Mesothelioma
Conditions
Keywords
mesothelioma, zoledronic acid, zometa, bisphosphonate therapy, CT scan, PET scan
Brief summary
The primary objective of this trial is to determine the response rate of single agent zoledronic acid using a composite of criteria including the EORTC modified RECIST criteria and the EORTC tumor response criteria for 18F-FDG PET scans.
Detailed description
This pilot study will examine the effect of bisphosphonate (zoledronic acid) in patients with malignant mesothelioma. Evaluation will be limited to patients with standard (CT scans) and functional instruments (FDG PET Scans) of tumor assessment after the administration of standard doses of zoledronic acid (4 mg IV every 3 weeks). We will also explore the biologic effect of zoledronic acid in patients using new serum markers as well as several blood level markers.
Interventions
DRUGZometa
Zoledronic acid will be administered IV on the first day of a 21 day cycle at a concentration of 4 mg. The treatment will take about 30-60 minutes with the infusion lasting about 15 minutes.
Sponsors
Novartis Pharmaceuticals
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females \> 18 years of age * Life expectancy of at least 2 months * Histologically confirmed unresectable malignant pleural mesothelioma (MPM) * Measurable disease by CT Scan criteria and/or positive metabolic activity of 18F-FDG PET Scan criteria at screening * ECOG Performance Status of 0-2 * Laboratory and clinical results within 2 weeks prior to Day 1 must be as follows: 1. ANC ≥ 1.5 x 109/L 2. Platelet Count ≥ 100 x 109/L 3. Hemoglobin ≥ 9g/dL 4. Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) 5. AST ≤ 2.5 x ULN 6. ALT ≤ 2.5 x ULN 7. ALK-P ≤ 3 x ULN 8. Serum creatinine ≤ 1.8mg/dL 9. Calculated Serum Creatinine Clearance 40 - \> 60ml/min * Female subjects of childbearing potential and all male subjects must be surgically sterile or consent to use a medically acceptable method of contraception throughout the trial. * Willing and able to provide written informed consent.
Exclusion criteria
* Known central nervous system (CNS) tumor involvement * Evidence of other active malignancy requiring treatment * Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months) * Known infection with HIV or hepatitis * Clinically significant arrhythmias demonstrated on electrocardiogram (ECG). Note: subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia (SVT) are eligible. * Active, serious systemic disease, including active bacterial or fungal infection. * Subjects undergoing invasive dental procedures, significant periodontal disease or history of osteonecrosis of the jaw. * Treatment within 4 weeks of the start of the trial with other systemic anticancer therapy. * Breastfeeding, pregnant, or likely to become pregnant during the clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate Following Zoledronic Acid (Zometa) | Baseline up to 28 months or until progressive disease or death | The modified Response Evaluation Criteria in Solid Tumors Criteria (RECIST 2004) will be used for target lesions and assessed by CT scans. Complete Response (CR) is the disappearance of target lesions; Partial Response (PR) is greater than or equal to 30% reduction in the total tumor measurement; Stable Disease (SD) is the absence of response or progression; and Progressive Disease (PD) is a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline up to 28 months | Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced evidence of disease progression, as determined by radiological or clinical progression. |
| Overall Survival (OS) | Baseline up to 28 months | Overall Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced death or lost to follow-up. |
Countries
United States
Participant flow
Recruitment details
Inclusion criteria included: adult patients (age\>18) with unresectable Malignant Pleural Mesothelioma (MPM) who had progressed after one or more prior systemic therapies, had not received prior systemic therapy due to poor performance status (PS), and/or were unwilling to receive systemic chemotherapy.
Pre-assignment details
The primary objective of this study was to evaluate the anti-tumor activity of zoledronic acid (Zometa) in subjects with unresectable, advanced Malignant Pleural Mesothelioma (MPM).
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid (Zometa) Zometa (zoledronic acid) 4mg will be administered by infusion on Day 1 of a 3-week cycle followed by tumor assessment from CT and/or PET scans every 2 cycles. This will continue until progression of disease and/or intolerable toxicity. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Zoledronic Acid (Zometa) |
|---|---|
| Age, Continuous | 62 years |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Tumor Response Rate Following Zoledronic Acid (Zometa)
The modified Response Evaluation Criteria in Solid Tumors Criteria (RECIST 2004) will be used for target lesions and assessed by CT scans. Complete Response (CR) is the disappearance of target lesions; Partial Response (PR) is greater than or equal to 30% reduction in the total tumor measurement; Stable Disease (SD) is the absence of response or progression; and Progressive Disease (PD) is a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions.
Time frame: Baseline up to 28 months or until progressive disease or death
Population: Participants with advanced malignant pleural mesothelioma.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zometa | Tumor Response Rate Following Zoledronic Acid (Zometa) | 12.5 percentage of responders |
Secondary
Overall Survival (OS)
Overall Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced death or lost to follow-up.
Time frame: Baseline up to 28 months
Population: Participants with advanced malignant pleural mesothelioma.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zometa | Overall Survival (OS) | 7 months |
Secondary
Progression Free Survival (PFS)
Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced evidence of disease progression, as determined by radiological or clinical progression.
Time frame: Baseline up to 28 months
Population: Participants with advanced malignant pleural mesothelioma.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zometa | Progression Free Survival (PFS) | 2 Months |