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

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
everolimus
gefitinib
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gefitinib and Everolimus (RAD001)

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Full Information

First Posted
November 9, 2004
Last Updated
December 15, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00096486
Brief Title
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

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gefitinib and Everolimus (RAD001)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
everolimus
Intervention Type
Drug
Intervention Name(s)
gefitinib
Primary Outcome Measure Information:
Title
Overall Objective Response
Description
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).
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincent A. Miller, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20871262
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.
Results Reference
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Gefitinib and Everolimus in Treating Patients With Stage IIIB or Stage IV or Recurrent Non-Small Cell Lung Cancer

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