Trial Outcomes & Findings for A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian Cancer (NCT NCT00058552)

NCT ID: NCT00058552

Last Updated: 2017-03-08

Results Overview

Response by tumor measurement occurred if there was documented and confirmed CR or PR determined by 2 consecutive investigator assessments that were at least 28 days apart. Response was assessed by either the RECIST v 1.1 or by CA-125 changes, based on measurable or non-measurable disease at baseline. Per RECIST v 1.1 (for measurable disease), 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 longest diameter. Per CA-125 changes (for non-measurable disease), CR: decrease in the CA-125 to within the normal limits and less than (\<) 40 international units per milliliter (IU/mL) and no clinical or radiological evidence of disease, PR: a greater than (\>) 50 percent (%) decrease in CA-125 values from baseline, and no clinical or radiological evidence of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

129 participants

Primary outcome timeframe

Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)

Results posted on

2017-03-08

Participant Flow

Participant milestones

Participant milestones
Measure
Pertuzumab 420 mg
Participants in this group received pertuzumab intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for Cycle 1 (1 Cycle equals to \[=\] 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Overall Study
STARTED
65
64
Overall Study
COMPLETED
0
2
Overall Study
NOT COMPLETED
65
62

Reasons for withdrawal

Reasons for withdrawal
Measure
Pertuzumab 420 mg
Participants in this group received pertuzumab intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for Cycle 1 (1 Cycle equals to \[=\] 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Overall Study
Died prior to receiving treatment
4
2
Overall Study
Disease progression
52
44
Overall Study
Adverse Event
4
2
Overall Study
Withdrawal by Subject
3
5
Overall Study
Physician Decision
2
5
Overall Study
Clinical disease progression
0
4

Baseline Characteristics

A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Pertuzumab 420 mg
n=61 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Total
n=123 Participants
Total of all reporting groups
Age, Continuous
58.1 years
STANDARD_DEVIATION 9.9 • n=99 Participants
56.5 years
STANDARD_DEVIATION 11.2 • n=107 Participants
57.3 years
STANDARD_DEVIATION 10.5 • n=206 Participants
Sex: Female, Male
Female
61 Participants
n=99 Participants
62 Participants
n=107 Participants
123 Participants
n=206 Participants
Sex: Female, Male
Male
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants

PRIMARY outcome

Timeframe: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (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 one postbaseline assessment of response or died within 30 days after the last study treatment before any evaluation of response.

Response by tumor measurement occurred if there was documented and confirmed CR or PR determined by 2 consecutive investigator assessments that were at least 28 days apart. Response was assessed by either the RECIST v 1.1 or by CA-125 changes, based on measurable or non-measurable disease at baseline. Per RECIST v 1.1 (for measurable disease), 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 longest diameter. Per CA-125 changes (for non-measurable disease), CR: decrease in the CA-125 to within the normal limits and less than (\<) 40 international units per milliliter (IU/mL) and no clinical or radiological evidence of disease, PR: a greater than (\>) 50 percent (%) decrease in CA-125 values from baseline, and no clinical or radiological evidence of new lesions.

Outcome measures

Outcome measures
Measure
Pertuzumab 420 mg
n=55 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes
3.6 percentage of participants
Interval 0.7 to 11.8
4.8 percentage of participants
Interval 1.3 to 12.9

SECONDARY outcome

Timeframe: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)

Population: Efficacy Analysis Population. Six participants in pertuzumab 420 mg treatment arm and 15 participants in pertuzumab 1050 mg treatment arm 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 event divided by the number of participants analyzed, multiplied by 100.

Outcome measures

Outcome measures
Measure
Pertuzumab 420 mg
n=55 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS])
89.1 percentage of participants
75.8 percentage of participants

SECONDARY outcome

Timeframe: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)

Population: Efficacy Analysis Population. Six participants in pertuzumab 420 mg treatment arm and 15 participants in pertuzumab 1050 mg treatment arm 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.

Outcome measures

Outcome measures
Measure
Pertuzumab 420 mg
n=55 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Median Time of PFS
7.6 weeks
Interval 6.0 to 11.4
6.1 weeks
Interval 5.9 to 11.4

SECONDARY outcome

Timeframe: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)

Population: Only responders (CR or PR) were included in the analysis.

