Trial Outcomes & Findings for Safety and Efficacy Study of Pertuzumab to Treat Castration-Resistant Prostate Cancer (NCT NCT00058539)

Last Updated: 2015-06-23

Results Overview

Response by tumor measurement occurred if there was documented and confirmed CR or PR. Response was assessed by both the RECIST and by PSA levels measurement, based on measurable or non-measurable disease at baseline. Per RECIST, CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A PSA response was defined as a PSA decline of greater than or equal to (≥) 50%, which had to be confirmed by a second PSA value at least 4 weeks later.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab

Results posted on

2015-06-23

Participant Flow

Participant milestones

Participant milestones
Measure	Pertuzumab All the participants received a loading dose of 840 milligrams (mg) of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an intravenous (IV) infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Overall Study STARTED	42
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Pertuzumab All the participants received a loading dose of 840 milligrams (mg) of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an intravenous (IV) infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Overall Study Disease progression	24
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	5
Overall Study Physician Decision	9
Overall Study Death	1

Baseline Characteristics

Safety and Efficacy Study of Pertuzumab to Treat Castration-Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pertuzumab n=41 Participants All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Age, Continuous	67.7 years STANDARD_DEVIATION 8.8 • n=99 Participants
Sex: Female, Male Female	0 Participants n=99 Participants
Sex: Female, Male Male	41 Participants n=99 Participants

PRIMARY outcome

Timeframe: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab

Population: Efficacy analysis population: All participants who received at least 1 dose of study drug and either underwent at least 1 postbaseline assessment of response or died within 30 days after the last study treatment before any evaluation of response.

Outcome measures

Outcome measures
Measure	Pertuzumab n=30 Participants All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Percentage of Participants With a Best Overall Confirmed Response of Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) and Prostate Specific Antigen (PSA) Response Rate Based on Bubley Criteria	0.0 percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 3 months

Population: Efficacy analysis population.

Outcome measures

Outcome measures
Measure	Pertuzumab n=30 Participants All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Kaplan Meier Estimate of Percentage of Participants With Disease Progression at 3 Months	80 percentage of participants

SECONDARY outcome

Timeframe: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab

Population: Efficacy analysis population. Five participants were censored for this analysis.

PFS was defined as the time from the first day of study drug treatment to the time of documented disease progression or death, whichever came first. Participants who were lost to follow-up or who had not progressed at the time of study completion or early termination were censored at the date of last tumor assessment. The percentage of participants experiencing disease progression or death was calculated as the number of participants with an event divided by the number of participants analyzed, multiplied by 100.

Outcome measures

Outcome measures
Measure	Pertuzumab n=30 Participants All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS])	83.3 percentage of participants

SECONDARY outcome

Timeframe: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab

Population: Efficacy analysis population. Five participants were censored for this analysis.

Outcome measures

Outcome measures
Measure	Pertuzumab n=30 Participants All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Median Time of PFS	9.6 weeks Interval 9.1 to 11.1

SECONDARY outcome

Timeframe: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab

Population: No participants experienced either CR or PR.

Duration of response was defined as the time from the initial CR or PR to the time of disease progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3, 6, and 9 months

Population: Efficacy analysis population

Per RECIST, disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of longest diameter recorded since the treatment started or the appearance of 1 or more new lesions, and/or unequivocal progression of existing non-target lesions. Percentage of participants who were free from disease progression was calculated by subtracting the number of participants with disease progression at that time point from the total population at risk of disease progression, multiplied by 100.

Outcome measures

Outcome measures
Measure	Pertuzumab n=30 Participants All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Percentage of Participants Who Progressed at 3, 6 and 9 Months % of participants progressed at 3 months	66.7 percentage of participants
Percentage of Participants Who Progressed at 3, 6 and 9 Months % of participants progressed at 6 months	80.0 percentage of participants
Percentage of Participants Who Progressed at 3, 6 and 9 Months % of participants progressed at 9 months	83.3 percentage of participants

SECONDARY outcome

Timeframe: Assessed at pre-dose, 15-minutes postdose on Day 1 (Cycle 1), Day 22 (Cycle 2), Day 43 (Cycle 3), Day 85 (Cycle 5), and Day 169 (Cycle 9); pre-dose on Day 253 (Cycle 13), and on Days 8, 15, 29 and 36

