E7389 in Treating Patients With Recurrent or Progressive Stage IIIB or Stage IV Non-Small Cell Lung Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00400829
• Collaborator: (none)
• Enrollment: 66
• Locations: 2
• Arm: 1
• Duration (Months): 50
• Patients Per Site: 33
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This phase II trial is studying how well E7389 works in treating patients with recurrent or progressive stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as E7389, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer	Drug: eribulin mesylate	Phase 2

Detailed Description

OBJECTIVES:

1. Evaluate the antitumor activity of E7389 (eribulin mesylate), in terms of objective response rate, in patients with recurrent or progressive stage IIIB or IV non-small cell lung cancer.

2. Evaluate the time to progression and overall survival of patients treated with this drug.

3. Evaluate the toxicity profile of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed once monthly for at least 6 months and then periodically thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Halichondrin B Analog E7389 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Previously Treated With a Taxane
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive 1.4 mg/m2 eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: eribulin mesylate; Given IV; Other Names: B1939 E7389 ER-086526 halichrondrin B analog

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (CR or PR) According to RECIST Criteria [Tumor measurements repeated every 6 weeks]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT, MRI or X-ray: 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. Overall Survival [From start of treatment to death from any cause, assessed up to 5 years]

   Will be estimated using the product-limit method of Kaplan and Meier.

2. Progression Free Survival [From start of treatment to the time of documented progression, assessed up to 5 years]

   Will be estimated using the product-limit method of Kaplan and Meier.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

• Stage IIIB or IV disease

• Recurrent or progressive disease

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Must have received prior treatment with platinum-based therapy and a taxane

• Asymptomatic brain metastasis allowed provided off steroids for > 2 weeks

• Zubrod performance status (PS) ≤ 2 OR Karnofsky PS 60-100%

• Life expectancy > 3 months

• Platelet count ≥ 100,000/mm³

• Bilirubin ≤ 2.0 mg/dL

• AST/ALT ≤ 2.5 times upper limit of normal

• Creatinine normal OR creatinine clearance ≥ 50 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No neuropathy ≥ grade 2

• No uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situations that would preclude study compliance

• No other concurrent investigational agents

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered

• At least 2 weeks since prior radiotherapy, including palliative radiotherapy, and recovered

• No more than 2 prior chemotherapy regimens for NSCLC in the metastatic or adjuvant setting

• No concurrent combination antiretroviral therapy for HIV-positive patients

Exclusion Criteria:

• Absolute neutrophil count ≥ 1,500/mm³

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to E7389

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Barbara Gitlitz, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00400829
• Other Study ID Numbers: NCI-2009-01159; NCI-2009-01159; CDR0000514516; PHII-74; 7437; N01CM62204; N01CM62201; N01CM62209
• First Posted: Nov 17, 2006
• Last Update Posted: Jan 7, 2015
• Last Verified: Oct 1, 2013

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Arm/Group Title	Arm I
Arm/Group Description	Patients receive 1.4 mg/m2 eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. eribulin mesylate: Given IV
Period Title: Overall Study
STARTED	66
COMPLETED	66
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	Patients receive 1.4 mg/m2 eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. eribulin mesylate: Given IV
Overall Participants	66
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	35 53%
Male	31 47%
Region of Enrollment (participants) [Number]
United States	66 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (CR or PR) According to RECIST Criteria
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT, MRI or X-ray: 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	Tumor measurements repeated every 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive 1.4 mg/m2 eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. eribulin mesylate: Given IV
Measure Participants	66
Number [percentage of patients responding]	5

2. Secondary Outcome

Title	Overall Survival
Description	Will be estimated using the product-limit method of Kaplan and Meier.
Time Frame	From start of treatment to death from any cause, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive 1.4 mg/m2 eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. eribulin mesylate: Given IV
Measure Participants	66
Median (95% Confidence Interval) [Months]	11.6

3. Secondary Outcome

Title	Progression Free Survival
Description	Will be estimated using the product-limit method of Kaplan and Meier.
Time Frame	From start of treatment to the time of documented progression, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive 1.4 mg/m2 eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. eribulin mesylate: Given IV
Measure Participants	66
Median (95% Confidence Interval) [Months]	2.7