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

Outcome measures

Outcome measures
Measure
Pertuzumab 420 mg
n=2 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=3 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Duration of Response
18.6 weeks
Interval 17.9 to 19.4
21.1 weeks
Interval 13.1 to 29.1

SECONDARY outcome

Timeframe: Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years)

Population: Efficacy Analysis Population.

The percentage of participants experiencing death was calculated as the number of participants with event divided by the number of participants analyzed, multiplied by 100.

Outcome measures

Outcome measures
Measure
Pertuzumab 420 mg
n=55 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Percentage of Participants Who Died
69.1 percentage of participants
46.8 percentage of participants

SECONDARY outcome

Timeframe: Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years)

Population: Efficacy Analysis Population. Seventeen participants in pertuzumab 420 mg arm and 33 participants in pertuzumab 1050 mg were censored for this analysis.

Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive.

Outcome measures

Outcome measures
Measure
Pertuzumab 420 mg
n=55 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Overall Survival
46.7 weeks
Interval 30.4 to 66.6
NA weeks
Interval 38.9 to
Data for 33 participants were censored, thus median and confidence interval upper limit were not reached.

SECONDARY outcome

Timeframe: 3, 6, and 12 months

Population: Efficacy Analysis Population.

Per RECIST v 1.1, 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 longest diameter recorded since the treatment started or the appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure
Pertuzumab 420 mg
n=55 Participants
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 Participants
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months
% of participants free from PD at 3 months
25.5 percentage of participants
24.2 percentage of participants
Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months
% of participants free from PD at 6 months
7.3 percentage of participants
6.5 percentage of participants
Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months
% of participants free from PD at 12 months
0.0 percentage of participants
0.0 percentage of participants

Adverse Events

Pertuzumab 420 mg

Serious events: 26 serious events
Other events: 61 other events
Deaths: 0 deaths

Pertuzumab 1050 mg

Serious events: 18 serious events
Other events: 60 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Pertuzumab 420 mg
n=61 participants at risk
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 participants at risk
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Gastrointestinal disorders
Small intestinal obstruction
13.1%
8/61
9.7%
6/62
Gastrointestinal disorders
Intestinal obstruction
3.3%
2/61
3.2%
2/62
Gastrointestinal disorders
Abdomial pain
3.3%
2/61
1.6%
1/62
Gastrointestinal disorders
Ascites
3.3%
2/61
0.00%
0/62
Gastrointestinal disorders
Diarrhoea
3.3%
2/61
0.00%
0/62
Gastrointestinal disorders
Vomiting
3.3%
2/61
0.00%
0/62
Gastrointestinal disorders
Nausea
1.6%
1/61
0.00%
0/62
Respiratory, thoracic and mediastinal disorders
Pleural effusion
1.6%
1/61
3.2%
2/62
Respiratory, thoracic and mediastinal disorders
Aspiration
3.3%
2/61
0.00%
0/62
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.00%
0/61
1.6%
1/62
Renal and urinary disorders
Bladder pain
0.00%
0/61
1.6%
1/62
Renal and urinary disorders
Bladder spasm
0.00%
0/61
1.6%
1/62
Renal and urinary disorders
Obstructive uropathy
1.6%
1/61
0.00%
0/62
Renal and urinary disorders
Renal failure acute
0.00%
0/61
1.6%
1/62
Renal and urinary disorders
Ureteric obstruction
0.00%
0/61
1.6%
1/62
Cardiac disorders
Atrial fibrillation
1.6%
1/61
0.00%
0/62
Cardiac disorders
Cardiac tamponade
0.00%
0/61
1.6%
1/62
Cardiac disorders
Endocarditis noninfective
1.6%
1/61
0.00%
0/62
Cardiac disorders
Pericardial effusion
0.00%
0/61
1.6%
1/62
Metabolism and nutrition disorders
Dehydration
1.6%
1/61
3.2%
2/62
Metabolism and nutrition disorders
Hypercalcaemia
0.00%
0/61
1.6%
1/62
Infections and infestations
Abdominal abscess
1.6%
1/61
0.00%
0/62
Infections and infestations
Influenza
1.6%
1/61
0.00%
0/62
Infections and infestations
Pneumonia
1.6%
1/61
0.00%
0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant ascites
1.6%
1/61
0.00%
0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
1.6%
1/61
0.00%
0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer
0.00%
0/61
1.6%
1/62
General disorders
Asthenia
1.6%
1/61
0.00%
0/62
Hepatobiliary disorders
Hepatic function abnormal
1.6%
1/61
0.00%
0/62
Injury, poisoning and procedural complications
Intestinal stoma complication
1.6%
1/61
0.00%
0/62
Investigations
Ejection fraction decreased
0.00%
0/61
1.6%
1/62
Vascular disorders
Thrombosis
1.6%
1/61
0.00%
0/62

