Prostatic Neoplasms
Conditions
Keywords
Prostatic neoplasms, CNTO 95, Intetumumab, Docetaxel, Prednisone
Brief summary
The purpose of this study is to assess the effects of intetumumab when given in combination with docetaxel and prednisone to participants with metastatic (spread of cancer cells from one part of the body to another) hormone-refractory (not responding to treatment) prostate cancer (abnormal tissue that grows and spreads in the body until it kills).
Detailed description
This is a multicenter (when more than one hospital or medical school team work on a medical research study), randomized (the study drug is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives) study of intetumumab in combination with docetaxel and prednisone for the first-line treatment of participants with metastatic hormone-refractory prostate cancer. There will be 2 study groups. One group will receive intetumumab in combination with docetaxel and prednisone (study treatment) and the other group will receive placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) matching to intetumumab in combination with docetaxel and prednisone (control treatment). The duration of treatment will be 6 months. Participants who respond to treatment with stable disease or better will receive extended treatment until disease progression (disease worsening) or for an additional 6 months, whichever occurs first. Treatment can be further continued with the sponsor's discretion after receiving 6 months of extended treatment, if participant response to the treatment (with stable disease, partial response, or complete response). Participants who have confirmed progressive disease while receiving study treatment may have their treatment unblinded (participants will know the name of drug which was given to them), if they wish to be considered for alternative treatment. Participants who were receiving the control treatment will be considered to have completed the study treatment, and will have the option to receive alternative treatment. Alternative treatment will either be intetumumab along with docetaxel and prednisone or intetumumab alone. Participants' safety will be monitored throughout the study.
Interventions
DRUGDocetaxel
Docetaxel 75 mg/m\^2 as intravenous infusion every 3 weeks.
DRUGPrednisone
Prednisone 5 mg orally twice daily.
BIOLOGICALIntetumumab
Intetumumab 10 mg/kg as intravenous infusion every week for initial 6 weeks, then every 3 weeks.
DRUGPlacebo
Placebo matching to intetumumab, as intravenous infusion every week for initial 6 weeks, then every 3 weeks.
Sponsors
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed cancer of the prostate * Evidence of metastatic disease * Have a life expectancy greater than 12 weeks * Have at least 4 weeks from previous major surgery to date of first study agent given * Have progressive hormone-refractory disease after orchiectomy or gonadotropin-releasing hormone analog and/or antiandrogen treatment within 6 months prior to the first study agent administration
Exclusion criteria
* Have known Central Nervous System metastases (cancerous tumors that have spread to the brain from somewhere else in the body) * Had prior systemic non-hormonal therapy for hormone refractory prostate cancer * Have known Human Immunodeficiency Virus (HIV, a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person) seropositivity or known hepatitis B or C infection * Have planned major surgery during the study * Have taken any over-the-counter (medicine that can be bought without a prescription) or herbal treatment for prostate cancer within 4 weeks prior to the first study treatment administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline up to 6 months after last dose of study treatment, assessed up to 551 days | The PFS was assessed as median number of days from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Best Overall Response (OR) | Baseline up to 6 months after last dose of study treatment, assessed up to 551 days | Number of participants with best OR is based on assessment of confirmed complete response (CR) or confirmed partial response (PR). Confirmed CR is defined as disappearance of all target lesions. Confirmed PR is defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response. |
| Number of Participants With Prostate Specific Antigen (PSA) Response | Baseline up to 6 months after last dose of study treatment or early withdrawal, assessed up to 601 days | The PSA response is defined as at least a 50 percent decrease in PSA below the baseline value, confirmed by a second PSA value greater than or equal to 6 weeks later. A participant was considered to be a PSA responder if and only if the response occurs prior to PSA progression (increase of at least 25 percent and an increase of 5 nanogram per milliliter from the lowest observed PSA value since initiation of treatment, to be confirmed greater than or equal to 3 weeks later). |
| Overall Survival | Baseline until death (up to 887 days) | Overall Survival is defined as the time from the date of randomization to death due to any cause. For participants who were alive at the time of analysis, overall survival was censored at the last contact date. |
| Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Baseline, Week 6, 7, 10 and 13 | Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. |
| Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Baseline, Week 6, 7, 10 and 13 | Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. |
| Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Baseline, Week 6, 7, 10 and 13 | Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. |
Countries
Austria, Belgium, Germany, India, Netherlands, Poland, Russia, South Africa, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel + Prednisone + Placebo Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m\^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone. | 65 |
| Docetaxel + Prednisone + Intetumumab Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m\^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. | 66 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 9 |
| Overall Study | Death | 3 | 3 |
| Overall Study | Disease Progression | 9 | 18 |
| Overall Study | Other | 5 | 3 |
| Overall Study | Physician Decision | 7 | 6 |
| Overall Study | Sponsor decision | 14 | 9 |
| Overall Study | Withdrawal by Subject | 5 | 14 |
Baseline characteristics
| Characteristic | Docetaxel + Prednisone + Intetumumab | Total | Docetaxel + Prednisone + Placebo |
|---|---|---|---|
| Age Continuous | 66.3 Years STANDARD_DEVIATION 7.51 | 66.7 Years STANDARD_DEVIATION 8.13 | 67.2 Years STANDARD_DEVIATION 8.74 |
| Region of Enrollment AUSTRIA | 2 participants | 5 participants | 3 participants |
| Region of Enrollment BELGIUM | 9 participants | 19 participants | 10 participants |
| Region of Enrollment GERMANY | 14 participants | 33 participants | 19 participants |
| Region of Enrollment INDIA | 10 participants | 21 participants | 11 participants |
| Region of Enrollment NETHERLANDS | 5 participants | 7 participants | 2 participants |
| Region of Enrollment POLAND | 10 participants | 23 participants | 13 participants |
| Region of Enrollment RUSSIAN FEDERATION | 12 participants | 16 participants | 4 participants |
| Region of Enrollment SOUTH AFRICA | 0 participants | 1 participants | 1 participants |
| Region of Enrollment UNITED KINGDOM | 1 participants | 2 participants | 1 participants |
| Region of Enrollment UNITED STATES | 3 participants | 4 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 66 Participants | 131 Participants | 65 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 59 / 65 | 59 / 66 | 2 / 2 | 6 / 9 |
| serious Total, serious adverse events | 23 / 65 | 24 / 66 | 1 / 2 | 4 / 9 |
Outcome results
Primary
Progression-Free Survival (PFS)
The PFS was assessed as median number of days from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.
Time frame: Baseline up to 6 months after last dose of study treatment, assessed up to 551 days
Population: Efficacy population included all participants randomly assigned to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel + Prednisone + Placebo | Progression-Free Survival (PFS) | 336.0 Days |
| Docetaxel + Prednisone + Intetumumab | Progression-Free Survival (PFS) | 232.0 Days |
p-value: 0.01495% CI: [1.112, 2.686]Log Rank
Secondary
Number of Participants With Best Overall Response (OR)
Number of participants with best OR is based on assessment of confirmed complete response (CR) or confirmed partial response (PR). Confirmed CR is defined as disappearance of all target lesions. Confirmed PR is defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response.
Time frame: Baseline up to 6 months after last dose of study treatment, assessed up to 551 days
Population: Response evaluable population included participants who had target lesion or non-target lesion at baseline and received at least 1 study treatment and had at least 1 post-baseline response assessment or discontinued study treatment due to disease progression, or death.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel + Prednisone + Placebo | Number of Participants With Best Overall Response (OR) | Partial Response | 9 Participants |
| Docetaxel + Prednisone + Placebo | Number of Participants With Best Overall Response (OR) | Complete Response | 1 Participants |
| Docetaxel + Prednisone + Intetumumab | Number of Participants With Best Overall Response (OR) | Partial Response | 8 Participants |
| Docetaxel + Prednisone + Intetumumab | Number of Participants With Best Overall Response (OR) | Complete Response | 0 Participants |
p-value: 0.795Fisher Exact
Secondary
Number of Participants With Prostate Specific Antigen (PSA) Response
The PSA response is defined as at least a 50 percent decrease in PSA below the baseline value, confirmed by a second PSA value greater than or equal to 6 weeks later. A participant was considered to be a PSA responder if and only if the response occurs prior to PSA progression (increase of at least 25 percent and an increase of 5 nanogram per milliliter from the lowest observed PSA value since initiation of treatment, to be confirmed greater than or equal to 3 weeks later).
