Bevacizumab and Docetaxel in Treating Older Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00541099
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 11
• Locations: 3
• Arm: 1
• Duration (Months): 60
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, also work in different ways to kill tumor cells or stop them from growing. Giving bevacizumab together with docetaxel may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with docetaxel works in treating older patients with stage III or stage IV non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: bevacizumab; Drug: docetaxel	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the proportion of elderly (≥ 75 years of age) patients with stage III or IV non-small cell lung cancer surviving for at least 6 months when treated with a combination of bevacizumab and weekly docetaxel.

Secondary

• To assess the progression-free and overall survival of patients treated with this regimen.

• To determine the response rate in patients treated with this regimen.

• To assess the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and docetaxel IV on days 1, 8, and 15. Treatment may repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Bevacizumab and Weekly Docetaxel in Elderly (≥ 75 Years) Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avastin & Docetaxel Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15	Biological: bevacizumab; Avastin 10.0 mg/kg on days 1 and 15; Other Names: Avastin ; Drug: docetaxel; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15; Other Names: TAXOTERE®

Outcome Measures

Primary Outcome Measures

1. Survival [6 months when treated with combination of Avastin and weekly docetaxel]

Secondary Outcome Measures

1. Progression-free Survival [6 months when treated with combination of Avastin and weekly docetaxel]

   Progression-free survival in months via the Kaplan-Meier method

2. Overall Survival [4 weeks after removal from study or until death]

   Overall survival using Kaplan-Meier method.

3. Response Rate [Every 8 weeks]

4. Toxicity According to NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [1st and 2nd week of each 21 day cycle, up to six cycles.]

   Toxicity: using the highest grade of each toxicity experienced by each patient according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 75 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically or cytologically confirmed non-small cell lung cancer

• Stage III or IV disease

• Stage III disease allowed, provided the patient is not a candidate for concurrent chemotherapy and radiotherapy

• Mixed histology allowed, provided the biopsy has less than 50% squamous cell histology

• Measurable or evaluable disease

Exclusion criteria:

• Squamous cell histology

• Evidence of cavitation in the tumor

• Tumors in close proximity to major blood vessels

• No active, untreated brain metastases

• More than 7 days since prior treatment for brain metastases AND no evidence of hemorrhage in the lesion

• Stable or declining dose of steroids allowed

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

• Life expectancy > 12 weeks

• Leukocytes ≥ 3,000/μL

• Absolute neutrophil count ≥ 1,500/μL

• Platelet count ≥ 100,000/μL

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT ≤ 2.5 times ULN (< 5 times ULN if patients has liver metastases)

• Creatinine ≤ 1.5 times normal

• Left ventricular function ≥ normal by MUGA scan or ECHO

• Urine protein:creatinine ratio ≤ 1.0 AND/OR urine protein ≤ 1+ by dipstick analysis OR protein ≤ 1 g/24-hour urine collection

• Fertile patients must use effective contraception and women should avoid breastfeeding

Exclusion criteria:

• Resting blood pressure (BP) consistently > 140/90 mm Hg

• Patients whose BP is controlled (≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic) after adjusting, starting, or increasing the medications are eligible

• Significant hemorrhage (i.e., > 30 mL bleeding/episode ) or hemoptysis (i.e., > 5 mL fresh blood in one episode) in the previous 3 months

• Evidence of bleeding diathesis or coagulopathy

• Significant traumatic injury within the past 28 days

• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

• History of other active malignancies

• If patient has other cancers such as PSA only (without clinical or radiographic evidence) prostate cancer, the patient can still be considered for this protocol if, in the clinical judgment of the treating physician, NSCLC is the most important malignancy and the other malignancy will not impact patient's overall survival

• Myocardial infarction or cerebrovascular episode within the past year

• Serious nonhealing wound or ulcer

• Significant vascular disease such as aortic aneurysm, aortic dissection, or symptomatic peripheral vascular disease

• Uncontrolled concurrent illness that would limit compliance with study requirements including, but not limited to, the following:

• Ongoing or active infection

• New York Heart Association class II-IV congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness/social situations

