Bevacizumab, Docetaxel, and Gemcitabine Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

• Sponsor: Nathan Pennell, MD, PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00970684
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 13
• Locations: 4
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 3.3
• 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. Drugs used in chemotherapy, such as docetaxel and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with docetaxel and gemcitabine hydrochloride may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with docetaxel and gemcitabine hydrochloride works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

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

Detailed Description

OBJECTIVES:

Primary

• Estimate the 1-year progression-free survival rate in patients with stage IIIB, stage IV, or recurrent non-squamous cell non-small cell lung cancer treated with bevacizumab, docetaxel, and gemcitabine hydrochloride.

Secondary

• Evaluate the median time to progression in patients treated with this regimen.

• Estimate the response rate in patients treated with this regimen.

• Determine the median overall survival of patients treated with this regimen.

• Determine the incidence of adverse events associated with this regimen in these patients.

OUTLINE: Patients receive bevacizumab IV over 30-90 minutes and docetaxel IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease may then continue to receive bevacizumab alone for up to 12 months in the absence of disease progression.

After completion of study treatment, patients are followed up every 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Bevacizumab Plus Docetaxel and Gemcitabine in Subjects With Advanced, Previously Untreated, Non-Squamous Non-Small Cell Lung Cancer
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bevacizumab, Docetaxel, and Gemcitabine Treatment repeats every 21 days for up to 6 courses.	Biological: bevacizumab; 15 mg/kg on day 1 of a 21-day cycle; Drug: docetaxel; 75 mg/m2 on day 1; Drug: gemcitabine hydrochloride; 900 mg/m2 on days 1, and 8,

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival(PFS) [1 year]

   PFS is defined as time to death or first occurrence of documented disease progression assessed by the investigator as per the RECIST guidelines (at lease a 20% increase in the diameter of a lesion, in addition to an absolute increase of 5mm). If no deaths occur prior to progression, this measure will be the same as the median time to progression.

Secondary Outcome Measures

1. Median Time to Progression [1 year]

   Time to progression (TTP) is defined as the time from start of treatment to first evidence of disease progression, defined per the RECIST 1.1 criteria as at least a 20% increase in the diameter of a lesion and an absolute increase of at least 5mm.

2. Best Response [1 year]

   The number of patients with a response will be assessed using the RECIST criteria of complete response (the disappearance of all target lesions); partial response (at least a 30% decrease in the diameter of lesions); progressive disease at least a 20% increase in the diameter of lesions); or stable disease(neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed non-squamous cell non-small cell lung cancer

• Stage IIIB (with pleural effusion), stage IV, or recurrent disease

• Bidimensionally measurable disease

• No known CNS disease, except for previously treated brain metastasis defined as no evidence of progression or hemorrhage after treatment AND no ongoing requirement for dexamethasone as documented by clinical examination, MRI, or CT scan

• Treatment for brain metastases may have included whole brain radiotherapy, radiosurgery (gamma knife, LINAC, or equivalent), or a combination of therapy as deemed appropriate by the treating physician

• Stable dose of anticonvulsants allowed

• No known metastatic disease to the gastrointestinal tract (e.g., stomach, small bowel, or large bowel)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Life expectancy > 3 months

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9 g/dL

• Bilirubin ≤ 2.0 mg/dL

• AST or ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if hepatic metastases are present)

• Serum creatinine ≤ 1.8 mg/dL

• Urine protein:creatinine ratio < 1.0 OR proteinuria < 2+ by urine dipstick OR ≤ 1 g of protein by 24-hour urine collection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Available for regular follow-ups

• No inadequately controlled hypertension, defined as systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg despite antihypertensive medications

• No history of hypertensive crisis or hypertensive encephalopathy

• No NYHA class II-IV congestive heart failure

• No myocardial infarction or unstable angina within the past 6 months

• No stroke or transient ischemic attack within the past 6 months

• No significant vascular disease (e.g., aortic aneurysm, aortic dissection requiring surgical repair, or recent peripheral arterial thrombosis) within the past 6 months

• No symptomatic peripheral vascular disease

• No evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)

• No history of colonic diverticular disease (i.e., diverticulosis or diverticulitis)

• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

• No serious, nonhealing wound, ulcer, or bone fracture

• No known hypersensitivity to any component of bevacizumab

• No hemoptysis (bright red blood of ≥ ½ teaspoon per episode) within the past 3 months

• No significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy or biological therapy

• No prior radiotherapy to an area of measurable disease unless there is documented progressive disease after completion of therapy

• More than 2 weeks since prior radiotherapy

• More than 4 weeks since prior and no concurrent participation in another experimental drug study, except for a Genentech-sponsored bevacizumab cancer study

