Trial Outcomes & Findings for RAD001 With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced Large Cell Lung Cancer With Neuroendocrine Differentiation (NCT NCT01317615)
NCT ID: NCT01317615
Last Updated: 2016-03-30
Results Overview
Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST) to determine progression-free status. Complete response (CR): disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR): \> 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; Progressive disease (PD): \> 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm.
COMPLETED
PHASE4
49 participants
3 months
2016-03-30
Participant Flow
This was an open-label, single arm study.
Participant milestones
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Overall Study
STARTED
|
49
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
49
|
Reasons for withdrawal
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Overall Study
Disease progression
|
25
|
|
Overall Study
New cancer therapy
|
5
|
|
Overall Study
Death
|
6
|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Abnormal laboratory value(s)
|
1
|
|
Overall Study
Adverse Event
|
7
|
Baseline Characteristics
RAD001 With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced Large Cell Lung Cancer With Neuroendocrine Differentiation
Baseline characteristics by cohort
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 Participants
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Age, Continuous
|
62 Years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: All participants were included in the analysis.
Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST) to determine progression-free status. Complete response (CR): disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR): \> 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; Progressive disease (PD): \> 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm.
Outcome measures
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 Participants
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Percentage of Participants Progression-free
|
49.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants were included in the analysis.
Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST) to determine progression-free status. Complete response (CR) is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR) is \> 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; and Progressive disease (PD is: \> 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm.
Outcome measures
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 Participants
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Percentage of Participants Progression-free
|
8.2 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: All participants were included in the analysis.
ORR was defined as is the proportion of participants with a best overall response of CR or PR. CR is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response. PR is \> 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions.
Outcome measures
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 Participants
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Percentage of Participants With Overall Response Rate (ORR)
|
44.9 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: All participants were included in the analysis.
DCR was defined as is the percentage of participants with a best overall response of CR or PR or SD. Complete response (CR) is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR) is \> 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; and Progressive disease (PD is: \> 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm.
Outcome measures
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 Participants
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Percentage of Participants With Disease Control Rate (DCR)
|
73.5 Percentage of participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants were included in the analysis.
PFS was defined as the time from the date of start of treatment to date of event defined as the first documented progression or death due to any cause.
Outcome measures
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 Participants
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Progression Free Survival (PFS)
|
132 Days
Interval 97.0 to 181.0
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All participants were included in the analysis.
OS was defined as the time from date of start of treatment to date of death due to any cause.
Outcome measures
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 Participants
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Overall Survival (OS)
|
298 Days
Interval 207.0 to 351.0
|
Adverse Events
RAD001 Plus Paclitaxel/Carboplatin
Serious adverse events
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 participants at risk
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
2.0%
1/49
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
2.0%
1/49
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
2.0%
1/49
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
4.1%
2/49
|
|
Ear and labyrinth disorders
VERTIGO
|
2.0%
