Prostate Cancer
Conditions
Keywords
Prostate cancer, Infusion, Carlumab, CNTO 888
Brief summary
The purpose of this study is to determine the safety and effectiveness of the study drug carlumab in participants with metastatic castrate-resistant prostate cancer (cancer of the gland that makes fluid that aids movement of sperm).
Detailed description
This is an open-label (all people know the identity of the intervention), multicenter trial (conducted in more than one center) in participants with metastatic castrate-resistant prostate cancer. The trial consists of 3 phases: screening period, treatment period of approximately 4 months, and a follow-up period (Week 1, 4, 8 and 12 after the last dose) of up to 12 weeks after the administration of last dose. The participants will receive carlumab at the dose of 15 milligram/kilogram (mg/kg) by intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) at a constant rate over a 90 minute period once every 2 weeks until disease progression. Efficacy of the participants will be primarily evaluated by composite response. Participants' safety will be monitored throughout the study.
Interventions
DRUGCarlumab
Carlumab diluted in 5 percent (%) dextrose administered at the dose of 15 milligram per kilogram (mg/kg) by intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) at a constant rate over a 90 minute period once every 2 weeks until disease progression.
Sponsors
Centocor Research & Development, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological documentation of adenocarcinoma of the prostate * Received at least 1 but no more than 2 prior docetaxel-based chemotherapy regimens and had disease progression following the last therapy * Serum prostate specific antigen (PSA) greater than or equal to 5.0 nanogram/milliliter (ng/ml) within 4 weeks prior to the first dose of study agent * Orchiectomy (surgery to remove one or both testicles) or testosterone less than 50 nanogram/deciliter by means of pharmacological/chemical castration within 4 weeks prior to the first dose of study agent * At least 6 weeks from prior docetaxel chemotherapy regimen to first dose of study agent
Exclusion criteria
* Experience a hormonal treatment withdrawal response (including a lowering of PSA that was previously rising or symptomatic improvement) * Known or symptomatic Central Nervous System metastases * Residual toxicities resulting from previous therapy that are Grade 2 or more (except for alopecia) * Known allergies, hypersensitivity, or intolerance to carlumab or its excipients or clinically significant reactions to chimeric or human proteins * Vaccinated with live, attenuated vaccines within 4 weeks prior to the first dose of study agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Composite Response | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | The composite response is measured by change from Baseline in skeletal lesions, extra-skeletal lesions, and prostate specific antigen (PSA) values. A participant is considered to have composite response, if 1 of the following responses occurs after the first dose of carlumab: (1) Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST), (2) PSA response at 12 weeks and absence of skeletal and extra-skeletal progression or (3) Stable disease at 24 weeks defined as the absence of PSA, skeletal, or extra-skeletal progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Tumor Response | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | Objective response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response. |
| Progression-Free Survival (PFS) | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | The PFS is defined as the time from the date of initiation of study treatment to the date of initial documented skeletal or extra-skeletal progressive disease, or date of death, whichever occurs first. A participant is considered to have extra-skeletal disease progression if the disease has progressed as per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. A participant is considered to have skeletal disease progression if they have 1 post-baseline bone scan demonstrating 2 or more new skeletal lesions compared to Baseline and confirmed by a second bone scan 6 to 12 weeks later or with evidence of clinical progression. |
| Overall Survival (OS) | Week 8, 12, every 12 weeks up to 1 year after last dose of carlumab | The OS is defined as the time from the date of initiation of study treatment to death due to any cause. Participants were followed for 1 year after the last administration of carlumab for survival or until the end of study, whichever occurs first. For participants with unknown survival status as of the data cutoff date, OS was censored at the last date that the participant was known to be alive. |
| Percentage of Participants With Prostate Specific Antigen (PSA) Response | Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab | The PSA response for participants with elevated PSA levels at Baseline (more than or equal to 5 nanogram per milliliter (ng/mL) is defined as at least a 50% reduction in PSA from the Baseline value, confirmed by a second PSA value measurement 3 or more weeks later. |
| Percentage of Participants With Urinary Crosslinked N-Telopeptide of Type I Collagen (NTx) Response | Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab | Urinary NTx response for participants with elevated NTx level at Baseline (more than or equal to 50 nanomole per millimole (nmol/mmol)) is defined as a 30% reduction from Baseline NTx value, confirmed by a second NTx value 3 or more weeks later. |