• Known hypersensitivity to any component of bevacizumab

PRIOR CONCURRENT THERAPY:

• More than 7 days since prior radiotherapy and recovered

• No concurrent full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular-weight heparin)

• More than 10 days since prior and no concurrent aspirin ≥ 325 mg/day or chronic use of nonsteroidal anti-inflammatory drugs

• More than 28 days since prior and no concurrent major surgical procedure or open biopsy

• More than 7 days since prior core biopsy or other minor procedure, excluding placement of a vascular access device

• No other concurrent investigational agents, commercial agents, or therapies

• More than 30 days since prior participation in a trial involving an investigational agent

• No prior chemotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
2	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
3	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Shirish M. Gadgeel, MD, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

None provided.

• Responsible Party: Shirish M. Gadgeel, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00541099
• Other Study ID Numbers: CDR0000555019; P30CA022453; WSU-2007-053; NCT01665443
• First Posted: Oct 8, 2007
• Last Update Posted: Mar 27, 2019
• Last Verified: Aug 1, 2014

• Keywords provided by Shirish M. Gadgeel, Principal Investigator, Barbara Ann Karmanos Cancer Institute: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Bevacizumab; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
Period Title: Overall Study
STARTED	11
COMPLETED	8
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	79.7 (4.15)
Sex: Female, Male (Count of Participants)
Female	3 37.5%
Male	5 62.5%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Survival
Time Frame	6 months when treated with combination of Avastin and weekly docetaxel

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
Measure Participants	8
Number (90% Confidence Interval) [percentage of participants surviving]	75 937.5%

2. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival in months via the Kaplan-Meier method
Time Frame	6 months when treated with combination of Avastin and weekly docetaxel

Outcome Measure Data

Analysis Population Description

No patient showed a response, therefore all patients had 0 for PFS

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
Measure Participants	0

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival using Kaplan-Meier method.
Time Frame	4 weeks after removal from study or until death

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
Measure Participants	8
Median (95% Confidence Interval) [months]	35.7

4. Secondary Outcome

Title	Response Rate
Time Frame	Every 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
Measure Participants	8
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Toxicity According to NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Description	Toxicity: using the highest grade of each toxicity experienced by each patient according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time Frame	1st and 2nd week of each 21 day cycle, up to six cycles.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
Measure Participants	8
Serious (grade 3 or 4)	21
other (grade 0, 1, or 2)	123