Population: Pharmacokinetic evaluable participants

Outcome measures

Outcome measures
Measure	Pertuzumab n=40 Participants All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Serum Concentrations of Pertuzumab Day 1, 15 minutes postdose (n=38)	254.71 micrograms per milliliter (µg/mL) Standard Deviation 46.85
Serum Concentrations of Pertuzumab Day 8 (n=39)	97.51 micrograms per milliliter (µg/mL) Standard Deviation 25.93
Serum Concentrations of Pertuzumab Day 15 (n=38)	69.23 micrograms per milliliter (µg/mL) Standard Deviation 19.13
Serum Concentrations of Pertuzumab Day 22 pre-dose (n=33)	52.41 micrograms per milliliter (µg/mL) Standard Deviation 15.23
Serum Concentrations of Pertuzumab Day 22, 15 minutes postdose (n=31)	175.87 micrograms per milliliter (µg/mL) Standard Deviation 34.70
Serum Concentrations of Pertuzumab Day 29 (n=30)	88.17 micrograms per milliliter (µg/mL) Standard Deviation 27.83
Serum Concentrations of Pertuzumab Day 36 (n=32)	67.45 micrograms per milliliter (µg/mL) Standard Deviation 21.46
Serum Concentrations of Pertuzumab Day 43 pre-dose (n=26)	53.09 micrograms per milliliter (µg/mL) Standard Deviation 19.45
Serum Concentrations of Pertuzumab Day 43, 15 minutes postdose (n=23)	176.17 micrograms per milliliter (µg/mL) Standard Deviation 32.43
Serum Concentrations of Pertuzumab Day 85 pre-dose (n=5)	67.36 micrograms per milliliter (µg/mL) Standard Deviation 23.66
Serum Concentrations of Pertuzumab Day 85, 15 minutes postdose (n=4)	199.50 micrograms per milliliter (µg/mL) Standard Deviation 35.07
Serum Concentrations of Pertuzumab Day 169 pre-dose (n=3)	75.97 micrograms per milliliter (µg/mL) Standard Deviation 49.41
Serum Concentrations of Pertuzumab Day 169, 15 minutes postdose (n=3)	207.67 micrograms per milliliter (µg/mL) Standard Deviation 71.70
Serum Concentrations of Pertuzumab Day 253 pre-dose (n=1)	40.7 micrograms per milliliter (µg/mL) Standard Deviation NA Standard deviation was not analyzed for single participant.

Adverse Events

Pertuzumab

Serious events: 11 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pertuzumab n=41 participants at risk All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Gastrointestinal disorders Constipation	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Gastrointestinal disorders Duodenal ulcer haemorrhage	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Gastrointestinal disorders Ileus	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Renal and urinary disorders Ureteric obstruction	4.9% 2/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Renal and urinary disorders Bilateral hydronephrosis	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Infections and infestations Cellulitis	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Infections and infestations Pneumonia	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Bone pain	4.9% 2/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Cardiac disorders Tachycardia	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
General disorders Pain	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Injury, poisoning and procedural complications Stent occlusion	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Investigations Troponin t increased	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Nervous system disorders Neuropathy	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Vascular disorders Deep vein thrombosis	2.4% 1/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.

Other adverse events

Other adverse events
Measure	Pertuzumab n=41 participants at risk All the participants received a loading dose of 840 mg of pertuzumab on Day 1 of Cycle 1, followed by 420 mg on Day 1 of each subsequent 21-day cycle. Pertuzumab was administered as an IV infusion every 3 weeks for up to 1 year (17 cycles) for participants who showed no evidence of progression. Participants with evidence of disease progression could have continued pertuzumab therapy, at the discretion of the investigator, if they had improvement in pain without an increase in narcotic use and if they had no other therapeutic options.
Gastrointestinal disorders Diarrhoea	61.0% 25/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Gastrointestinal disorders Nausea	34.1% 14/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Gastrointestinal disorders Constipation	19.5% 8/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Gastrointestinal disorders Vomiting	19.5% 8/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Gastrointestinal disorders Abdominal Pain	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Gastrointestinal disorders Stomatitis	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
General disorders Fatigue	34.1% 14/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
General disorders Oedema peripheral	19.5% 8/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
General disorders Mucosal inflammation	14.6% 6/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
General disorders Pain	14.6% 6/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
General disorders Asthenia	12.2% 5/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
General disorders Pyrexia	12.2% 5/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Arthralgia	31.7% 13/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Myalgia	17.1% 7/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Neck pain	12.2% 5/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Back pain	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Chest wall pain	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Pain in extremity	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Musculoskeletal and connective tissue disorders Muscular weakness	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Investigations Ejection fraction decreased	29.3% 12/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Investigations Activated partial thromboplastin time prolonged	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Investigations Prothrombin time prolonged	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Investigations Weight decreased	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Metabolism and nutrition disorders Anorexia	26.8% 11/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Metabolism and nutrition disorders Decreased appetite	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Infections and infestations Upper respiratory tract infection	12.2% 5/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Infections and infestations Urinary tract infection	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Infections and infestations Rhinitis	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Infections and infestations Sinusitis	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.6% 6/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Respiratory, thoracic and mediastinal disorders Cough	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Skin and subcutaneous tissue disorders Rash	17.1% 7/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Skin and subcutaneous tissue disorders Dry skin	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Nervous system disorders Hypoaesthesia	12.2% 5/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Nervous system disorders Dizziness	7.3% 3/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Renal and urinary disorders Dysuria	14.6% 6/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.
Blood and lymphatic system disorders Anaemia	9.8% 4/41 • Adverse events were collected from baseline until up to 30 days after the last dose of pertuzumab.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: : 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER