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

A Phase II Study of Bevacizumab Plus Docetaxel and Gemcitabine in Subjects With Advanced, Previously Untreated, Non-Squamous Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: bevacizumab; Drug: docetaxel; Drug: gemcitabine hydrochloride

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44111
      • Fairview Hospital, Moll Pavilion
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital, a Cleveland Clinic Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival(PFS)	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Progression	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.	1 year
Best Response	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)	1 year

Collaborators and Investigators

• Sponsor: Nathan Pennell, MD, PhD
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nathan Pennell, MD, PhD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: September 1, 2009
• First Submitted That Met QC Criteria: September 1, 2009
• First Posted (Estimate): September 2, 2009

Study Record Updates

• Last Update Posted (Actual): August 16, 2022
• Last Update Submitted That Met QC Criteria: July 22, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Docetaxel; Bevacizumab
• Other Study ID Numbers: CASE4507 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); CASE 4507-CC694 (Other Identifier: Cancer Center IRB); NCI-2010-00547 (Other Identifier: NCI/CTRP)