• More than 28 days since prior major surgical procedure or open biopsy

• More than 3 months since prior abdominal surgery

• More than 3 months since prior neurosurgical resection or brain biopsy

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

• No concurrent major surgical procedure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
2	Fairview Hospital, Moll Pavilion	Cleveland	Ohio	United States	44111
3	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195
4	Hillcrest Hospital, a Cleveland Clinic Hospital	Mayfield Heights	Ohio	United States	44124

Sponsors and Collaborators

• Nathan Pennell, MD, PhD
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nathan Pennell, MD, PhD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
• Principal Investigator: Afshin Dowlati, MD, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nathan Pennell, MD, PhD, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00970684
• Other Study ID Numbers: CASE4507; P30CA043703; CASE4507; CASE 4507-CC694; NCI-2010-00547
• First Posted: Sep 2, 2009
• Last Update Posted: Aug 16, 2022
• Last Verified: Jul 1, 2022

• Keywords provided by Nathan Pennell, MD, PhD, Principal Investigator, Case Comprehensive Cancer Center: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine; Bevacizumab; Docetaxel

Study Results

Participant Flow

Recruitment Details	Patients were recruited from local medical clinics from 12/2009 to 4/2011

Arm/Group Title	Bevacizumab, Docetaxel, and Gemcitabine
Arm/Group Description	Treatment repeats every 21 days for up to 6 courses.
Period Title: Overall Study
STARTED	13
COMPLETED	3
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Bevacizumab, Docetaxel, and Gemcitabine
Arm/Group Description	Treatment repeats every 21 days for up to 6 courses.
Overall Participants	13
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	2 15.4%
Male	11 84.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%
Not Hispanic or Latino	12 92.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	13 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival(PFS)
Description	PFS is defined as time to death or first occurrence of documented disease progression assessed by the investigator as per the RECIST guidelines (at lease a 20% increase in the diameter of a lesion, in addition to an absolute increase of 5mm). If no deaths occur prior to progression, this measure will be the same as the median time to progression.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Intent to treat

Arm/Group Title	Bevacizumab, Docetaxel, and Gemcitabine
Arm/Group Description	Treatment repeats every 21 days for up to 6 courses.
Measure Participants	13
Median (95% Confidence Interval) [months]	5.6

2. Secondary Outcome

Title	Median Time to Progression
Description	Time to progression (TTP) is defined as the time from start of treatment to first evidence of disease progression, defined per the RECIST 1.1 criteria as at least a 20% increase in the diameter of a lesion and an absolute increase of at least 5mm.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Intent to treat

Arm/Group Title	Bevacizumab, Docetaxel, and Gemcitabine
Arm/Group Description	Treatment repeats every 21 days for up to 6 courses.
Measure Participants	13
Median (95% Confidence Interval) [months]	5.6

3. Secondary Outcome

Title	Best Response
Description	The number of patients with a response will be assessed using the RECIST criteria of complete response (the disappearance of all target lesions); partial response (at least a 30% decrease in the diameter of lesions); progressive disease at least a 20% increase in the diameter of lesions); or stable disease(neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

One patient was unevaluable for response due to missing baseline tumor measurement.

Arm/Group Title	Bevacizumab, Docetaxel, and Gemcitabine
Arm/Group Description	Treatment repeats every 21 days for up to 6 courses.
Measure Participants	12
Stable Disease	2 15.4%
Partial Response	9 69.2%
Progressive Disease	1 7.7%

Adverse Events

Time Frame	Patients are followed for adverse events while on study for up to 2 years.
Arm/Group Title	Bevacizumab, Docetaxel, and Gemcitabine
Arm/Group Description	Treatment repeats every 21 days for up to 6 courses.
All Cause Mortality
	Bevacizumab, Docetaxel, and Gemcitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bevacizumab, Docetaxel, and Gemcitabine
	Affected / at Risk (%)	# Events
Total	10/13 (76.9%)
Blood and lymphatic system disorders
Anemia	1/13 (7.7%)
Neutropenia	2/13 (15.4%)
Thrombocytopenia	1/13 (7.7%)
Cardiac disorders
Atrial fibrillation	2/13 (15.4%)
Nervous system disorders
Depressed Level of Consciousness	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Lung Infection	7/13 (53.8%)
Pleural Effusion	1/13 (7.7%)
Upper Respiratory Infection	1/13 (7.7%)
Pneumonitis	2/13 (15.4%)
Vascular disorders
Thromboembolic event	3/13 (23.1%)
Other (Not Including Serious) Adverse Events
	Bevacizumab, Docetaxel, and Gemcitabine
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Anemia	1/13 (7.7%)
Hemoglobinemia	10/13 (76.9%)
Leukocytopenia	12/13 (92.3%)
Lymphopenia	10/13 (76.9%)
Neutropenia	13/13 (100%)
Thrombocytopenia	8/13 (61.5%)
Hemorrhage/Bleeding	3/13 (23.1%)
Edema-limb	3/13 (23.1%)
Lymphocele	1/13 (7.7%)
Cardiac disorders
Superaventricular and nodal arrhythmia-Atrial fibrillation	2/13 (15.4%)
Supraventricular and nodal arrythmia-Sinus tachycardia	1/13 (7.7%)
Hypertension	2/13 (15.4%)
Hypotension	1/13 (7.7%)
Ear and labyrinth disorders
Tinnitus	2/13 (15.4%)
Endocrine disorders
Night Sweats, intermittent	1/13 (7.7%)
Eye disorders
Dry eye syndrome	1/13 (7.7%)
Epiphora	5/13 (38.5%)
Pain- eye	1/13 (7.7%)
Gastrointestinal disorders
Anorexia	10/13 (76.9%)
Colitis	1/13 (7.7%)
Constipation	8/13 (61.5%)
Dehydration	3/13 (23.1%)
Diarrhea	8/13 (61.5%)
Heartburn/dyspepsia	2/13 (15.4%)
Hemorrhoids	3/13 (23.1%)
Mucositis/stomatitis-oral	10/13 (76.9%)
Mucositis/stomatitis-rectum	1/13 (7.7%)
Nausea	9/13 (69.2%)
Dysgeusia	8/13 (61.5%)
Vomiting	6/13 (46.2%)
Hemorrhage, GI	4/13 (30.8%)
Pain- Abdomen NOS	1/13 (7.7%)
General disorders
Fatigue	10/13 (76.9%)
Fever	2/13 (15.4%)
Insomnia	5/13 (38.5%)
Rigors/chills	1/13 (7.7%)
Sweating	3/13 (23.1%)
Weight gain	1/13 (7.7%)
Weight loss	6/13 (46.2%)
Pain- dental/teeth/peridontal	1/13 (7.7%)
Pain-other	4/13 (30.8%)
Pain- Throat/pharynx/larynx	1/13 (7.7%)
Immune system disorders
Allergic reaction/hypersensitivity	5/13 (38.5%)
Infections and infestations
Infection-Lung	4/13 (30.8%)
Infection	6/13 (46.2%)
Infection-Bladder	1/13 (7.7%)
Infection-Conjuctiva	1/13 (7.7%)
Infection-Mucosa	2/13 (15.4%)
Infection-Upper aerodigestive NOS	1/13 (7.7%)
Opportunistic infection	1/13 (7.7%)
Metabolism and nutrition disorders
ALT, SGPT	4/13 (30.8%)
AST, SGOT	5/13 (38.5%)
Hypoalbuminemia	4/13 (30.8%)
Alkaline phosphatase	3/13 (23.1%)
Hypocalcemia	3/13 (23.1%)
Hyperglycemia	12/13 (92.3%)
Hypoglycemia	1/13 (7.7%)
Hypomagnesemia	1/13 (7.7%)
Glycosuria	1/13 (7.7%)
Hypophosphatemia	1/13 (7.7%)
Hyperkalemia	5/13 (38.5%)
Proteinuria	7/13 (53.8%)
Hyponatremia	7/13 (53.8%)
Musculoskeletal and connective tissue disorders
Arthritis	1/13 (7.7%)
Fracture	1/13 (7.7%)
Pain- Muscular/skeletal	9/13 (69.2%)
Nervous system disorders
Confusion	2/13 (15.4%)
Dizziness	4/13 (30.8%)
Extrapyramidal/involuntary movement/restlessness	2/13 (15.4%)
Mood alterations	6/13 (46.2%)
Neuropathy	8/13 (61.5%)
Somnolence	1/13 (7.7%)
Pain- Head/headache	6/13 (46.2%)
Reproductive system and breast disorders
Sexual/reproductive function	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Hemorrhage-pulmonary/upper respiratory	7/13 (53.8%)
Pain- Chest/thorax	3/13 (23.1%)
Cough	5/13 (38.5%)
Dyspnea	6/13 (46.2%)
Hypoxia	4/13 (30.8%)
Pleural effusion	1/13 (7.7%)
Pneumonititis/pulmonary infiltrates	2/13 (15.4%)
Bronchospasm, wheezing	1/13 (7.7%)
Voice changes/dysarthria	3/13 (23.1%)
Hiccups	2/13 (15.4%)
Skin and subcutaneous tissue disorders
Bruising	1/13 (7.7%)
Dry skin	6/13 (46.2%)
Flushing	1/13 (7.7%)
Alopecia	7/13 (53.8%)
Nail changes	4/13 (30.8%)
Rash- acne/acneiform	5/13 (38.5%)
Ulceration	2/13 (15.4%)
Vascular disorders
Thrombosis	2/13 (15.4%)

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.