Clinical trial NCT00970684: Bevacizumab, Docetaxel, and Gemcitabine Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-09-02
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival(PFS)
timeFrame: 1 year
Secondary outcomes:
measure: Median Time to Progression
timeFrame: 1 year
measure: Best Response
timeFrame: 1 year
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Fairview Hospital, Moll Pavilion
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital, a Cleveland Clinic Hospital
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Nathan Pennell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Afshin Dowlati, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patil PD, Shapiro M, Hashemi Sadraei N, Pennell NA. An Open-Label Phase II Trial of Bevacizumab plus Docetaxel and Gemcitabine in Advanced, Previously Untreated Nonsquamous Non-Small Cell Lung Cancer. Oncologist. 2019 Apr;24(4):457-e126. doi: 10.1634/theoncologist.2018-0857. Epub 2019 Jan 2.