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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

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00096486
Enrollment
74
Registered
2004-11-10
Start date
2004-05-31
Completion date
2010-07-31
Last updated
2016-01-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer

Keywords

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

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.

Interventions

DRUGeverolimus
DRUGgefitinib

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Memorial Sloan Kettering Cancer Center
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frameDescription
Overall Objective Response2 yearsDetermine 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).

Countries

United States

Participant flow

Participants by arm

ArmCount
Phase I: RAD001 10 mg, Gefitinib 250 mg
Phase I: RAD001 10 mg, Gefitinib 250 mg
4
Phase I: RAD001 5 mg, Gefitinib 250 mg
Phase I: RAD001 5 mg, Gefitinib 250 mg
6
Phase II: Cohort I no Prior Conventional Chemotherapy
Phase II: Cohort I no prior conventional chemotherapy
26
Phase II: Cohort II One or More Prior Chemotherapy
Phase II: Cohort II one or more prior chemotherapy
38
Total74

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall StudyNot Treated0011
Overall StudyWithdrawal by Subject0011

Baseline characteristics

CharacteristicPhase I: RAD001 10 mg, Gefitinib 250 mgPhase I: RAD001 5 mg, Gefitinib 250 mgPhase II: Cohort I no Prior Conventional ChemotherapyPhase II: Cohort II One or More Prior ChemotherapyTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
3 Participants2 Participants18 Participants15 Participants38 Participants
Age, Categorical
Between 18 and 65 years
1 Participants4 Participants8 Participants23 Participants36 Participants
Sex: Female, Male
Female
2 Participants2 Participants10 Participants22 Participants36 Participants
Sex: Female, Male
Male
2 Participants4 Participants16 Participants16 Participants38 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
3 / 45 / 620 / 2628 / 38
serious
Total, serious adverse events
1 / 42 / 65 / 2615 / 38

Outcome results

Primary

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

ArmMeasureGroupValue (NUMBER)
Phase I: RAD001 10 mg, Gefitinib 250 mgOverall Objective ResponsePartial Response (PR)1 participants
Phase I: RAD001 10 mg, Gefitinib 250 mgOverall Objective ResponseStable Disease (SD)1 participants
Phase I: RAD001 10 mg, Gefitinib 250 mgOverall Objective ResponseProgression of Disease (POD)1 participants
Phase I: RAD001 10 mg, Gefitinib 250 mgOverall Objective ResponseNot Evaluable/ Evaluable for Toxicity Only1 participants
Phase I: RAD001 5 mg, Gefitinib 250 mgOverall Objective ResponseStable Disease (SD)1 participants
Phase I: RAD001 5 mg, Gefitinib 250 mgOverall Objective ResponseProgression of Disease (POD)4 participants
Phase I: RAD001 5 mg, Gefitinib 250 mgOverall Objective ResponseNot Evaluable/ Evaluable for Toxicity Only0 participants
Phase I: RAD001 5 mg, Gefitinib 250 mgOverall Objective ResponsePartial Response (PR)1 participants
Phase II: Cohort I no Prior Conventional ChemotherapyOverall Objective ResponseProgression of Disease (POD)11 participants
Phase II: Cohort I no Prior Conventional ChemotherapyOverall Objective ResponseStable Disease (SD)9 participants
Phase II: Cohort I no Prior Conventional ChemotherapyOverall Objective ResponseNot Evaluable/ Evaluable for Toxicity Only1 participants
Phase II: Cohort I no Prior Conventional ChemotherapyOverall Objective ResponsePartial Response (PR)3 participants
Phase II: Cohort II One or More Prior ChemotherapyOverall Objective ResponseNot Evaluable/ Evaluable for Toxicity Only1 participants
Phase II: Cohort II One or More Prior ChemotherapyOverall Objective ResponseStable Disease (SD)15 participants
Phase II: Cohort II One or More Prior ChemotherapyOverall Objective ResponsePartial Response (PR)2 participants
Phase II: Cohort II One or More Prior ChemotherapyOverall Objective ResponseProgression of Disease (POD)18 participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026