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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00408460
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 34
• Locations: 2
• Arm: 1
• Duration (Months): 80
• Patients Per Site: 17
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Malignant Pleural Effusion; Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer	Drug: imatinib mesylate; Drug: paclitaxel	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

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

2. 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 Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Intermittent Gleevec® (Imatinib Mesylate) and Weekly Paclitaxel in Patients Aged 70 or Older With Advanced Non-Small Cell Lung Cancer
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (enzyme inhibitor, chemotherapy) 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.	Drug: imatinib mesylate; Given PO; Other Names: CGP 57148 Gleevec Glivec ; Drug: paclitaxel; Given IV; Other Names: Anzatax Asotax TAX Taxol

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. Overall Survival [Every 3 months for 5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
2	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Renato Martins, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Renato Martins, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT00408460
• Other Study ID Numbers: 6137; NCI-2010-00420
• First Posted: Dec 7, 2006
• Last Update Posted: Apr 25, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pleural Effusion, Malignant; Pleural Effusion; Paclitaxel; Imatinib Mesylate

Study Results

Participant Flow

Recruitment Details	Patients that were aged 70 years and above that had never received treatment for metastatic NSCLC were approached for study participation.

Arm/Group Title	Treatment (Enzyme Inhibitor, Chemotherapy)
Arm/Group Description	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. imatinib mesylate: Given PO paclitaxel: Given IV immunohistochemistry staining method: Optional correlative studies
Period Title: Overall Study
STARTED	34
COMPLETED	34
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Enzyme Inhibitor, Chemotherapy)
Arm/Group Description	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. imatinib mesylate: Given PO paclitaxel: Given IV immunohistochemistry staining method: Optional correlative studies
Overall Participants	34
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	34 100%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	75
Sex: Female, Male (Count of Participants)
Female	11 32.4%
Male	23 67.6%
Region of Enrollment (participants) [Number]
United States	34 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (Complete and Partial Responses) as Assessed by RECIST Criteria
Description	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
Time Frame	Baseline, Week 4 of courses 2, 4 and 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Chemotherapy)
Arm/Group Description	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. imatinib mesylate: Given PO paclitaxel: Given IV immunohistochemistry staining method: Optional correlative studies
Measure Participants	34
Count of Participants [Participants]	11 32.4%

2. Secondary Outcome

Title	Time to Tumor Progression
Description	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
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Chemotherapy)
Arm/Group Description	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. imatinib mesylate: Given PO paclitaxel: Given IV immunohistochemistry staining method: Optional correlative studies
Measure Participants	34
Median (Full Range) [months]	3.6

3. Secondary Outcome

Title	Overall Survival
Time Frame	Every 3 months for 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Chemotherapy)
Arm/Group Description	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. imatinib mesylate: Given PO paclitaxel: Given IV immunohistochemistry staining method: Optional correlative studies
Measure Participants	34
Median (Full Range) [months]	7.3

Adverse Events

Time Frame	Adverse events were collected from the first dose of imatinib mesylate through to the last dose of imatinib mesylate, an average of 6 months.
Adverse Event Reporting Description	Only grade 3 and higher adverse events were collected with the following exceptions. Any grade neuropathy or edema and any other adverse event that required a dose reduction or dose delay.
Arm/Group Title	Treatment (Enzyme Inhibitor, Chemotherapy)
Arm/Group Description	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. imatinib mesylate: Given PO paclitaxel: Given IV immunohistochemistry staining method: Optional correlative studies
All Cause Mortality
	Treatment (Enzyme Inhibitor, Chemotherapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Enzyme Inhibitor, Chemotherapy)
	Affected / at Risk (%)	# Events
Total	14/34 (41.2%)
Blood and lymphatic system disorders
febrile neutropenia	1/34 (2.9%)	1
Cardiac disorders
cardiac arrest	3/34 (8.8%)	3
CHF exacerbation	1/34 (2.9%)	1
Gastrointestinal disorders
Ileus	1/34 (2.9%)	1
Constipation	1/34 (2.9%)	1
Dehydration	1/34 (2.9%)	1
Diverticulitis	1/34 (2.9%)	1
Infections and infestations
Infection	3/34 (8.8%)	3
Renal and urinary disorders
Bladder Stone	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
pneumonitis	1/34 (2.9%)	1
pneumothorax	1/34 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Enzyme Inhibitor, Chemotherapy)
	Affected / at Risk (%)	# Events
Total	26/34 (76.5%)
Blood and lymphatic system disorders
anemia	3/34 (8.8%)	3
leukopenia	4/34 (11.8%)	4
neutropenia	7/34 (20.6%)	7
thrombocytopenia	1/34 (2.9%)	1
Cardiac disorders
Left ventricular systolic dysfunction	1/34 (2.9%)	1
Gastrointestinal disorders
Dehydration	1/34 (2.9%)	1
Gastroenteritis	1/34 (2.9%)	1
Anorexia	1/34 (2.9%)	1
Constipation	1/34 (2.9%)	1
Diarrhea	1/34 (2.9%)	1
Mucositis	1/34 (2.9%)	1
General disorders
Fatigue	14/34 (41.2%)	14
Edema	8/34 (23.5%)	8
Metabolism and nutrition disorders
hypophosphatemia	3/34 (8.8%)	3
Nervous system disorders
Foot Drop	1/34 (2.9%)	1
Neuropathy	10/34 (29.4%)	10
Syncope	1/34 (2.9%)	1
increased pain	1/34 (2.9%)	1
Renal and urinary disorders
acute kidney injury	4/34 (11.8%)	4
Kidney stone	1/34 (2.9%)	1
Urinary tract infection	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
pleural effusion	1/34 (2.9%)	1
pneumonia	1/34 (2.9%)	1
pulmonary edema	1/34 (2.9%)	1
Pulmonary embolism	1/34 (2.9%)	1
Skin and subcutaneous tissue disorders
Rash	3/34 (8.8%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.