Carcinoma, Non-Squamous Non-Small-Cell Lung Cancer
Conditions
Keywords
Non-small-cell-lung cancer, carboplatin, paclitaxel, VEGF, monoclonal antibody
Brief summary
A 2-part study to examine safety, tolerability and pharmacokinetics (part 1), and anti-tumour effects (part 2), of CDP791 combined with carboplatin and paclitaxel.
Detailed description
This is a two part study to investigate the safety and anti-tumour effects of standard chemotherapy, plus an investigational drug (CDP791), in patients with advanced non small cell lung cancer. In part one, patients receive carboplatin and paclitaxel chemotherapy together with one of 2 doses of CDP791. The main aim of this part is to investigate safety and tolerability of carboplatin/paclitaxel plus CDP791. If part one confirms that the combination of drugs is safe and well tolerated, 156 patients will enter part 2. They will be randomized to receive either carboplatin/paclitaxel (C/P) alone, or C/P plus one of 2 doses of CDP791. The main aim of this part of the study is to compare the anti-tumor effects of CDP791 plus C/T with those of C/T alone. Participants will receive up to six cycles of chemotherapy with or without CDP791. Those whose disease stabilizes, or responds, will be eligible to continue to receive CDP791. Participants in the C/T alone arm whose disease progresses will be eligible to receive CDP791 monotherapy. Participants will be followed up longterm, so that survival can be measured.
Interventions
DRUGCarboplatin
10mg/mL vial AUC6. Dosed intravenously over 15-30 minutes immediately following paclitaxel, Day 0 of each cycle. Each cycle to be repeated every three weeks for a maximum of six cycles.
DRUGPaclitaxel
6mg/mL vial 200 mg/m2 iv over three hours, Day 0. Each cycle to be repeated every 3 weeks for a maximum of 6 cycles.
DRUGCDP791 10mg/kg
CDP791 20mg/mL vial CDP791 diluted (10mg/kg or 20mg/kg) in 0.9% saline will be given as a 200mL iv infusion over approximately 60 minutes following administration of standard chemotherapy.
DRUGCDP791 20mg/kg
CDP791 20mg/kg CDP791 diluted (10mg/kg or 20mg/kg) in 0.9% saline will be given as a 200mL iv infusion over approximately 60 minutes following administration of standard chemotherapy.
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: * Male and female subjects with Stage IIIb (with malignant pleural effusion or if no pleural effusion is present subjects who are not candidates for combined modality therapy), Stage IV, or recurrent non-squamous, non-small-cell lung carcinoma. * The subject must be aged 18 years or above. * The subject must have ECOG performance status of 0 or 1 and a life expectancy of at least three months. * Subjects will have measurable disease. * The subject must be able to understand the information provided to them and to give written informed consent. * Female subjects must be either postmenopausal, surgically sterilized, or using a method of contraception judged reliable by the Investigator. * Male subjects must be using a method of contraception judged reliable by the Investigator.
Exclusion criteria
* Subjects with squamous cell lung carcinoma. * Subjects with lung lesions located centrally in the chest that involve major blood vessels. * Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous malignancies are eligible provided that they have been disease free for five years or more. * Presence of additional major chronic disease such as hepatic or renal dysfunction, cardiac dysfunction, peripheral vascular disease, evidence of a myocardial infarction within six months of Screening visit, tuberculosis or epilepsy. * Subjects known to be infected with hepatitis B or C virus or HIV 1 or 2. * Any evidence of serious active infection (ie requiring an iv antibiotic or antiviral agent).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate (RR) | 24 weeks | Participants are evaluated for response using Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse P et al; 2000). The tumor response rate is calculated as the total number of subjects whose best overall response is a complete response (CR)= disappearance of all target lesions; or a partial response (PR) = \>=30 % decrease in the sum of the longest diameter of target lesions, divided by the number of randomized subjects (RS): (CR + PR) / RS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 57 weeks | Progression free survival (PFS) is defined as time from date of randomization until the date progressive disease (PD) is first recorded or until death, whichever is first. |
| Time to Treatment Failure | Up to 57 weeks | Time to treatment failure (TTF) is defined as the time from date of randomization until the date of progression, death or, for subjects who discontinued treatment for toxicity reason, their last dosing date, whichever occurs first. |
| Overall Survival | Up to 57 weeks | Overall survival is defined as the time from date of randomization until the date of death. |
| Duration of Overall Response | Up to 57 weeks | The duration of overall response is measured from the time measurement criteria are first met for complete response (CR) or partial response (PR), whichever is recorded first, until the first date of documented progressive disease or death. |
| Time to Response | Week 24 | Time to response is defined as the time from the first dose of study therapy until measurement criteria are first met for complete response or partial response (whichever is recorded first). |
Countries
Hungary, Poland, Russia
Participant flow
Recruitment details
The study started to enroll patients in August 2005 and concluded in June 2009. Across Part I (dose escalation) and Part II (Open Label randomized) of the study, 165 subjects were analyzed. Part II was opened for 156 response-evaluable subjects.
