Gefitinib and Everolimus in Treating Patients With Stage IIIB or Stage IV or Recurrent Non-Small Cell Lung Cancer

A Phase I/II Trial of Fixed Doses of Daily Gefitinib With Escalating Doses of Daily RAD001 in Advanced Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: everolimus; Drug: gefitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gefitinib and Everolimus (RAD001); 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.

Drug: everolimus; Drug: gefitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Objective Response	Determine efficacy of the combination oral daily gefitinib and oral daily RAD001 in patients with advanced NSCLC. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST).	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Vincent A. Miller, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 9, 2004
• First Posted (Estimate): November 10, 2004

Study Record Updates

• Last Update Posted (Estimate): January 21, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gefitinib; Everolimus
• Other Study ID Numbers: 04-033; MSKCC-04033