| Percentage of Participants With Pain Response | Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4 after last dose of carlumab | Pain response is defined as 2-point decrease from Baseline in 'worst pain' intensity score (item 3) on the Brief Pain Inventory (BPI) questionnaire. The BPI is a nine-item questionnaire with 0 to 10 numeric rating scales in response to each item, where 0=No pain and 10=Pain as bad as you can imagine. Measure can be scored by item, with lower scores being indicative of less pain or pain interference. |
| Duration of Radiologic Response | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response. |
| Minimum Observed Serum Concentration (Cmin) | Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose | — |
| Maximum Observed Serum Concentration (Cmax) | Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose | The maximum observed analyte concentration was measured. |
| Area Under the Serum Concentration Versus Time Curve Between 0 And 14 Days (AUC 0-14d) | Pre-dose, at the end of infusion, 2, 4 hr and 1 week after end of infusion for the first dose | — |
| Half-life (t1/2) | Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose | The time measured for the serum concentration to decrease by one half. |
| Time to Radiologic Response | Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab | Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Status Score | Up to 2 weeks before first dose, pre-infusion, Week 4 after last dose of carlumab | A worsening in ECOG performance status score was defined as greater than or equal to 1-point increase from Baseline. Time to worsening is defined as the number of days from first dose to the first day of worsening in ECOG score, or death, whichever occurred first. ECOG is a 5-point scale 0=Fully active, 1=Ambulatory, carry out work of sedentary nature, 2=Ambulatory, capable of all selfcare, 3=Capable of limited selfcare, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, no selfcare, totally confined to bed or chair, 5=Dead. |
Countries
Belgium, Russia, United Kingdom, United States
Participant flow
Pre-assignment details
16 out of 62 participants, who signed informed consent, were deemed ineligible for the study during screening because of screening failure, serious adverse events, unavailability of carlumab at the site and withdrawal of consent.
Participants by arm
| Arm | Count |
|---|---|
| Carlumab Carlumab diluted in 5 percent (%) dextrose administered at the dose of 15 milligram per kilogram (mg/kg) by intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) at a constant rate over a 90 minute period once every 2 weeks until disease progression. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Progressive Disease | 30 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Refusal To Receive Study Agent | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Carlumab |
|---|---|
| Age Continuous | 67.5 Years STANDARD_DEVIATION 7.95 |
| Region of Enrollment Belgium | 11 participants |
| Region of Enrollment Russian Federation | 10 participants |
| Region of Enrollment United Kingdom | 18 participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 46 |
| serious Total, serious adverse events | 20 / 46 |
Outcome results
Primary
Percentage of Participants With Composite Response
The composite response is measured by change from Baseline in skeletal lesions, extra-skeletal lesions, and prostate specific antigen (PSA) values. A participant is considered to have composite response, if 1 of the following responses occurs after the first dose of carlumab: (1) Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST), (2) PSA response at 12 weeks and absence of skeletal and extra-skeletal progression or (3) Stable disease at 24 weeks defined as the absence of PSA, skeletal, or extra-skeletal progression.
Time frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab and had at least 1 post-baseline disease evaluation. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carlumab | Percentage of Participants With Composite Response | CR or PR | 0.0 Percentage of participants |
| Carlumab | Percentage of Participants With Composite Response | PSA response | 0.0 Percentage of participants |
| Carlumab | Percentage of Participants With Composite Response | Stable disease | 2.4 Percentage of participants |
Secondary
Area Under the Serum Concentration Versus Time Curve Between 0 And 14 Days (AUC 0-14d)
Time frame: Pre-dose, at the end of infusion, 2, 4 hr and 1 week after end of infusion for the first dose
Population: Analysis population included all the participants who received at least 1 administration of carlumab except those whose serum samples were missing at the end of infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carlumab | Area Under the Serum Concentration Versus Time Curve Between 0 And 14 Days (AUC 0-14d) | 1635.67 mcg*day/mL | Standard Deviation 528.925 |
Secondary
Duration of Radiologic Response
Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Time frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab. No data was available for this endpoint as no participant achieved CR or PR.
Secondary
Half-life (t1/2)
The time measured for the serum concentration to decrease by one half.
Time frame: Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose
Population: Analysis population included all the participants who received at least 1 administration of carlumab except those whose serum samples were missing at the end of infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carlumab | Half-life (t1/2) | 13.32 Days |
Secondary
Maximum Observed Serum Concentration (Cmax)
The maximum observed analyte concentration was measured.