Pre-assignment details
Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin/Paclitaxel Carboplatin and paclitaxel alone | 50 |
| Carboplatin/Paclitaxel/CDP791 10mg Carboplatin and paclitaxel plus CDP791 10mg/kg | 53 |
| Carboplatin/Paclitaxel/CDP791 20mg Carboplatin and paclitaxel plus CDP791 20mg/kg | 53 |
| Total Title | 156 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Chemotherapy Period | Adverse Event | 9 | 4 | 5 |
| Chemotherapy Period | Death | 1 | 3 | 3 |
| Chemotherapy Period | Investigator decision | 0 | 0 | 1 |
| Chemotherapy Period | Lack of Efficacy | 4 | 5 | 6 |
| Chemotherapy Period | Lost to Follow-up | 1 | 0 | 1 |
| Chemotherapy Period | Patient condition worsened | 1 | 0 | 0 |
| Chemotherapy Period | Progression of Disease | 6 | 8 | 4 |
| Chemotherapy Period | Protocol Violation | 1 | 1 | 0 |
| Chemotherapy Period | Withdrawal by Subject | 5 | 1 | 0 |
| Monotherapy Period | Adverse Event | 1 | 0 | 5 |
| Monotherapy Period | Death | 2 | 0 | 1 |
| Monotherapy Period | Lack of Efficacy | 7 | 16 | 10 |
| Monotherapy Period | Patient decision | 0 | 1 | 1 |
| Monotherapy Period | Progression of Disease | 5 | 11 | 12 |
| Monotherapy Period | Protocol Violation | 0 | 1 | 0 |
| Monotherapy Period | Study personel decision | 0 | 0 | 1 |
| Monotherapy Period | Withdrawal by Subject | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Carboplatin/Paclitaxel | Carboplatin/Paclitaxel/CDP791 10mg | Carboplatin/Paclitaxel/CDP791 20mg | Total Title |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 18 Participants | 13 Participants | 51 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 35 Participants | 40 Participants | 105 Participants |
| Age, Continuous | 61.58 years STANDARD_DEVIATION 10.69 | 60.70 years STANDARD_DEVIATION 10.01 | 58.25 years STANDARD_DEVIATION 9.38 | 60.15 years STANDARD_DEVIATION 10.06 |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 29 Participants | 70 Participants |
| Sex: Female, Male Male | 30 Participants | 32 Participants | 24 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 30 / 50 | 72 / 115 | 39 / 56 | 33 / 59 |
| other Total, other adverse events | 44 / 50 | 110 / 115 | 54 / 56 | 56 / 56 |
| serious Total, serious adverse events | 18 / 50 | 36 / 115 | 18 / 56 | 18 / 59 |
Outcome results
Primary
Tumor Response Rate (RR)
Participants are evaluated for response using Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse P et al; 2000). The tumor response rate is calculated as the total number of subjects whose best overall response is a complete response (CR)= disappearance of all target lesions; or a partial response (PR) = \>=30 % decrease in the sum of the longest diameter of target lesions, divided by the number of randomized subjects (RS): (CR + PR) / RS.