1/49
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
2.0%
1/49
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
4.1%
2/49
|
|
Gastrointestinal disorders
COLITIS
|
2.0%
1/49
|
|
Gastrointestinal disorders
CONSTIPATION
|
4.1%
2/49
|
|
Gastrointestinal disorders
DIARRHOEA
|
2.0%
1/49
|
|
Gastrointestinal disorders
GASTRITIS
|
2.0%
1/49
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
2.0%
1/49
|
|
Gastrointestinal disorders
NAUSEA
|
2.0%
1/49
|
|
General disorders
FATIGUE
|
2.0%
1/49
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
10.2%
5/49
|
|
General disorders
MULTI-ORGAN FAILURE
|
2.0%
1/49
|
|
General disorders
PAIN
|
4.1%
2/49
|
|
Hepatobiliary disorders
ACUTE HEPATIC FAILURE
|
2.0%
1/49
|
|
Hepatobiliary disorders
HEPATOMEGALY
|
2.0%
1/49
|
|
Infections and infestations
CLOSTRIDIAL INFECTION
|
2.0%
1/49
|
|
Infections and infestations
EMPYEMA
|
2.0%
1/49
|
|
Infections and infestations
EPIDIDYMITIS
|
2.0%
1/49
|
|
Infections and infestations
GASTROENTERITIS
|
2.0%
1/49
|
|
Infections and infestations
INFECTION
|
2.0%
1/49
|
|
Infections and infestations
PNEUMONIA
|
6.1%
3/49
|
|
Infections and infestations
PYOPNEUMOTHORAX
|
2.0%
1/49
|
|
Infections and infestations
SEPSIS
|
4.1%
2/49
|
|
Infections and infestations
SINUSITIS
|
2.0%
1/49
|
|
Investigations
C-REACTIVE PROTEIN INCREASED
|
2.0%
1/49
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
4.1%
2/49
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
4.1%
2/49
|
|
Musculoskeletal and connective tissue disorders
PAIN IN JAW
|
2.0%
1/49
|
|
Musculoskeletal and connective tissue disorders
SPINAL PAIN
|
2.0%
1/49
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BENIGN NEOPLASM OF THYROID GLAND
|
2.0%
1/49
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BRONCHIAL CARCINOMA
|
2.0%
1/49
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
2.0%
1/49
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO CENTRAL NERVOUS SYSTEM
|
2.0%
1/49
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PARANEOPLASTIC SYNDROME
|
2.0%
1/49
|
|
Nervous system disorders
SCIATICA
|
2.0%
1/49
|
|
Nervous system disorders
VOCAL CORD PARESIS
|
2.0%
1/49
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
10.2%
5/49
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
2.0%
1/49
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
6.1%
3/49
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX
|
6.1%
3/49
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
2.0%
1/49
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
2.0%
1/49
|
Other adverse events
| Measure |
RAD001 Plus Paclitaxel/Carboplatin
n=49 participants at risk
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
|
|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
28.6%
14/49
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
14.3%
7/49
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
20.4%
10/49
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
16.3%
8/49
|
|
Eye disorders
VISUAL IMPAIRMENT
|
6.1%
3/49
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
6.1%
3/49
|
|
Gastrointestinal disorders
CONSTIPATION
|
18.4%
9/49
|
|
Gastrointestinal disorders
DIARRHOEA
|
20.4%
10/49
|
|
Gastrointestinal disorders
DYSPHAGIA
|
6.1%
3/49
|
|
Gastrointestinal disorders
NAUSEA
|
26.5%
13/49
|
|
Gastrointestinal disorders
STOMATITIS
|
16.3%
8/49
|
|
General disorders
ASTHENIA
|
8.2%
4/49
|
|
General disorders
CHEST PAIN
|
6.1%
3/49
|
|
General disorders
FATIGUE
|
34.7%
17/49
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
6.1%
3/49
|
|
General disorders
MUCOSAL INFLAMMATION
|
16.3%
8/49
|
|
General disorders
OEDEMA PERIPHERAL
|
14.3%
7/49
|
|
General disorders
PAIN
|
12.2%
6/49
|
|
General disorders
PERIPHERAL SWELLING
|
8.2%
4/49
|
|
General disorders
PYREXIA
|
6.1%
3/49
|
|
Infections and infestations
INFECTION
|
8.2%
4/49
|
|
Investigations
WEIGHT DECREASED
|
16.3%
8/49
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
6.1%
3/49
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
20.4%
10/49
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
10.2%
5/49
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
10.2%
5/49
|
|
Musculoskeletal and connective tissue disorders
GROWING PAINS
|
6.1%
3/49
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
6.1%
3/49
|
|
Nervous system disorders
HEADACHE
|
12.2%
6/49
|
|
Nervous system disorders
HYPOAESTHESIA
|
6.1%
3/49
|
|
Nervous system disorders
PARAESTHESIA
|
14.3%
7/49
|
|
Nervous system disorders
POLYNEUROPATHY
|
18.4%
9/49
|
|
Psychiatric disorders
INSOMNIA
|
6.1%
3/49
|
|
Psychiatric disorders
SLEEP DISORDER
|
10.2%
5/49
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
16.3%
8/49
|
|
Respiratory, thoracic and mediastinal disorders
DYSPHONIA
|
6.1%
3/49
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
26.5%
13/49
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
6.1%
3/49
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
24.5%
12/49
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
8.2%
4/49
|
|
Skin and subcutaneous tissue disorders
RASH
|
14.3%
7/49
|
Additional Information
Study Director
Novartis
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER