A prospective, multicenter, randomized phase III study to evaluate the efficacy of Zometa (zoledronic acid) in preventing or delaying of bone metastasis in patients with stage III non-small cell lung cancer

• Register: EUCTR
• Last refreshed on: 16 February 2015
• Main ID: EUCTR2004-001101-10-ES
• Date of registration: 01/12/2005
• Prospective Registration: No
• Primary sponsor: Novartis Farmacéutica, S.A
• Public title: A prospective, multicenter, randomized phase III study to evaluate the efficacy of Zometa (zoledronic acid) in preventing or delaying of bone metastasis in patients with stage III non-small cell lung cancer
• Scientific title: A prospective, multicenter, randomized phase III study to evaluate the efficacy of Zometa (zoledronic acid) in preventing or delaying of bone metastasis in patients with stage III non-small cell lung cancer
• Date of first enrolment: 11/02/2005
• Target sample size: 446
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001101-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Belgium, Hungary, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Age = 18 years
• Histologically confirmed NSCLC (squamous cell carcinoma, adenocarcinoma, large cell
carcinoma) NOTE: Mixed tumors with small cell carcinoma and aplastic carcinoma are not eligible
• Newly diagnosed, Stage IIIA and Stage IIIB excluding patients with pleural effusion
• Life expectancy of at least 6 months
• ECOG performance status of 0 or 1 (Post-text suppl. 1)
• Weight loss = 5% in past 6 months
• Women of childbearing potential must use a medically acceptable form of contraception
during the study and must have a negative urine or serum pregnancy test within 7 days of
randomization.
• Adequate bone marrow reserve defined as white blood cell (WBC) = 3500mm3,
neutrophils = 1500 mm3, platelets = 100,000 mm3, Hb = 9 g/dL
• Able and willing to sign informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Patients with NSCLC with pleural effusion.
• Patients who received any prior bisphosphonates in past 12 months
• Presence of metastasis
• Patients with current malignancy within past 5 years other than NSCLC (exceptions
include treated melanoma, ductal carcinoma in situ of the cervix or other cancer cured by reception alone)
• Patients who have received radiotherapy = 3 weeks before randomization must have recovered from any adverse events occurring during radiotherapy
• Previous thoracotomy must have been performed = 3 weeks prior to randomization and patient must have recovered.
• Any previous radiotherapy completed < 3 weeks before randomization
• Patients with abnormal renal function (Creatinine > 3mg/dL)
• Corrected serum calcium < 8.0 mg/dL
• Known hypersensitivity to Zometa or other bisphosphonates
• Patients with nonmalignant conditions which would confound the evaluation of the
primary endpoint, impair tolerance of therapy, or prevent compliance to the protocol,
including:
- Uncontrolled infections
- Uncontrolled Type 2 Diabetes Mellitus
- Diseases with influence on bone metabolism such as Paget’s disease or uncontrolled thyroid or parathyroid dysfunction
- Cardiovascular, renal, hepatic, pulmonary and neurologic/psychiatric diseases which
would prevent prolonged follow-up
• Patients who, in the opinion of the investigator, are unlikely to cooperate fully during the study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with unresectable stage IIIA and IIIB Non small cell lung cancer (NSCLC) without bone metastases

Intervention(s)

Trade Name: Zometa 4mg
Product Name: Zometa 4mg/5ml concentrate for solution for infusion
Product Code: ZOL446
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Zoledronic acid
CAS Number: 118072-93-8
Current Sponsor code: ZOL446
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal

Primary Outcome(s)

Main Objective: The primary objective of the study is to evaluate the efficacy of Zometa in the prevention of bone metastases in patients with locally advanced, stage IIIA and IIIB NSCLC. The primary endpoint is time to occurrence of bone metastases. All patients in both arms will receive standard antineoplastic treatment at the discretion of their physicians. Patients in the treatment arm will receive Zometa every 3-4 weeks, depending on their chemotherapy regimen. For patients who are not receiving chemotherapy, the investigator decides whether Zometa will be given every 3 or every 4 weeks. The control arm will not receive Zometa treatment until development of bone metastases.

Secondary Objective: Secondary objectives include evaluation of:
• Rate of bone metastases (irrespective whether symptomatic or not ) at 6, 12, 18 and 24 months
• Time to disease progression (TTP)
• Risk of skeletal related events (SREs) at 12 and 24 months from study entry based on multiple event analysis by the Anderson-Gill method and rate of SRE at 12 and 24 months (proportion of patients having experienced at least one SRE) Skeletal-related events (SREs) are defined as:
- radiation therapy to bone (including the use of radioisotopes)
- surgery to bone
- spinal cord compression events
- pathologic bone fracture events
• Time to first SRE
• Survival at 12 and 24 months

Primary end point(s): The primary objective of the study is to evaluate the efficacy of Zometa in the prevention of bone metastases in patients with locally advanced, stage IIIA and IIIB NSCLC. The primary endpoint is time to occurrence of bone metastases. All patients in both arms will receive standard antineoplastic treatment at the discretion of their physicians. Patients in the treatment arm will receive Zometa every 3-4 weeks, depending on their chemotherapy regimen. For patients who are not receiving chemotherapy, the investigator decides whether Zometa will be given every 3 or every 4 weeks. The control arm will not receive Zometa treatment until development of bone metastases.

Secondary ID(s)

2004-001101-10-HU

CZOL446G2419