Time frame: 24 weeks
Population: All Randomized Part II Subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carboplatin/Paclitaxel (Randomized Part II SjS) | Tumor Response Rate (RR) | Complete responder | 0 percentage of participants |
| Carboplatin/Paclitaxel (Randomized Part II SjS) | Tumor Response Rate (RR) | Partial responder | 20 percentage of participants |
| Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS) | Tumor Response Rate (RR) | Partial responder | 26.4 percentage of participants |
| Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS) | Tumor Response Rate (RR) | Complete responder | 0 percentage of participants |
| Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS) | Tumor Response Rate (RR) | Complete responder | 0 percentage of participants |
| Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS) | Tumor Response Rate (RR) | Partial responder | 22.6 percentage of participants |
| Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS) | Tumor Response Rate (RR) | Complete responder | 0 percentage of participants |
| Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS) | Tumor Response Rate (RR) | Partial responder | 30.2 percentage of participants |
p-value: =0.38495% CI: [-7.7, 20.5]Cochran-Mantel-Haenszel
p-value: =0.40995% CI: [-7.7, 20.5]Cochran-Mantel-Haenszel
p-value: =0.74495% CI: [-13.5, 18.8]Chi-squared
p-value: =0.78395% CI: [-13.5, 18.8]Cochran-Mantel-Haenszel
p-value: =0.23495% CI: [-6.8, 27.2]Chi-squared
p-value: =0.22895% CI: [-6.8, 27.2]Cochran-Mantel-Haenszel
Secondary
Duration of Overall Response
The duration of overall response is measured from the time measurement criteria are first met for complete response (CR) or partial response (PR), whichever is recorded first, until the first date of documented progressive disease or death.
Time frame: Up to 57 weeks
Population: The duration of overall response was computed for subjects only, whose best response was either PR or CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel (Randomized Part II SjS) | Duration of Overall Response | 21.14 weeks |
| Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS) | Duration of Overall Response | 21.14 weeks |
| Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS) | Duration of Overall Response | 21.14 weeks |
| Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS) | Duration of Overall Response | 18.00 weeks |
Secondary
Overall Survival
Overall survival is defined as the time from date of randomization until the date of death.
Time frame: Up to 57 weeks
Population: All Randomized Part II Subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel (Randomized Part II SjS) | Overall Survival | 36.14 weeks |
| Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS) | Overall Survival | 47.14 weeks |
| Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS) | Overall Survival | 46.57 weeks |
| Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS) | Overall Survival | 47.57 weeks |
Secondary
Progression Free Survival (PFS)
Progression free survival (PFS) is defined as time from date of randomization until the date progressive disease (PD) is first recorded or until death, whichever is first.
Time frame: Up to 57 weeks
Population: All Randomized Part II Subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel (Randomized Part II SjS) | Progression Free Survival (PFS) | 24.14 weeks |
| Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS) | Progression Free Survival (PFS) | 26.86 weeks |
| Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS) | Progression Free Survival (PFS) | 26.86 weeks |
| Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS) | Progression Free Survival (PFS) | 25.43 weeks |
Secondary
Time to Response
Time to response is defined as the time from the first dose of study therapy until measurement criteria are first met for complete response or partial response (whichever is recorded first).
Time frame: Week 24
Population: The time to response was computed for subjects only, whose best response was either PR or CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel (Randomized Part II SjS) | Time to Response | 8.57 weeks |
| Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS) | Time to Response | 9.14 weeks |
| Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS) | Time to Response | 11.86 weeks |
| Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS) | Time to Response | 9.00 weeks |
Secondary
Time to Treatment Failure
Time to treatment failure (TTF) is defined as the time from date of randomization until the date of progression, death or, for subjects who discontinued treatment for toxicity reason, their last dosing date, whichever occurs first.
Time frame: Up to 57 weeks
Population: All Randomized Part II Subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel (Randomized Part II SjS) | Time to Treatment Failure | 13.21 weeks |
| Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS) | Time to Treatment Failure | 21.71 weeks |
| Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS) | Time to Treatment Failure | 18.43 weeks |
| Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS) | Time to Treatment Failure | 24.29 weeks |