus once on day 1. Beginning on day 8, patients receive oral gefitinib once daily. Beginning on day 22, patients receive oral everolimus once daily. Both drugs are then given concurrently for the rest of the treatment. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

* Phase II: Patients receive oral everolimus at the MTD determined in phase I and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following stage criteria:

  * Stage IIIB (unresectable, with malignant pleural or pericardial effusion)
  * Stage IV disease
  * Recurrent disease
* Measurable or evaluable indicator lesions
* Progressive disease after receiving ≥ 1 prior chemotherapy regimen that included cisplatin or carboplatin and docetaxel
* No uncontrolled brain or leptomeningeal metastases

  * Must not require concurrent glucocorticoids for control of metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Karnofsky 70-100% OR
* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* WBC ≥ 3,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9.0 g/dL

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST ≤ 2.5 times ULN

Renal

* Creatinine ≤ 1.5 times ULN OR
* Creatinine clearance ≥ 60 mL/min

Cardiovascular

* No congestive heart failure
* No New York Heart Association class III or IV heart disease
* No unstable angina

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No severe infection
* No severe malnutrition
* No other serious medical illness
* No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent biologic therapy
* No concurrent immunotherapy

Chemotherapy

* See Disease Characteristics
* No prior conventional chemotherapy for metastatic or recurrent NSCLC (phase II only)
* At least 4 weeks since prior chemotherapy
* No other concurrent chemotherapy

Endocrine therapy

* See Disease Characteristics
* No concurrent oral steroids for management of skin toxicity

Radiotherapy

* At least 4 weeks since prior radiotherapy
* No concurrent radiotherapy

Surgery

* At least 4 weeks since prior major surgery
* No concurrent surgery for an identifiable lesion

Other

* Recovered from all prior therapy
* No prior gefitinib, erlotinib, or other epidermal growth factor tyrosine kinase inhibitor
* No concurrent cytotoxic therapy (e.g., methotrexate for rheumatoid arthritis)
* No other concurrent oncolytic agents

Primary outcomes:
measure: Overall Objective Response
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Vincent A. Miller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Price KA, Azzoli CG, Krug LM, Pietanza MC, Rizvi NA, Pao W, Kris MG, Riely GJ, Heelan RT, Arcila ME, Miller VA. Phase II trial of gefitinib and everolimus in advanced non-small cell lung cancer. J Thorac Oncol. 2010 Oct;5(10):1623-9. doi: 10.1097/JTO.0b013e3181ec1531.