Trial Outcomes & Findings for A Study of the Safety and Efficacy of Single-agent Carlumab (an Anti-Chemokine Ligand 2 [CCL2]) in Participants With Metastatic Castrate-Resistant Prostate Cancer (NCT NCT00992186)

Last Updated: 2013-06-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

Up to 4 weeks before first dose, every 12 weeks after first dose, Week 12 after last dose of carlumab

Results posted on

2013-06-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	46
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	46

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Withdrawal by Subject	2
Overall Study Protocol Violation	1
Overall Study Physician Decision	1
Overall Study Adverse Event	9
Overall Study Progressive Disease	30
Overall Study Refusal To Receive Study Agent	3

Baseline Characteristics

A Study of the Safety and Efficacy of Single-agent Carlumab (an Anti-Chemokine Ligand 2 [CCL2]) in Participants With Metastatic Castrate-Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carlumab n=46 Participants 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.
Age Continuous	67.5 Years STANDARD_DEVIATION 7.95 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants
Region of Enrollment Belgium	11 participants n=5 Participants
Region of Enrollment Russian Federation	10 participants n=5 Participants
Region of Enrollment United Kingdom	18 participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Carlumab n=41 Participants 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.
Percentage of Participants With Composite Response CR or PR	0.0 Percentage of participants
Percentage of Participants With Composite Response PSA response	0.0 Percentage of participants
Percentage of Participants With Composite Response Stable disease	2.4 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Carlumab n=41 Participants 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.
Percentage of Participants With Objective Tumor Response CR	0.0 Percentage of participants
Percentage of Participants With Objective Tumor Response PR	0.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Carlumab n=46 Participants 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.
Progression-Free Survival (PFS)	81.0 Days Interval 76.0 to 85.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Carlumab n=46 Participants 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.
Overall Survival (OS)	309.0 Days Interval 47.0 to 582.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Carlumab n=44 Participants 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.
Percentage of Participants With Prostate Specific Antigen (PSA) Response	0.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Carlumab n=7 Participants 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.
Percentage of Participants With Urinary Crosslinked N-Telopeptide of Type I Collagen (NTx) Response	0.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Carlumab n=31 Participants 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.
Percentage of Participants With Pain Response During stable use of analgesic medication	32.3 Percentage of participants
Percentage of Participants With Pain Response At any time	38.7 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Carlumab n=35 Participants 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.
Minimum Observed Serum Concentration (Cmin)	91.82 microgram/milliliter (mcg/mL) Standard Deviation 87.240

SECONDARY outcome

Timeframe: 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.

The maximum observed analyte concentration was measured.

Outcome measures

Outcome measures
Measure	Carlumab n=46 Participants 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.
Maximum Observed Serum Concentration (Cmax)	320.27 mcg/mL Standard Deviation 75.712

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Carlumab n=41 Participants 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.
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 outcome

Timeframe: 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.

The time measured for the serum concentration to decrease by one half.

Outcome measures

Outcome measures
Measure	Carlumab n=7 Participants 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.
Half-life (t1/2)	13.32 Days Interval 8.7 to 20.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Carlumab n=46 Participants 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.
Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Status Score	86.0 Days Interval 56.0 to 176.0

Adverse Events

Carlumab

Serious events: 20 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Carlumab n=46 participants at risk 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.
General disorders General physical health deterioration	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
General disorders Multi-organ failure	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
General disorders Oedema peripheral	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
General disorders Pain	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
General disorders Pyrexia	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Back pain	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Bone pain	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to stomach	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Nervous system disorders Spinal cord compression	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Nervous system disorders Nerve root compression	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Abdominal pain	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Constipation	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Gastric perforation	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Gastrointestinal perforation	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Infections and infestations Pneumonia	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Respiratory, thoracic and mediastinal disorders Epistaxis	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Eye disorders Vitreous detachment	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Psychiatric disorders Confusional state	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Renal and urinary disorders Haematuria	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab
Renal and urinary disorders Urinary tract obstruction	2.2% 1/46 • Baseline up to 30 days after last dose of carlumab

Other adverse events

Other adverse events
Measure	Carlumab n=46 participants at risk 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.
Musculoskeletal and connective tissue disorders Back pain	32.6% 15/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Bone pain	19.6% 9/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Arthralgia	13.0% 6/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.0% 6/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Groin pain	10.9% 5/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Pain in extremity	10.9% 5/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Muscular weakness	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
General disorders Fatigue	52.2% 24/46 • Baseline up to 30 days after last dose of carlumab
General disorders Oedema peripheral	13.0% 6/46 • Baseline up to 30 days after last dose of carlumab
General disorders Asthenia	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Diarrhoea	17.4% 8/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Nausea	17.4% 8/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Constipation	15.2% 7/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Vomiting	10.9% 5/46 • Baseline up to 30 days after last dose of carlumab
Gastrointestinal disorders Abdominal pain upper	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Blood and lymphatic system disorders Anaemia	26.1% 12/46 • Baseline up to 30 days after last dose of carlumab
Blood and lymphatic system disorders Thrombocytopenia	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
Metabolism and nutrition disorders Decreased appetite	23.9% 11/46 • Baseline up to 30 days after last dose of carlumab
Metabolism and nutrition disorders Dehydration	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Nervous system disorders Dizziness	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
Nervous system disorders Headache	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
Psychiatric disorders Confusional state	10.9% 5/46 • Baseline up to 30 days after last dose of carlumab
Psychiatric disorders Insomnia	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
Respiratory, thoracic and mediastinal disorders Cough	13.0% 6/46 • Baseline up to 30 days after last dose of carlumab
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Skin and subcutaneous tissue disorders Pruritus	8.7% 4/46 • Baseline up to 30 days after last dose of carlumab
Infections and infestations Gastroenteritis	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Investigations Weight decreased	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab
Vascular disorders Hypertension	6.5% 3/46 • Baseline up to 30 days after last dose of carlumab

Additional Information

Senior Director, Early Clinical Development Global Leader

Centocor Research & Development, Inc., PA, USA

Phone: +1-908-927-3159

Results disclosure agreements

Principal investigator is a sponsor employee If Investigator wishes to publish information from study, a copy of manuscript must be provided to Sponsor for review at least 60 days before publication. Expedited reviews will be arranged for abstracts, poster presentations. If requested by Sponsor in writing, Investigator will withhold such publication for up to additional 60 days to allow for patent filing. If the issues arise regarding scientific integrity or regulatory compliance, Sponsor will review them with Investigator.
Publication restrictions are in place

Restriction type: OTHER