Imatinib Mesylate and Paclitaxel in Treating Older Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Phase 2

Completed

• Conditions: Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Malignant Pleural Effusion; Stage IV Non-small Cell Lung Cancer
• Interventions: Drug: imatinib mesylate; Drug: paclitaxel

• Registration Number: NCT00408460
• Lead Sponsor: University of Washington

Brief Summary

This phase II trial is studying how well giving imatinib mesylate together with paclitaxel works in treating older patients with stage IIIB or stage IV non-small cell lung cancer. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with paclitaxel may kill more tumor cells

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the clinical efficacy of the combination of weekly paclitaxel and intermittent imatinib in elderly patients with advanced non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of the combination of weekly paclitaxel and intermittent imatinib in elderly patients with advanced non-small cell lung cancer.

II. To collect paraffin tissue blocks for a companion project evaluating the expression of platelet derived growth factor (PDGF) by original tumor specimens, and its relationship to response rate and survival.

OUTLINE:

Patients receive paclitaxel intravenously (IV) on days 3, 10, and 17 and imatinib mesylate orally (PO) once daily (QD) on days 1-4, 8-11, and 15-18. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Timeline

• Study Start: 2006-02
• Study First Submitted: 2006-12-06
• Study First Submitted QC: 2006-12-06
• Study First Posted: 2006-12-07
• Primary Completion: 2010-08
• Study Completion: 2012-10
• Status Verified: 2017-01
• Results First Submitted: 2017-01-17
• Results First Submitted QC: 2017-03-13
• Last Update Submitted: 2017-03-13
• Results First Posted: 2017-04-25
• Last Update Posted: 2017-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Histologic or cytologic diagnosis of non-small cell lung cancer
• At least one site of measurable disease, as defined by the modified RECIST criteria
• Stage IIIB with pleural effusion or Stage IV disease; includes patients who received surgery alone for early stage disease, now in relapse with advanced disease; staging is according to the American Joint Committee on Cancer classification scheme, 6th edition
• Total bilirubin < 1.25 x upper limit of normal (ULN)
• Baseline absolute neutrophil count >= 1500/uL
• Baseline platelet count >= 100,000/uL
• ECOG Performance Status 0, 1 or 2 at the time of informed consent
• Written, voluntary consent
• Patients with reproductive potential must use an acceptable contraceptive method, such methods include: 1) Male hormonal contraception; 2) Partner without reproductive potential, including post-menopausal status or history of tubal ligation; 3) Partner with intrauterine device (IUD) or contraceptive vaginal ring; 4) Partner takes oral contraceptive pill, wears contraceptive patch, or has contraceptive implant; 5) Routine use of barrier method, such as condoms or diaphragm, during sexual intercourse
• AST and ALT =< 2.5 x ULN
• Creatinine =< 1.5 x ULN

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Exclusion Criteria

• Uncontrolled brain metastasis; patients with known brain metastasis must have completed treatment with surgery, radiation or both; in addition, they must be off corticosteroids
• Symptomatic neuropathy (Grade 2 or higher)
• Prior chemotherapy for advanced non-small cell lung cancer (Prior adjuvant, neoadjuvant, or chemoradiotherapy for NSCLC is permitted, provided at least 6 months elapsed prior to documented metastatic recurrence)
• Patient is < 5 years free of another primary malignancy, except: a) if the other malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other primary malignancy is not considered clinically significant and is requiring no active intervention
• Prior radiation therapy to > 25% of bone marrow
• Grade III/IV congestive heart failure, as defined by NYHA criteria, or myocardial infarction within 6 months
• Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study
• Patient has known chronic liver disease, e.g., diagnosis of chronic active hepatitis or cirrhosis
• Major surgery two weeks prior to study treatment
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent
• Any condition requiring continuous administration of systemic corticosteroids
• The patient is on therapeutic anti-coagulation with warfarin
• The administration of any other anticancer agents including chemotherapy and biologic agents is NOT permitted
• The use of other concurrent investigational drugs is not allowed
• Participants in this study must avoid grapefruit juice or other grapefruit-containing products for the duration of treatment with imatinib

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (enzyme inhibitor, chemotherapy)	imatinib mesylate	Patients receive paclitaxel IV on days 3, 10, and 17 and imatinib mesylate PO QD on days 1-4, 8-11, and 15-18. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.
Treatment (enzyme inhibitor, chemotherapy)	paclitaxel	Patients receive paclitaxel IV on days 3, 10, and 17 and imatinib mesylate PO QD on days 1-4, 8-11, and 15-18. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (Complete and Partial Responses) as Assessed by RECIST Criteria	Baseline, Week 4 of courses 2, 4 and 6	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Every 3 months for 5 years
Time to Tumor Progression	Baseline and every 2 months post treatment until the date of first documented tumor progression or date of death from any cause, whichever came first, assessed up to 5 years.	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Trial Locations

Locations (2)

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States