Time frame: Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose
Population: Analysis population included all the participants who received at least 1 administration of carlumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carlumab | Maximum Observed Serum Concentration (Cmax) | 320.27 mcg/mL | Standard Deviation 75.712 |
Secondary
Minimum Observed Serum Concentration (Cmin)
Time frame: Pre-dose and at the end of infusion for each Dose; 2, 4 hour (hr) and 1 week after Dose 1; 2 hr after Dose 4; Week 1, 4, 8 and 12 post-last dose
Population: Analysis population included all the participants who received at least 1 administration of carlumab. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carlumab | Minimum Observed Serum Concentration (Cmin) | 91.82 microgram/milliliter (mcg/mL) | Standard Deviation 87.24 |
Secondary
Overall Survival (OS)
The OS is defined as the time from the date of initiation of study treatment to death due to any cause. Participants were followed for 1 year after the last administration of carlumab for survival or until the end of study, whichever occurs first. For participants with unknown survival status as of the data cutoff date, OS was censored at the last date that the participant was known to be alive.
Time frame: Week 8, 12, every 12 weeks up to 1 year after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carlumab | Overall Survival (OS) | 309.0 Days |
Secondary
Percentage of Participants With Objective Tumor Response
Objective response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Time frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab and had a measurable, non-measurable or bone lesion at Baseline and had at least 1 post-treatment tumor evaluation. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carlumab | Percentage of Participants With Objective Tumor Response | CR | 0.0 Percentage of participants |
| Carlumab | Percentage of Participants With Objective Tumor Response | PR | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Pain Response
Pain response is defined as 2-point decrease from Baseline in 'worst pain' intensity score (item 3) on the Brief Pain Inventory (BPI) questionnaire. The BPI is a nine-item questionnaire with 0 to 10 numeric rating scales in response to each item, where 0=No pain and 10=Pain as bad as you can imagine. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
Time frame: Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4 after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab, had Baseline BPI 'worst pain' intensity score (item 3) more than or equal to 2, and at least 1 post-treatment pain evaluation. Participants with disease progression were considered to be evaluable, regardless of the post-dose evaluation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carlumab | Percentage of Participants With Pain Response | During stable use of analgesic medication | 32.3 Percentage of participants |
| Carlumab | Percentage of Participants With Pain Response | At any time | 38.7 Percentage of participants |
Secondary
Percentage of Participants With Prostate Specific Antigen (PSA) Response
The PSA response for participants with elevated PSA levels at Baseline (more than or equal to 5 nanogram per milliliter (ng/mL) is defined as at least a 50% reduction in PSA from the Baseline value, confirmed by a second PSA value measurement 3 or more weeks later.
Time frame: Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab and had a Baseline PSA more than or equal to 5 ng/mL and at least 1 post-treatment PSA measurement. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carlumab | Percentage of Participants With Prostate Specific Antigen (PSA) Response | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Urinary Crosslinked N-Telopeptide of Type I Collagen (NTx) Response
Urinary NTx response for participants with elevated NTx level at Baseline (more than or equal to 50 nanomole per millimole (nmol/mmol)) is defined as a 30% reduction from Baseline NTx value, confirmed by a second NTx value 3 or more weeks later.
Time frame: Up to 2 weeks before first dose, every 4 weeks after first dose, Week 4, 8, 12 after the last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab and had elevated urinary NTx level at Baseline (more than or equal to 50 nmol/mmol) and at least 1 post-treatment urinary NTx measurement. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carlumab | Percentage of Participants With Urinary Crosslinked N-Telopeptide of Type I Collagen (NTx) Response | 0.0 Percentage of participants |
Secondary
Progression-Free Survival (PFS)
The PFS is defined as the time from the date of initiation of study treatment to the date of initial documented skeletal or extra-skeletal progressive disease, or date of death, whichever occurs first. A participant is considered to have extra-skeletal disease progression if the disease has progressed as per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. A participant is considered to have skeletal disease progression if they have 1 post-baseline bone scan demonstrating 2 or more new skeletal lesions compared to Baseline and confirmed by a second bone scan 6 to 12 weeks later or with evidence of clinical progression.
Time frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carlumab | Progression-Free Survival (PFS) | 81.0 Days |
Secondary
Time to Radiologic Response
Radiologic response based on assessment of confirmed CR or PR according to RECIST. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30% decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
Time frame: Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab. No data was available for this endpoint as no participant achieved CR or PR.
Other Pre-specified
Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Status Score
A worsening in ECOG performance status score was defined as greater than or equal to 1-point increase from Baseline. Time to worsening is defined as the number of days from first dose to the first day of worsening in ECOG score, or death, whichever occurred first. ECOG is a 5-point scale 0=Fully active, 1=Ambulatory, carry out work of sedentary nature, 2=Ambulatory, capable of all selfcare, 3=Capable of limited selfcare, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, no selfcare, totally confined to bed or chair, 5=Dead.
Time frame: Up to 2 weeks before first dose, pre-infusion, Week 4 after last dose of carlumab
Population: Analysis population included all the participants who received at least 1 administration of carlumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carlumab | Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Status Score | 86.0 Days |