Trial Outcomes & Findings for Zactima in Non Small Cell Lung Cancer (NSCLC) ELderly Patients In Combination With or Versus Gemcitabine (NCT NCT00753714)
NCT ID: NCT00753714
Last Updated: 2016-10-17
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
124 participants
Primary outcome timeframe
Oct 2008- dec 2011
Results posted on
2016-10-17
Participant Flow
A total of 124 patients have been enrolled in a period of 19 months in 17 actively recruiting Oncologic Medical Department in Italy.
Participant milestones
| Measure |
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.
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
61
|
63
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
60
|
62
|
Reasons for withdrawal
| Measure |
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.
|
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
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
21
|
34
|
|
Overall Study
Adverse Event
|
26
|
18
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Death
|
3
|
3
|
|
Overall Study
Other
|
7
|
5
|
Baseline Characteristics
Zactima in Non Small Cell Lung Cancer (NSCLC) ELderly Patients In Combination With or Versus Gemcitabine
Baseline characteristics by cohort
| Measure |
ZD6474 (Vandetanib),Gemcitabine
n=61 Participants
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.
|
Placebo to Match ZD6474 (Vandetanib),Gemcitabine
n=63 Participants
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.
|
Total
n=124 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
75.03 years
STANDARD_DEVIATION 3.34 • n=5 Participants
|
75.48 years
STANDARD_DEVIATION 3.49 • n=7 Participants
|
75.25 years
STANDARD_DEVIATION 3.41 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Oct 2008- dec 2011Outcome measures
| Measure |
ZD6474 (Vandetanib),Gemcitabine
n=61 Participants
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.
|
Placebo to Match ZD6474 (Vandetanib),Gemcitabine
n=63 Participants
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
|
|---|---|---|
|
Progression Free Survival
|
183 days
Interval 116.0 to 214.0
|
169 days
Interval 95.0 to 194.0
|
SECONDARY outcome
Timeframe: Oct 2008- dec 2011Outcome measures
| Measure |
ZD6474 (Vandetanib),Gemcitabine
n=61 Participants
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.
|
Placebo to Match ZD6474 (Vandetanib),Gemcitabine
n=63 Participants
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
|
|---|---|---|
|
Overall Survival
|
262 days
Interval 170.0 to 356.0
|
305 days
Interval 214.0 to 355.0
|
SECONDARY outcome
Timeframe: Oct 2008- dec 2011Outcome measures
| Measure |
ZD6474 (Vandetanib),Gemcitabine
n=61 Participants
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.
|
Placebo to Match ZD6474 (Vandetanib),Gemcitabine
n=63 Participants
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
|
|---|---|---|
|
Overall Objective Response
|
9 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Oct 2008- dec 2011Outcome measures
| Measure |
ZD6474 (Vandetanib),Gemcitabine
n=61 Participants
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.
|
Placebo to Match ZD6474 (Vandetanib),Gemcitabine
n=63 Participants
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
|
|---|---|---|
|
Duration of Response
|
225 days
Interval 175.0 to
Too few participants experienced event to compute upper limit of CI, i.e.sample analyzed is to small compared with the initial statistical plan or when less than 50% of the subjects are available for analysis
|
214 days
Interval 124.0 to 232.0
|
SECONDARY outcome
Timeframe: Oct 2008- Dec 2011The 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
Outcome measures
| Measure |
ZD6474 (Vandetanib),Gemcitabine
n=61 Participants
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.
|
Placebo to Match ZD6474 (Vandetanib),Gemcitabine
n=63 Participants
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
|
|---|---|---|
|
The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine
|
378 Adverse Events
|
381 Adverse Events
|
Adverse Events
ZD6474 (Gemcitabine), Vandetanib
Serious events: 26 serious events
Other events: 59 other events
Deaths: 0 deaths
Placebo to Match ZD6474 (Gemcitabine), Vandetanib
Serious events: 25 serious events
Other events: 62 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ZD6474 (Gemcitabine), Vandetanib
n=61 participants at risk
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.
