Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00118144
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arm: 1
• Duration (Months): 66
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This phase II trial is studying how well bortezomib works in treating patients with stage IIIB or stage IV lung cancer. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Lung; Bronchoalveolar Cell Lung Cancer; Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer	Drug: bortezomib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the objective response rate in patients with stage IIIB or IV bronchoalveolar carcinoma (BAC) or adencarcinoma of the lung with BAC features treated with bortezomib.

SECONDARY OBJECTIVES:

1. Determine the progression-free and overall survival of patients treated with this drug.

2. Determine the time to disease progression in patients treated with this drug.

3. Determine predictors of response, based on molecular correlative studies of tumor and blood, in patients with treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to prior epidermal growth factor receptor inhibitor therapy (yes vs no).

Patients receive bortezomib IV over 3-5 seconds on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Bortezomib (PS-341) for Patients With Advanced Bronchiolo-Alveolar Carcinoma (BAC) or Adenocarcinoma With BAC Features
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive bortezomib IV over 3-5 seconds on days 1 and 8.	Drug: bortezomib; Given IV

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate With Bortezomib Evaluated by Both RECIST Criteria and Computer-assisted Image Analysis. [Up to 5 years]

   A response rate of 20% or more with bortezomib would be of interest for further evaluation, whereas a response rate of less than 5% would be of no interest. Response defined as a confirmed CR or PR.

Secondary Outcome Measures

1. Progression-free Survival [Up to 5 years]

   Progression Free Survival using the product-limit method of Kaplan and Meier

2. Overall Survival [Up to 5 years]

   Overall Suvival 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

Criteria:

• Histologically confirmed bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features:

• Stage IIIB or IV disease:

• Patients with stage IIIB disease must be ineligible for definitive combined modality treatment with radiotherapy and chemotherapy

• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan:

• Previously irradiated lesions are considered measurable only if lesion progressed after completion of radiotherapy

• No unstable brain metastases:

• Brain metastases that are stable for ≥ 1 month after completion of prior radiotherapy, stereotactic surgery, or surgery are allowed

• Performance status:

• ECOG 0-2

• Life expectancy >3 months

• Hepatic:

• Bilirubin normal

• AST and ALT =< 2.5 times upper limit of normal

• Renal:

• Creatinine normal OR creatinine clearance >= 60 mL/min

• Cardiovascular:

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmias

• No more than 1 prior chemotherapy regimen for advanced BAC:

• Prior gefitinib or other known epidermal growth factor receptor (EGFR) inhibitors are not considered a systemic chemotherapy regimen

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• At least 4 weeks since prior corticosteroids

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception before, during, and for 30 days after completion of study treatment

• No ongoing or active infection

• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is in complete remission

• No peripheral neuropathy >= grade 2

• No known hypersensitivity to bortezomib, boron, or mannitol

• No psychiatric illness or social situation that would preclude study compliance

• No other uncontrolled illness

• No concurrent routine granulocyte colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

• At least 2 weeks since prior radiotherapy

• Recovered from prior therapy (alopecia allowed)

• At least 2 weeks since prior EGFR inhibitors

• At least 4 weeks since prior anticonvulsants

• No prior bortezomib

• No concurrent antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents

• No other concurrent anticancer therapy

• Concurrent bisphosphonates for bone metastases allowed

• Hematopoietic:

• Absolute neutrophil count >= 1,500/mm3

• Platelet count >= 100,000/mm3

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Gandara, 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: NCT00118144
• Other Study ID Numbers: NCI-2009-00113; NCI-2009-00113; CDR0000433404; PHII-57; 7003; N01CM62208; N01CM62201; N01CM62209; N01CM62207
• First Posted: Jul 11, 2005
• Last Update Posted: Aug 21, 2014
• Last Verified: Apr 1, 2013

