Non Small Cell Lung Cancer
Conditions
Keywords
ZD6474, VANDETANIB, ZACTIMA, ADVANCED, NSCLC, LUNG CANCER, ELDERLY PATIENTS, GEMCITABINE, PHASE II, RANDOMIZED, DOUBLE-BLIND, histologically or cytologically-confirmed advanced (stage IIIB with supraclavicular lymph node metastases or pleural effusion or stage IV) NSCLC
Brief summary
The primary objective of this study is to demonstrate an improvement in Progression-Free Survival (PFS) for the combination of vandetanib plus gemcitabine compared with gemcitabine plus placebo in chemonaïve (not including an adjuvant regimen) patients aged ≥ 70 years with advanced NSCLC.
Interventions
100 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
DRUGPlacebo to Match ZD6474, Vandetanib
100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
DRUGGemcitabine
administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle UP to 6 cycles or UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic confirmation of advanced NSCLC (stage IIIB with supraclavicular lymph node metastases or pleural effusion or stage IV) on entry into study * One or more measurable lesions at least 10 mm in the longest diameter (LD) by spiral CT scan or 20 mm with conventional techniques according to RECIST criteria * Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted). * Female or male aged 70 years or above
Exclusion criteria
* Patients must not have received prior anti-cancer therapy except in the adjuvant setting * Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial * Significant cardiovascular event (e.g. myocardial infarction, superior vena cava \[SVC\] syndrome, New York Heart Association \[NYHA\] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of * History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival | Oct 2008- dec 2011 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Oct 2008- dec 2011 | — |
| Overall Objective Response | Oct 2008- dec 2011 | — |
| Duration of Response | Oct 2008- dec 2011 | — |
| The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine | Oct 2008- Dec 2011 | The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine is defined as the number of Adverse Events which includes any symptoms and/or Clinically Significant Laboratory or Vital Signs Abnormalities, and/or ECGs Changes |
Countries
Italy
Participant flow
Recruitment details
A total of 124 patients have been enrolled in a period of 19 months in 17 actively recruiting Oncologic Medical Department in Italy.
Participants by arm
| Arm | Count |
|---|---|
| ZD6474 (Vandetanib),Gemcitabine Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued. | 61 |
| Placebo to Match ZD6474 (Vandetanib),Gemcitabine Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1. . Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued. | 63 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 26 | 18 |
| Overall Study | Death | 3 | 3 |
| Overall Study | Lack of Efficacy | 21 | 34 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 7 | 5 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | ZD6474 (Vandetanib),Gemcitabine | Total | Placebo to Match ZD6474 (Vandetanib),Gemcitabine |
|---|---|---|---|
| Age, Continuous | 75.03 years STANDARD_DEVIATION 3.34 | 75.25 years STANDARD_DEVIATION 3.41 | 75.48 years STANDARD_DEVIATION 3.49 |
| Sex: Female, Male Female | 16 Participants | 34 Participants | 18 Participants |
| Sex: Female, Male Male | 45 Participants | 90 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 59 / 61 | 62 / 63 |
| serious Total, serious adverse events | 26 / 61 | 25 / 63 |
Outcome results
Primary
Progression Free Survival
Time frame: Oct 2008- dec 2011
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ZD6474 (Vandetanib),Gemcitabine | Progression Free Survival | 183 days |
| Placebo to Match ZD6474 (Vandetanib),Gemcitabine | Progression Free Survival | 169 days |
Secondary
Duration of Response
Time frame: Oct 2008- dec 2011
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ZD6474 (Vandetanib),Gemcitabine | Duration of Response | 225 days |
| Placebo to Match ZD6474 (Vandetanib),Gemcitabine | Duration of Response | 214 days |
Secondary
Overall Objective Response
Time frame: Oct 2008- dec 2011
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD6474 (Vandetanib),Gemcitabine | Overall Objective Response | 9 Participants |
| Placebo to Match ZD6474 (Vandetanib),Gemcitabine | Overall Objective Response | 8 Participants |
Secondary
Overall Survival
Time frame: Oct 2008- dec 2011
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ZD6474 (Vandetanib),Gemcitabine | Overall Survival | 262 days |
| Placebo to Match ZD6474 (Vandetanib),Gemcitabine | Overall Survival | 305 days |
Secondary
The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine
The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine is defined as the number of Adverse Events which includes any symptoms and/or Clinically Significant Laboratory or Vital Signs Abnormalities, and/or ECGs Changes
Time frame: Oct 2008- Dec 2011
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD6474 (Vandetanib),Gemcitabine | The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine | 378 Adverse Events |
| Placebo to Match ZD6474 (Vandetanib),Gemcitabine | The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine | 381 Adverse Events |