|
Placebo to Match ZD6474 (Gemcitabine), Vandetanib
n=63 participants at risk
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
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.9%
3/61
|
14.3%
9/63
|
|
Respiratory, thoracic and mediastinal disorders
Pulmunary embolism
|
4.9%
3/61
|
4.8%
3/63
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.3%
2/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Pulmunary Oedema
|
3.3%
2/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
respiratory failure
|
3.3%
2/61
|
1.6%
1/63
|
|
Respiratory, thoracic and mediastinal disorders
acute pulmunary oedema
|
1.6%
1/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
chronic obstructive pulmunary disease
|
1.6%
1/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.6%
1/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.6%
1/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
1.6%
1/61
|
1.6%
1/63
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.6%
1/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
1.6%
1/61
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.00%
0/61
|
1.6%
1/63
|
|
Infections and infestations
Pneumonia
|
3.3%
2/61
|
1.6%
1/63
|
|
Infections and infestations
Urinary Tract Infection
|
1.6%
1/61
|
0.00%
0/63
|
|
Cardiac disorders
Cardiac Failure Acute
|
1.6%
1/61
|
0.00%
0/63
|
|
Cardiac disorders
Myocardial infarction
|
1.6%
1/61
|
0.00%
0/63
|
|
Cardiac disorders
Pleuropericarditis
|
1.6%
1/61
|
0.00%
0/63
|
|
Cardiac disorders
tachycardia
|
0.00%
0/61
|
1.6%
1/63
|
|
Gastrointestinal disorders
Pancreatitis
|
1.6%
1/61
|
0.00%
0/63
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
1/61
|
0.00%
0/63
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/61
|
1.6%
1/63
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/61
|
1.6%
1/63
|
|
Nervous system disorders
Cerebral Infarction
|
1.6%
1/61
|
0.00%
0/63
|
|
Nervous system disorders
Depressed Level Of Consciuosness
|
1.6%
1/61
|
0.00%
0/63
|
|
Nervous system disorders
Cerebral Ischemia
|
0.00%
0/61
|
3.2%
2/63
|
|
Nervous system disorders
Presyncope
|
0.00%
0/61
|
1.6%
1/63
|
|
Renal and urinary disorders
Renal Failure
|
3.3%
2/61
|
0.00%
0/63
|
|
Renal and urinary disorders
Uraniry Retention
|
0.00%
0/61
|
1.6%
1/63
|
|
Skin and subcutaneous tissue disorders
rash
|
1.6%
1/61
|
0.00%
0/63
|
|
Skin and subcutaneous tissue disorders
Skin Toxicity
|
1.6%
1/61
|
0.00%
0/63
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.6%
1/61
|
0.00%
0/63
|
|
Eye disorders
Eye Disorder
|
1.6%
1/61
|
0.00%
0/63
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
1.6%
1/61
|
0.00%
0/63
|
|
Investigations
Weight Decrease
|
1.6%
1/61
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscoloskeletal Pain
|
1.6%
1/61
|
0.00%
0/63
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ear Neoplasm
|
1.6%
1/61
|
0.00%
0/63
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma
|
0.00%
0/61
|
1.6%
1/63
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal Adenocarcinoma
|
0.00%
0/61
|
1.6%
1/63
|
|
Psychiatric disorders
Confusional State
|
1.6%
1/61
|
1.6%
1/63
|
|
General disorders
Pyrexia
|
0.00%
0/61
|
4.8%
3/63
|
|
General disorders
Chest Pain
|
0.00%
0/61
|
1.6%
1/63
|
|
Vascular disorders
Infarction
|
0.00%
0/61
|
1.6%
1/63
|
|
Vascular disorders
Peripheral Ischaemia
|
0.00%
0/61
|
1.6%
1/63
|
|
Vascular disorders
Vena Cava Thrombosis
|
0.00%
0/61
|
1.6%
1/63
|
|
Hepatobiliary disorders
Hepatic Cirrhosis
|
0.00%
0/61
|
1.6%
1/63
|
Other adverse events
| Measure |
ZD6474 (Gemcitabine), Vandetanib
n=61 participants at risk
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.
|
Placebo to Match ZD6474 (Gemcitabine), Vandetanib
n=63 participants at risk
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
|
|---|---|---|
|
General disorders
pyrexia
|
27.9%
17/61
|
27.0%
17/63
|
|
General disorders
Fatigue
|
23.0%
14/61
|
23.8%
15/63
|
|
General disorders
Asthenia
|
14.8%
9/61
|
20.6%
13/63
|
|
Respiratory, thoracic and mediastinal disorders
Dispnoea
|
21.3%
13/61
|
30.2%
19/63
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.8%
9/61
|
15.9%
10/63
|
|
Blood and lymphatic system disorders
PLT count decrease
|
11.5%
7/61
|
14.3%
9/63
|
|
Blood and lymphatic system disorders
Neutropenia
|
19.7%
12/61
|
19.0%
12/63
|
|
Blood and lymphatic system disorders
Anaemia
|
13.1%
8/61
|
22.2%
14/63
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.5%
7/61
|
6.3%
4/63
|
|
Gastrointestinal disorders
Diarrhoea
|
14.8%
9/61
|
14.3%
9/63
|
|
Gastrointestinal disorders
Nausea
|
11.5%
7/61
|
12.7%
8/63
|
|
Gastrointestinal disorders
Vomiting
|
6.6%
4/61
|
11.1%
7/63
|
|
Skin and subcutaneous tissue disorders
Rash
|
24.6%
15/61
|
7.9%
5/63
|
|
Metabolism and nutrition disorders
Anorexia
|
13.1%
8/61
|
27.0%
17/63
|
|
Metabolism and nutrition disorders
Hypokaliemia
|
3.3%
2/61
|
11.1%
7/63
|
|
General disorders
Mucosal Inflammation
|
6.6%
4/61
|
6.3%
4/63
|
|
General disorders
Oedema Peripheral
|
6.6%
4/61
|
19.0%
12/63
|
|
General disorders
Chest Pain
|
3.3%
2/61
|
23.8%
15/63
|
|
Respiratory, thoracic and mediastinal disorders
Pulmunary Embolism
|
6.6%
4/61
|
4.8%
3/63
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
6.6%
4/61
|
1.6%
1/63
|
|
Blood and lymphatic system disorders
Alanine Aminotransferase Increased
|
8.2%
5/61
|
1.6%
1/63
|
|
Blood and lymphatic system disorders
Neutrphil Count Decreased
|
8.2%
5/61
|
3.2%
2/63
|
|
Blood and lymphatic system disorders
Aspartate Aminotransferase Inctìreased
|
6.6%
4/61
|
1.6%
1/63
|
|
Gastrointestinal disorders
Constipation
|
3.3%
2/61
|
6.3%
4/63
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.6%
4/61
|
3.2%
2/63
|
|
Vascular disorders
Phlebitis
|
8.2%
5/61
|
4.8%
3/63
|
|
Psychiatric disorders
Depression
|
4.9%
3/61
|
6.3%
4/63
|
|
Psychiatric disorders
Insomnia
|
1.6%
1/61
|
6.3%
4/63
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER