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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00096486
First received: November 9, 2004
Last updated: April 26, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: everolimus
Drug: gefitinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of everolimus [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 73
Study Start Date: May 2004
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00096486

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Vincent A. Miller, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00096486     History of Changes
Other Study ID Numbers: 04-033, MSKCC-04033
Study First Received: November 9, 2004
Last Updated: April 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Everolimus
Gefitinib
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014