CompletedNCT00096486Updated Jan 21, 2016Results posted

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

A Phase 1/2 interventional study of everolimus and gefitinib in Lung Cancer, sponsored by Memorial Sloan Kettering Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2016-01-21.

Sponsored by Memorial Sloan Kettering Cancer Center · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 74
Allocation: Not applicable
Ages: 18 Years to 120 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Lung Cancer

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Keywords

recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 74 is above the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

Memorial Sloan Kettering Cancer Center is the lead sponsor of 1,930 studies on the registry; 328 are open to participants now.

Of its 129 completed or terminated interventional studies of FDA-regulated products, 66 (51%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 120 Years
Sexes eligible: All
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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 74 participants (actual)

Study arms

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

Interventions

Drugeverolimus
Druggefitinib

What researchers measure

Primary outcomes

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).
Time frame: 2 years

Results

Posted Jan 21, 2016

Participant flow

Participant flow — Overall Study
Milestone	Phase I: RAD001 10 mg, Gefitinib 250 mg	Phase I: RAD001 5 mg, Gefitinib 250 mg	Phase II: Cohort I no Prior Conventional Chemotherapy	Phase II: Cohort II One or More Prior Chemotherapy
Started	4	6	26	38
Completed	4	6	24	36
Not completed	0	0	2	2
Withdrew: Withdrawal by subject	0	0	1	1
Withdrew: Not treated	0	0	1	1

Outcome measures

PrimaryOverall 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).

Time frame:: 2 years
Reported as:: Number · participants

Overall Objective Response
participants	Phase I: RAD001 10 mg, Gefitinib 250 mg	Phase I: RAD001 5 mg, Gefitinib 250 mg	Phase II: Cohort I no Prior Conventional Chemotherapy	Phase II: Cohort II One or More Prior Chemotherapy
Partial Response (PR)	1	1	3	2
Stable Disease (SD)	1	1	9	15
Progression of Disease (POD)	1	4	11	18
Not Evaluable/ Evaluable for Toxicity Only	1	0	1	1

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase I: RAD001 10 mg, Gefitinib 250 mg	—	1/4 (25%)	3/4 (75%)
Phase I: RAD001 5 mg, Gefitinib 250 mg	—	2/6 (33.3%)	5/6 (83.3%)
Phase II: Cohort I no Prior Conventional Chemotherapy	—	5/26 (19.2%)	20/26 (76.9%)
Phase II: Cohort II One or More Prior Chemotherapy	—	15/38 (39.5%)	28/38 (73.7%)

Most frequent serious events

Showing 10 of 24

Most frequent serious events
Event	Phase I: RAD001 10 mg, Gefitinib 250 mg	Phase I: RAD001 5 mg, Gefitinib 250 mg	Phase II: Cohort I no Prior Conventional Chemotherapy	Phase II: Cohort II One or More Prior Chemotherapy
Death not associated with CTCAE term- Multi-organ failureGeneral disorders	1/4	0/6	0/26	0/38
Pain - Extremity-limbGeneral disorders	0/4	1/6	0/26	0/38
Thrombosis/embolism (vascular access-related)Respiratory, thoracic and mediastinal disorders	0/4	1/6	0/26	1/38
DiarrheaGastrointestinal disorders	0/4	0/6	0/26	3/38
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders	0/4	0/6	2/26	2/38
NauseaGastrointestinal disorders	0/4	0/6	0/26	2/38
Pain - BackGeneral disorders	0/4	0/6	1/26	2/38
Hemorrhage, Upper GI NOSGastrointestinal disorders	0/4	0/6	1/26	0/38
Hemorrhage/Bleeding, otherBlood and lymphatic system disorders	0/4	0/6	1/26	0/38
HypoxiaRespiratory, thoracic and mediastinal disorders	0/4	0/6	1/26	0/38

Most frequent other events

Showing 10 of 13

Most frequent other events
Event	Phase I: RAD001 10 mg, Gefitinib 250 mg	Phase I: RAD001 5 mg, Gefitinib 250 mg	Phase II: Cohort I no Prior Conventional Chemotherapy	Phase II: Cohort II One or More Prior Chemotherapy
Fatigue (asthenia, lethargy, malaise)General disorders	1/4	3/6	7/26	15/38
Mucositis (Clincal exam)- Oral cavityGeneral disorders	1/4	0/6	13/26	14/38
Rash/desquamationSkin and subcutaneous tissue disorders	1/4	0/6	8/26	14/38
AnorexiaGeneral disorders	1/4	0/6	0/26	4/38
ConstipationGastrointestinal disorders	1/4	0/6	0/26	0/38
DiarrheaGastrointestinal disorders	1/4	0/6	5/26	4/38
INRBlood and lymphatic system disorders	1/4	0/6	3/26	0/38
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders	0/4	1/6	2/26	6/38
LymphopeniaBlood and lymphatic system disorders	0/4	1/6	0/26	6/38
Mucositis (symptoms)- Oral cavityGeneral disorders	0/4	1/6	0/26	0/38

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Phase I: RAD001 10 mg, Gefitinib 250 mg	Phase I: RAD001 5 mg, Gefitinib 250 mg	Phase II: Cohort I no Prior Conventional Chemotherapy	Phase II: Cohort II One or More Prior Chemotherapy	Total
<=18 years	0	0	0	0	0
Between 18 and 65 years	1	4	8	23	36
>=65 years	3	2	18	15	38

Sex: Female, Male
Sex: Female, Male(Participants)	Phase I: RAD001 10 mg, Gefitinib 250 mg	Phase I: RAD001 5 mg, Gefitinib 250 mg	Phase II: Cohort I no Prior Conventional Chemotherapy	Phase II: Cohort II One or More Prior Chemotherapy	Total
Female	2	2	10	22	36
Male	2	4	16	16	38

Study locations

1 site

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

References and documents

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. PubMed 20871262 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 21, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00096486
Lead sponsor: Memorial Sloan Kettering Cancer Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Nov 10, 2004
Start date: May 2004
Primary completion: Jul 2010
Completion: Jul 2010
Results posted: Jan 21, 2016
Last update: Jan 21, 2016

Study contacts

Vincent A. Miller, MD

principal investigator · Memorial Sloan Kettering Cancer Center

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2015. You cannot join it, but the record below documents what was studied.

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