Adverse Events

Time Frame	Adverse Events were recorded over a 40 month period.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Arm I
Arm/Group Description	Patients receive eribulin mesylate IV over 1-2 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. eribulin mesylate: Given IV
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	23/66 (34.8%)
Blood and lymphatic system disorders
Febrile neutropenia	1/66 (1.5%)	1
Hemoglobin decreased	1/66 (1.5%)	1
Endocrine disorders
Adrenal insufficiency	1/66 (1.5%)	1
Gastrointestinal disorders
Abdominal pain	1/66 (1.5%)	1
Constipation	3/66 (4.5%)	3
Nausea	3/66 (4.5%)	3
Vomiting	1/66 (1.5%)	1
General disorders
Death	2/66 (3%)	2
Disease progression	1/66 (1.5%)	1
Fatigue	3/66 (4.5%)	3
Fever	1/66 (1.5%)	1
Immune system disorders
Hypersensitivity	1/66 (1.5%)	1
Infections and infestations
Laryngitis	1/66 (1.5%)	1
Investigations
Leukocyte count decreased	2/66 (3%)	3
Leukopenia	1/66 (1.5%)	1
Neutrophil count decreased	13/66 (19.7%)	19
Metabolism and nutrition disorders
Anorexia	2/66 (3%)	2
Dehydration	1/66 (1.5%)	1
Serum sodium decreased	1/66 (1.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/66 (1.5%)	1
Nervous system disorders
Depressed level of consciousness	1/66 (1.5%)	1
Intracranial hemorrhage	1/66 (1.5%)	1
Psychiatric disorders
Insomnia	1/66 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/66 (3%)	2
Dyspnea	2/66 (3%)	2
Hypoxia	1/66 (1.5%)	1
Pneumonitis	1/66 (1.5%)	1
Skin and subcutaneous tissue disorders
Pain of skin	1/66 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	65/66 (98.5%)
Blood and lymphatic system disorders
Hemoglobin decreased	46/66 (69.7%)	159
Cardiac disorders
Cardiac disorder	1/66 (1.5%)	1
Left ventricular failure	1/66 (1.5%)	1
Palpitations	1/66 (1.5%)	1
Pericardial effusion	1/66 (1.5%)	1
Sinus tachycardia	3/66 (4.5%)	4
Ear and labyrinth disorders
Hearing loss	1/66 (1.5%)	1
Eye disorders
Dry eye syndrome	1/66 (1.5%)	1
Extraocular muscle paresis	1/66 (1.5%)	3
Eye disorder	1/66 (1.5%)	2
Vision blurred	3/66 (4.5%)	4
Watering eyes	2/66 (3%)	7
Gastrointestinal disorders
Abdominal distension	1/66 (1.5%)	1
Abdominal pain	10/66 (15.2%)	14
Ascites	1/66 (1.5%)	1
Constipation	17/66 (25.8%)	29
Diarrhea	7/66 (10.6%)	18
Dyspepsia	7/66 (10.6%)	11
Dysphagia	2/66 (3%)	3
Ear, nose and throat examination abnormal	8/66 (12.1%)	10
Esophageal pain	1/66 (1.5%)	1
Gastritis	1/66 (1.5%)	1
Gastrointestinal disorder	2/66 (3%)	3
Mucositis oral	2/66 (3%)	2
Nausea	16/66 (24.2%)	28
Oral hemorrhage	1/66 (1.5%)	1
Oral pain	1/66 (1.5%)	1
Vomiting	8/66 (12.1%)	8
General disorders
Chest pain	9/66 (13.6%)	14
Chills	2/66 (3%)	4
Death	11/66 (16.7%)	11
Disease progression	30/66 (45.5%)	30
Edema limbs	11/66 (16.7%)	25
Fatigue	45/66 (68.2%)	137
Fever	9/66 (13.6%)	14
Gait abnormal	1/66 (1.5%)	1
General symptom	4/66 (6.1%)	14
Injection site reaction	1/66 (1.5%)	2
Localized edema	1/66 (1.5%)	6
Pain	7/66 (10.6%)	10
Hepatobiliary disorders
Hepatic pain	2/66 (3%)	4
Infections and infestations
Bronchitis	5/66 (7.6%)	5
Catheter related infection	1/66 (1.5%)	1
Eye infection	1/66 (1.5%)	1
Infection	1/66 (1.5%)	14
Paranasal sinus infection	1/66 (1.5%)	2
Pneumonia	2/66 (3%)	3
Sinusitis	2/66 (3%)	2
Skin infection	1/66 (1.5%)	1
Upper respiratory infection	1/66 (1.5%)	1
Urinary tract infection	3/66 (4.5%)	3
Investigations
Activated partial thromboplastin time prolonged	1/66 (1.5%)	2
Alanine aminotransferase increased	11/66 (16.7%)	31
Alkaline phosphatase increased	12/66 (18.2%)	43