Time frame: Baseline up to 6 months after last dose of study treatment or early withdrawal, assessed up to 601 days
Population: Included all participants randomly assigned to study treatment and had baseline PSA evaluation and at least two post-baseline evaluations that are at least 3 weeks apart.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel + Prednisone + Placebo | Number of Participants With Prostate Specific Antigen (PSA) Response | 43 Participants |
| Docetaxel + Prednisone + Intetumumab | Number of Participants With Prostate Specific Antigen (PSA) Response | 27 Participants |
p-value: 0.018Fisher Exact
Secondary
Overall Survival
Overall Survival is defined as the time from the date of randomization to death due to any cause. For participants who were alive at the time of analysis, overall survival was censored at the last contact date.
Time frame: Baseline until death (up to 887 days)
Population: Efficacy population included all participants randomly assigned to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel + Prednisone + Placebo | Overall Survival | 626.0 Days |
| Docetaxel + Prednisone + Intetumumab | Overall Survival | 522.0 Days |
p-value: 0.16395% CI: [0.853, 2.522]Log Rank
Secondary
Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration
Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.
Time frame: Baseline, Week 6, 7, 10 and 13
Population: The pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study treatment and had at least 1 PD measurement. Here 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 10 (n = 11, 51) | 2.39 Percent change | Standard Deviation 53.537 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 7 (n = 10, 54) | -11.58 Percent change | Standard Deviation 45.396 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 13 (n = 11, 41) | 5.22 Percent change | Standard Deviation 59.728 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 6 (n = 10, 48) | 1.45 Percent change | Standard Deviation 51.019 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 13 (n = 11, 41) | -44.89 Percent change | Standard Deviation 40.941 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 10 (n = 11, 51) | -25.48 Percent change | Standard Deviation 122.178 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 6 (n = 10, 48) | -30.81 Percent change | Standard Deviation 42.091 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent Change at Week 7 (n = 10, 54) | -39.78 Percent change | Standard Deviation 32.437 |
Secondary
Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration
Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.
Time frame: Baseline, Week 6, 7, 10 and 13
Population: The PD analysis set included all participants who received at least 1 dose of study treatment and had at least 1 PD measurement. Here 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 6 (n = 10, 48) | -0.77 Percent change | Standard Deviation 37.584 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 7 (n = 10, 54) | 1.58 Percent change | Standard Deviation 40.651 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 10 (n = 11, 51) | 2.55 Percent change | Standard Deviation 46.433 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 13 (n = 11, 40) | -3.87 Percent change | Standard Deviation 31.845 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 13 (n = 11, 40) | -36.47 Percent change | Standard Deviation 25.701 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 6 (n = 10, 48) | -21.37 Percent change | Standard Deviation 47.747 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 10 (n = 11, 51) | -21.71 Percent change | Standard Deviation 63.89 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent Change at Week 7 (n = 10, 54) | -23.44 Percent change | Standard Deviation 34.703 |
Secondary
Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration
Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.
Time frame: Baseline, Week 6, 7, 10 and 13
Population: The PD analysis set included all participants who received at least 1 dose of study treatment and had at least 1 PD measurement. Here 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 6 (n = 10, 48) | -10.00 Percent change | Standard Deviation 29.609 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 10 (n = 11, 51) | 3.96 Percent change | Standard Deviation 27.859 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 7 (n = 10, 54) | -3.10 Percent change | Standard Deviation 24.465 |
| Docetaxel + Prednisone + Placebo | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 13 (n = 11, 41) | 8.22 Percent change | Standard Deviation 32.622 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 7 (n = 10, 54) | 11.69 Percent change | Standard Deviation 41.338 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 6 (n = 10, 48) | -9.64 Percent change | Standard Deviation 34.229 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 13 (n = 11, 41) | 20.19 Percent change | Standard Deviation 55.565 |
| Docetaxel + Prednisone + Intetumumab | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent Change at Week 10 (n = 11, 51) | 32.11 Percent change | Standard Deviation 85.953 |