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Arm I
Arm/Group Description	Patients receive bortezomib IV at 1.6 mg/m2 on days 1 and 8 of every 21 day cycle.
Period Title: Overall Study
STARTED	42
COMPLETED	41
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Arm 1
Arm/Group Description	Patients receive bortezomib IV at 1.6 mg/m2 on days 1 and 8 of every 21 day cycle.
Overall Participants	42
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	23 54.8%
Male	19 45.2%
Region of Enrollment (participants) [Number]
United States	42 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate With Bortezomib Evaluated by Both RECIST Criteria and Computer-assisted Image Analysis.
Description	A response rate of 20% or more with bortezomib would be of interest for further evaluation, whereas a response rate of less than 5% would be of no interest. Response defined as a confirmed CR or PR.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Patients receive bortezomib IV at 1.6 mg/m2 on days 1 and 8 of every 21 day cycle.
Measure Participants	42
Number [percentage of responders]	5

2. Secondary Outcome

Title	Progression-free Survival
Description	Progression Free Survival using the product-limit method of Kaplan and Meier
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Patients receive bortezomib IV at 1.6 mg/m2 on days 1 and 8 of every 21 day cycle.
Measure Participants	42
Median (95% Confidence Interval) [Months]	5.5

3. Secondary Outcome

Title	Overall Survival
Description	Overall Suvival using the product-limit method of Kaplan and Meier.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive bortezomib IV at 1.6 mg/m2 on days 1 and 8 of every 21 day cycle. bortezomib: Given IV
Measure Participants	42
Mean (95% Confidence Interval) [Months]	13.6

Adverse Events

Arm/Group Title	Arm I
Arm/Group Description	Patients receive bortezomib IV at 1.6 mg/m2 on days 1 and 8 of every 21 day cycle.
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	12/42 (28.6%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/42 (2.4%)	1
Gastrointestinal disorders
Abdominal pain	1/42 (2.4%)	1
Constipation	1/42 (2.4%)	1
Diarrhea	1/42 (2.4%)	1
Ear, nose and throat examination abnormal	1/42 (2.4%)	1
Nausea	1/42 (2.4%)	1
Upper gastrointestinal hemorrhage	1/42 (2.4%)	1
Vomiting	2/42 (4.8%)	2
General disorders
Disease progression	4/42 (9.5%)	4
Fatigue	2/42 (4.8%)	2
Fever	1/42 (2.4%)	1
Hepatobiliary disorders
Hepatic failure	1/42 (2.4%)	1
Infections and infestations
Pneumonia	1/42 (2.4%)	2
Injury, poisoning and procedural complications
Fracture	1/42 (2.4%)	1
Investigations
Alanine aminotransferase increased	1/42 (2.4%)	1
Alkaline phosphatase increased	1/42 (2.4%)	1
Aspartate aminotransferase increased	1/42 (2.4%)	1
Bilirubin increased	1/42 (2.4%)	1
Lymphocyte count decreased	1/42 (2.4%)	1
Metabolism and nutrition disorders
Blood glucose increased	1/42 (2.4%)	1
Dehydration	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/42 (4.8%)	2
Bone pain	1/42 (2.4%)	1
Myalgia	1/42 (2.4%)	1
Pain in extremity	1/42 (2.4%)	1
Nervous system disorders
Acoustic nerve disorder NOS	1/42 (2.4%)	1
Peripheral motor neuropathy	1/42 (2.4%)	1
Seizure	1/42 (2.4%)	1
Speech disorder	1/42 (2.4%)	1
Psychiatric disorders
Anxiety	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/42 (2.4%)	1
Cough	1/42 (2.4%)	1
Dyspnea	3/42 (7.1%)	4
Hypoxia	1/42 (2.4%)	1
Pleuritic pain	1/42 (2.4%)	1
Skin and subcutaneous tissue disorders
Pruritus	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	42/42 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	15/42 (35.7%)	92
Lymphangiopathy NOS	1/42 (2.4%)	2
Cardiac disorders
Palpitations	1/42 (2.4%)	1
Sinus tachycardia	2/42 (4.8%)	4
Supraventricular tachycardia	1/42 (2.4%)	1
Endocrine disorders
Endocrine disorder	1/42 (2.4%)	1
Eye disorders
Cataract	1/42 (2.4%)	1
Dry eye syndrome	1/42 (2.4%)	2
Flashing vision	1/42 (2.4%)	3
Vision blurred	3/42 (7.1%)	9
Watering eyes	2/42 (4.8%)	2
Gastrointestinal disorders
Abdominal distension	2/42 (4.8%)	6
Abdominal pain	8/42 (19%)	13
Constipation	14/42 (33.3%)	42
Diarrhea	20/42 (47.6%)	51
Dyspepsia	3/42 (7.1%)	5
Ear, nose and throat examination abnormal	3/42 (7.1%)	3
Gastrointestinal disorder	1/42 (2.4%)	1
Mucositis oral	1/42 (2.4%)	1
Nausea	22/42 (52.4%)	48
Stomach pain	2/42 (4.8%)	2
Tooth disorder	1/42 (2.4%)	1
Toothache	2/42 (4.8%)	4
Vomiting	11/42 (26.2%)	18
General disorders
Chest pain	7/42 (16.7%)	16
Chills	1/42 (2.4%)	1
Death	3/42 (7.1%)	3
Disease progression	15/42 (35.7%)	15
Edema limbs	4/42 (9.5%)	5
Fatigue	29/42 (69%)	146
Fever	1/42 (2.4%)	1
Flu-like symptoms	1/42 (2.4%)	1
Ill-defined disorder	2/42 (4.8%)	3
Pain	6/42 (14.3%)	7
Hepatobiliary disorders
Gallbladder obstruction	1/42 (2.4%)	1
Immune system disorders
Hypersensitivity	1/42 (2.4%)	1
Infections and infestations
Bronchitis	2/42 (4.8%)	6
Conjunctivitis infective	1/42 (2.4%)	1
Lip infection	2/42 (4.8%)	3
Otitis externa	1/42 (2.4%)	1
Peripheral nerve infection	1/42 (2.4%)	1
Pharyngitis	1/42 (2.4%)	2
Sinusitis	2/42 (4.8%)	3
Upper aerodigestive tract infection	2/42 (4.8%)	3
Upper respiratory infection	2/42 (4.8%)	2
Urinary tract infection	2/42 (4.8%)	3
Injury, poisoning and procedural complications
