RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Zoledronate may delay or prevent the formation of bone metastases. It is not yet known whether chemotherapy is more effective with or without zoledronate in treating non-small cell lung cancer and preventing bone metastases.

PURPOSE: This randomized phase II trial is studying docetaxel and carboplatin alone to see how well it works compared to giving docetaxel and carboplatin together with zoledronate in treating patients with unresectable stage IIIB or stage IV non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
Adenocarcinoma of the Lung large cell lung cancer Squamous Cell Lung Cancer stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer	Drug: carboplatin  Drug: docetaxel  Drug: zoledronate  Procedure: bone metastases prevention  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare the proportion of patients without disease progression at 6 months among patients with unresectable stage IIIB or stage IV non-small cell lung cancer treated with docetaxel and carboplatin with vs without zoledronate.

Secondary

• Compare time to disease progression in patients treated with these regimens.
• Compare response rate in patients treated with these regimens.
• Compare time to progression in bone in patients treated with these regimens.
• Compare 1-year overall survival in patients treated with these regimens.
• Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 1 hour followed by zoledronate IV over 15 minutes and carboplatin IV over 15 minutes on day 1.
• Arm II: Patients receive docetaxel IV over 1 hour followed by carboplatin IV over 15 minutes on day 1. In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses of therapy, patients in arm I who have responding or stable disease are then re-randomized to 1 of 2 arms.
• Arm I: Patients receive zoledronate IV over 15 minutes monthly for 12 months from the date of the first chemotherapy dose.
• Arm II: Patients receive no further treatment. Patients are followed every 1 or 3 months for 12 months from the date of the first chemotherapy dose.

PROJECTED ACCRUAL: Approximately 250 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed non-small cell lung cancer (NSCLC), including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma
• Unresectable stage IIIB disease, including patients with pleural effusion
• Patients with stage IIIB who are candidates for combined chemotherapy and chest irradiation are not eligible
• Stage IV disease
• No mixed tumors with small cell carcinoma or aplastic carcinoma
• Measurable disease
• At least one measurable lesion outside a previously irradiated area and detectable by radiologic studies
• No bone metastases
• No brain metastases unless treated and stable for at least 8 weeks

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 3 months

Hematopoietic

• WBC ≥ 1,500/mm^3
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• Bilirubin ≤ upper limit of normal (ULN)
• Alkaline phosphatase and AST/ALT must meet criteria for one of the following:
• AST or ALT ≤ 5 times ULN AND alkaline phosphatase ≤ ULN
• AST or ALT ≤1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN
• AST or ALT ≤ ULN AND alkaline phosphatase ≤ 5 times ULN
• No hepatic disease that would preclude prolonged follow-up

Renal

• Creatinine clearance > 60 mL/min
• Calcium ≥ 8.0 mg/dL (corrected)
• No renal disease that would preclude prolonged follow-up

Cardiovascular

• No cardiovascular disease that would preclude prolonged follow-up

Pulmonary

• No pulmonary disease that would preclude prolonged follow-up

Other

• No weight loss > 5% within the past 6 months
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except treated melanoma, ductal carcinoma in situ of the cervix, or other cancer cured by resection alone
• No known hypersensitivity to zoledronate, other bisphosphonates, platinum-containing compounds, mannitol, or polysorbate 80
• No peripheral neuropathy > grade 1
• No uncontrolled infections
• No uncontrolled type 2 diabetes mellitus
• No disease with influence on bone metabolism, including any of the following:
• Paget's disease
• Uncontrolled thyroid dysfunction
• Uncontrolled parathyroid dysfunction
• No neurologic/psychiatric disease that would preclude prolonged follow-up
• No other medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior first-line chemotherapy
• Prior adjuvant or neoadjuvant treatment (including paclitaxel) for NSCLC is allowed

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy covering > 30% of marrow-bearing areas
• No concurrent radiotherapy

Surgery

• More than 3 weeks since prior thoracotomy and recovered

Other

• More than 30 days since prior systemic investigational drugs or devices
• More than 1 year since prior bisphosphonates
• No other concurrent bisphosphonates
• No other concurrent osteoclastic bone resorption inhibitors (e.g., calcitonin, mithramycin, or gallium nitrate)
• No other concurrent investigational drugs or devices
• No other concurrent antineoplastic agents during the treatment phase of study

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-5907,  United States; Recruiting

Study chairs or principal investigators

Robert Alan Figlin, MD, FACP,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000389497; UCLA-0405098-01; NOVARTIS-CZO4L44EUS75; NCT00093717
Record last reviewed:  September 2004
Last Updated:  February 24, 2005
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093717
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08