Adverse Events

Arm/Group Title	Avastin & Docetaxel
Arm/Group Description	Avastin 10.0 mg/kg on days 1 and 15; Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel; Docetaxel 35 mg/m2 on day 1, 8, 15 bevacizumab: Avastin 10.0 mg/kg on days 1 and 15 docetaxel: Dexamethasone 4 mg evening before, morning of and evening of each dose of docetaxel.Docetaxel 35 mg/m2 on day 1, 8, 15
All Cause Mortality
	Avastin & Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Avastin & Docetaxel
	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)
Blood and lymphatic system disorders
Decreased ANC	1/8 (12.5%)	1
Decreased WBC	1/8 (12.5%)	1
Lymphopenia	2/8 (25%)	5
Cardiac disorders
Hypertension	1/8 (12.5%)	1
Gastrointestinal disorders
Diarrhea	3/8 (37.5%)	4
Perineal abscess	1/8 (12.5%)	1
General disorders
Fatigue	2/8 (25%)	2
Metabolism and nutrition disorders
Hyperglycemia	3/8 (37.5%)	8
Proteinuria	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness	1/8 (12.5%)	1
Nervous system disorders
Syncope	1/8 (12.5%)	1
Renal and urinary disorders
Urosepsis	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	2/8 (25%)	2
Pleural Effusion	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Avastin & Docetaxel
	Affected / at Risk (%)	# Events
Total	6/8 (75%)
Blood and lymphatic system disorders
Leukocytes	1/8 (12.5%)	1
Neutropenia	1/8 (12.5%)	1
Thrombocytopenia	1/8 (12.5%)	1
Leukpenia	1/8 (12.5%)	2
Cardiac disorders
Pericardial Effusion	1/8 (12.5%)	1
Eye disorders
Eye Tearing	1/8 (12.5%)	1
Lacrimation	1/8 (12.5%)	1
Tearing in eyes	1/8 (12.5%)	2
Watery Eye	1/8 (12.5%)	1
Gastrointestinal disorders
Acute Colitis	1/8 (12.5%)	1
Diarrhea	6/8 (75%)	19
Metallic taste	1/8 (12.5%)	1
Mucositis	1/8 (12.5%)	1
Nausea	2/8 (25%)	3
Oral Thrush	1/8 (12.5%)	1
Taste Alteration	4/8 (50%)	6
Vomiting	1/8 (12.5%)	3
Edema: limbs	1/8 (12.5%)	1
Edema: trunk/genital	1/8 (12.5%)	1
General disorders
Chills	1/8 (12.5%)	1
Fatigue	6/8 (75%)	16
Pain: Chest/Torax NOS	1/8 (12.5%)	2
R. Arm Extravasation	1/8 (12.5%)	1
Arm Laceration	1/8 (12.5%)	1
Decubitus	1/8 (12.5%)	2
Immune system disorders
Allergic Reaction	1/8 (12.5%)	2
Infections and infestations
UTI	3/8 (37.5%)	3
Urinary Tract Infection	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Bruising	1/8 (12.5%)	1
Fracture	1/8 (12.5%)	2
pain: Trauma site	1/8 (12.5%)	1
R. Elbow-Soft Tissue Trauma	1/8 (12.5%)	3
Investigations
Alkaline Phosphatase	1/8 (12.5%)	1
Decreased HgB	2/8 (25%)	7
Decreased WBC	3/8 (37.5%)	6
Hemoglobin	1/8 (12.5%)	5
Increased Creatinine	1/8 (12.5%)	2
Lymphopenia	1/8 (12.5%)	6
Weight Loss	2/8 (25%)	5
Metabolism and nutrition disorders
Anorexia	4/8 (50%)	6
Dehydration	3/8 (37.5%)	3
Hypercalcemia	1/8 (12.5%)	1
Hyperglycemia	2/8 (25%)	8
Hyperkalemia	1/8 (12.5%)	3
Hypoalbuminemia	5/8 (62.5%)	15
Hyponatremia	1/8 (12.5%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/8 (12.5%)	1
Bilateral Leg Pain	1/8 (12.5%)	1
Generalized muscle weakness	1/8 (12.5%)	5
Lower Back Pain	1/8 (12.5%)	1
Nervous system disorders
Dizziness	1/8 (12.5%)	1
Sensory Neuropathy	2/8 (25%)	2
Vasovagal episode	1/8 (12.5%)	2
Psychiatric disorders
Insomina	1/8 (12.5%)	1
Renal and urinary disorders
Proteinuria	3/8 (37.5%)	7
Urinary Frequency	1/8 (12.5%)	2
Reproductive system and breast disorders
Sinus Congest	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/8 (37.5%)	3
Dyspnea	1/8 (12.5%)	3
epistaxis	2/8 (25%)	2
Hypoxia	1/8 (12.5%)	1
Nose Bleed	3/8 (37.5%)	3
Pleural effusion	2/8 (25%)	3
Sinus Drainage	1/8 (12.5%)	1
Sore Throat	1/8 (12.5%)	1
upper resp infection	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Brittle Nails	1/8 (12.5%)	2
Alopecia	4/8 (50%)	5
Chest Wall Rash	1/8 (12.5%)	1
Dry Skin	1/8 (12.5%)	2
Hyperpigmentation	1/8 (12.5%)	2
Nail Changes	2/8 (25%)	2
Pruritis	1/8 (12.5%)	2
Skin peeling-hands	1/8 (12.5%)	1
Vascular disorders
Flushing	1/8 (12.5%)	1
HTN	1/8 (12.5%)	1
Hypotension	1/8 (12.5%)	1
Hypertension	3/8 (37.5%)	3

Limitations/Caveats

The increased use of pemetrexed in the front line setting affected accrual.

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.