Bruising	1/42 (2.4%)	1
Fracture	1/42 (2.4%)	4
Investigations
Activated partial thromboplastin time prolonged	1/42 (2.4%)	1
Alanine aminotransferase increased	4/42 (9.5%)	12
Alkaline phosphatase increased	5/42 (11.9%)	15
Aspartate aminotransferase increased	4/42 (9.5%)	13
Bilirubin increased	1/42 (2.4%)	2
Creatinine increased	2/42 (4.8%)	3
Hyperbilirubinemia	1/42 (2.4%)	3
INR increased	1/42 (2.4%)	1
Leukocyte count decreased	2/42 (4.8%)	11
Leukopenia	3/42 (7.1%)	25
Lipase increased	1/42 (2.4%)	3
Lymphocyte count decreased	9/42 (21.4%)	9
Lymphopenia	3/42 (7.1%)	7
Neutrophil count decreased	6/42 (14.3%)	28
Platelet count decreased	6/42 (14.3%)	17
Serum cholesterol increased	1/42 (2.4%)	1
Weight loss	2/42 (4.8%)	2
Metabolism and nutrition disorders
Anorexia	14/42 (33.3%)	26
Blood bicarbonate decreased	1/42 (2.4%)	1
Blood glucose increased	10/42 (23.8%)	28
Dehydration	3/42 (7.1%)	7
Hyperglycemia	6/42 (14.3%)	10
Hyperkalemia	3/42 (7.1%)	6
Hypernatremia	1/42 (2.4%)	1
Hypoalbuminemia	1/42 (2.4%)	1
Hypocalcemia	2/42 (4.8%)	4
Hypoglycemia	2/42 (4.8%)	8
Hypomagnesemia	1/42 (2.4%)	3
Hyponatremia	2/42 (4.8%)	11
Serum albumin decreased	5/42 (11.9%)	10
Serum calcium decreased	6/42 (14.3%)	9
Serum glucose decreased	3/42 (7.1%)	3
Serum magnesium increased	1/42 (2.4%)	1
Serum phosphate decreased	2/42 (4.8%)	2
Serum potassium decreased	3/42 (7.1%)	5
Serum potassium increased	4/42 (9.5%)	7
Serum sodium decreased	7/42 (16.7%)	8
Serum sodium increased	1/42 (2.4%)	3
Serum triglycerides increased	1/42 (2.4%)	2
Musculoskeletal and connective tissue disorders
Back pain	4/42 (9.5%)	11
Bone pain	3/42 (7.1%)	7
Chest wall pain	4/42 (9.5%)	4
Joint pain	12/42 (28.6%)	30
Muscle weakness	3/42 (7.1%)	4
Musculoskeletal disorder	2/42 (4.8%)	3
Myalgia	10/42 (23.8%)	22
Neck pain	1/42 (2.4%)	2
Pain in extremity	8/42 (19%)	10
Nervous system disorders
Ataxia	1/42 (2.4%)	5
Dizziness	6/42 (14.3%)	18
Headache	11/42 (26.2%)	33
Memory impairment	2/42 (4.8%)	3
Neuralgia	1/42 (2.4%)	1
Neurological disorder NOS	2/42 (4.8%)	2
Peripheral motor neuropathy	2/42 (4.8%)	7
Peripheral sensory neuropathy	18/42 (42.9%)	66
Seizure	1/42 (2.4%)	1
Speech disorder	1/42 (2.4%)	3
Syncope	1/42 (2.4%)	1
Taste alteration	1/42 (2.4%)	1
Psychiatric disorders
Anxiety	3/42 (7.1%)	6
Confusion	1/42 (2.4%)	1
Depression	4/42 (9.5%)	6
Insomnia	5/42 (11.9%)	18
Renal and urinary disorders
Protein urine positive	1/42 (2.4%)	1
Urinary frequency	1/42 (2.4%)	1
Urinary incontinence	1/42 (2.4%)	1
Urinary retention	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	5/42 (11.9%)	16
Bronchospasm	3/42 (7.1%)	9
Cough	13/42 (31%)	42
Dyspnea	18/42 (42.9%)	51
Hemorrhage nasal	1/42 (2.4%)	6
Hypoxia	1/42 (2.4%)	1
Laryngeal obstruction	1/42 (2.4%)	1
Pharyngolaryngeal pain	1/42 (2.4%)	1
Pleuritic pain	1/42 (2.4%)	2
Pneumonitis	1/42 (2.4%)	5
Pulmonary hemorrhage	1/42 (2.4%)	1
Respiratory disorder	1/42 (2.4%)	4
Voice alteration	1/42 (2.4%)	3
Skin and subcutaneous tissue disorders
Alopecia	1/42 (2.4%)	2
Dry skin	3/42 (7.1%)	20
Pruritus	5/42 (11.9%)	27
Rash acneiform	2/42 (4.8%)	4
Rash desquamating	7/42 (16.7%)	15
Scalp pain	1/42 (2.4%)	4
Skin disorder	1/42 (2.4%)	1
Sweating	3/42 (7.1%)	15
Vascular disorders
Flushing	2/42 (4.8%)	2
Hematoma	1/42 (2.4%)	2
Hot flashes	1/42 (2.4%)	6
Hypertension	1/42 (2.4%)	1
Hypotension	3/42 (7.1%)	3

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.