Aspartate aminotransferase increased	15/66 (22.7%)	25
Bilirubin increased	5/66 (7.6%)	5
Creatinine increased	2/66 (3%)	3
Forced expiratory volume decreased	1/66 (1.5%)	1
INR increased	2/66 (3%)	7
Laboratory test abnormal	2/66 (3%)	4
Leukocyte count decreased	38/66 (57.6%)	147
Leukopenia	4/66 (6.1%)	6
Lymphocyte count decreased	27/66 (40.9%)	104
Neutrophil count decreased	38/66 (57.6%)	126
Platelet count decreased	7/66 (10.6%)	10
Serum cholesterol increased	2/66 (3%)	4
Weight loss	4/66 (6.1%)	6
Metabolism and nutrition disorders
Anorexia	24/66 (36.4%)	49
Blood bicarbonate decreased	4/66 (6.1%)	7
Blood glucose increased	31/66 (47%)	84
Dehydration	4/66 (6.1%)	11
Hyperglycemia	1/66 (1.5%)	1
Hypoalbuminemia	2/66 (3%)	2
Serum albumin decreased	20/66 (30.3%)	48
Serum calcium decreased	6/66 (9.1%)	7
Serum calcium increased	6/66 (9.1%)	8
Serum glucose decreased	4/66 (6.1%)	5
Serum magnesium decreased	5/66 (7.6%)	10
Serum magnesium increased	1/66 (1.5%)	1
Serum phosphate decreased	7/66 (10.6%)	13
Serum potassium decreased	9/66 (13.6%)	13
Serum potassium increased	4/66 (6.1%)	6
Serum sodium decreased	12/66 (18.2%)	23
Serum sodium increased	1/66 (1.5%)	1
Serum triglycerides increased	2/66 (3%)	4
Musculoskeletal and connective tissue disorders
Back pain	10/66 (15.2%)	37
Bone pain	6/66 (9.1%)	10
Chest wall pain	7/66 (10.6%)	20
Joint disorder	1/66 (1.5%)	2
Joint pain	8/66 (12.1%)	22
Muscle weakness	6/66 (9.1%)	8
Muscle weakness lower limb	1/66 (1.5%)	1
Musculoskeletal disorder	3/66 (4.5%)	5
Myalgia	12/66 (18.2%)	26
Neck pain	2/66 (3%)	2
Pain in extremity	11/66 (16.7%)	22
Nervous system disorders
Acoustic nerve disorder NOS	1/66 (1.5%)	1
Ataxia	1/66 (1.5%)	7
Cognitive disturbance	1/66 (1.5%)	1
Depressed level of consciousness	1/66 (1.5%)	1
Dizziness	11/66 (16.7%)	15
Headache	10/66 (15.2%)	15
Neuralgia	1/66 (1.5%)	2
Neurological disorder NOS	2/66 (3%)	3
Peripheral motor neuropathy	2/66 (3%)	4
Peripheral sensory neuropathy	27/66 (40.9%)	67
Seizure	1/66 (1.5%)	1
Syncope	2/66 (3%)	2
Taste alteration	2/66 (3%)	7
Tremor	1/66 (1.5%)	2
Psychiatric disorders
Anxiety	6/66 (9.1%)	20
Confusion	2/66 (3%)	2
Depression	5/66 (7.6%)	8
Insomnia	6/66 (9.1%)	9
Renal and urinary disorders
Glomerular filtration rate decreased	1/66 (1.5%)	3
Hemorrhage urinary tract	1/66 (1.5%)	1
Protein urine positive	3/66 (4.5%)	4
Urethral pain	1/66 (1.5%)	1
Urinary frequency	1/66 (1.5%)	2
Urinary incontinence	1/66 (1.5%)	1
Reproductive system and breast disorders
Testicular pain	1/66 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	5/66 (7.6%)	13
Bronchial obstruction	1/66 (1.5%)	1
Bronchopulmonary hemorrhage	1/66 (1.5%)	1
Bronchospasm	5/66 (7.6%)	14
Cough	28/66 (42.4%)	56
Dyspnea	22/66 (33.3%)	70
Hemoptysis	1/66 (1.5%)	1
Hemorrhage nasal	2/66 (3%)	2
Laryngeal pain	1/66 (1.5%)	1
Nasal congestion	2/66 (3%)	3
Pharyngolaryngeal pain	1/66 (1.5%)	1
Pleural effusion	1/66 (1.5%)	1
Pleuritic pain	1/66 (1.5%)	1
Pneumonitis	1/66 (1.5%)	1
Respiratory disorder	3/66 (4.5%)	6
Respiratory tract hemorrhage	2/66 (3%)	2
Voice alteration	4/66 (6.1%)	12
Skin and subcutaneous tissue disorders
Alopecia	14/66 (21.2%)	54
Dry skin	2/66 (3%)	7
Nail disorder	1/66 (1.5%)	5
Rash acneiform	1/66 (1.5%)	1
Rash desquamating	6/66 (9.1%)	7
Sweating	2/66 (3%)	2
Vascular disorders
Flushing	1/66 (1.5%)	2
Hypertension	2/66 (3%)	2
Hypotension	3/66 (4.5%)	6
Phlebitis	1/66 (1.5%)	5
Thrombosis	1/66 (1.5%)	6
Vascular disorder	2/66 (3%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.