Other adverse events

Other adverse events
Measure
Pertuzumab 420 mg
n=61 participants at risk
Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression.
Pertuzumab 1050 mg
n=62 participants at risk
Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression.
Skin and subcutaneous tissue disorders
Pruritis
13.1%
8/61
11.3%
7/62
Skin and subcutaneous tissue disorders
Dry skin
8.2%
5/61
11.3%
7/62
Skin and subcutaneous tissue disorders
Erythema
6.6%
4/61
9.7%
6/62
Skin and subcutaneous tissue disorders
Rash erythematous
3.3%
2/61
6.5%
4/62
Skin and subcutaneous tissue disorders
Nail disorder
6.6%
4/61
1.6%
1/62
Investigations
Ejection fraction decreased
18.0%
11/61
21.0%
13/62
Investigations
Weight decreased
16.4%
10/61
14.5%
9/62
Investigations
Haemoglobin decreased
9.8%
6/61
6.5%
4/62
Respiratory, thoracic and mediastinal disorders
Cough
14.8%
9/61
17.7%
11/62
Respiratory, thoracic and mediastinal disorders
Dyspnoea
16.4%
10/61
16.1%
10/62
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
4.9%
3/61
8.1%
5/62
Respiratory, thoracic and mediastinal disorders
Pleural effusion
9.8%
6/61
3.2%
2/62
Respiratory, thoracic and mediastinal disorders
Epistaxis
4.9%
3/61
6.5%
4/62
Respiratory, thoracic and mediastinal disorders
Nasal congestion
6.6%
4/61
1.6%
1/62
Nervous system disorders
Headache
16.4%
10/61
9.7%
6/62
Nervous system disorders
Dizziness
11.5%
7/61
9.7%
6/62
Nervous system disorders
Dysgeusia
6.6%
4/61
3.2%
2/62
Nervous system disorders
Paraesthesia
6.6%
4/61
3.2%
2/62
Nervous system disorders
Hypoaesthesia
0.00%
0/61
6.5%
4/62
Musculoskeletal and connective tissue disorders
Back pain
13.1%
8/61
6.5%
4/62
Musculoskeletal and connective tissue disorders
Arthralgia
4.9%
3/61
11.3%
7/62
Musculoskeletal and connective tissue disorders
Muscle spasms
0.00%
0/61
14.5%
9/62
Musculoskeletal and connective tissue disorders
Myalgia
6.6%
4/61
3.2%
2/62
Infections and infestations
Urinary tract infection
9.8%
6/61
12.9%
8/62
Infections and infestations
Sinusitis
6.6%
4/61
6.5%
4/62
Gastrointestinal disorders
Diarrhoea
65.6%
40/61
72.6%
45/62
Gastrointestinal disorders
Abdominal pain
41.0%
25/61
32.3%
20/62
Gastrointestinal disorders
Nausea
36.1%
22/61
35.5%
22/62
Gastrointestinal disorders
Vomiting
36.1%
22/61
27.4%
17/62
Gastrointestinal disorders
Constipation
27.9%
17/61
17.7%
11/62
Gastrointestinal disorders
Abdominal distention
21.3%
13/61
12.9%
8/62
Gastrointestinal disorders
Dyspepsia
9.8%
6/61
21.0%
13/62
Gastrointestinal disorders
Stomatitis
6.6%
4/61
12.9%
8/62
Gastrointestinal disorders
Abdominal pain upper
11.5%
7/61
6.5%
4/62
Gastrointestinal disorders
Ascites
8.2%
5/61
4.8%
3/62
Gastrointestinal disorders
Abdominal discomfort
3.3%
2/61
8.1%
5/62
Gastrointestinal disorders
Haematochezia
6.6%
4/61
3.2%
2/62
General disorders
Fatigue
34.4%
21/61
53.2%
33/62
General disorders
Odema peripheral
21.3%
13/61
22.6%
14/62
General disorders
Pyrexia
11.5%
7/61
6.5%
4/62
General disorders
Asthenia
13.1%
8/61
3.2%
2/62
General disorders
Pain
8.2%
5/61
4.8%
3/62
General disorders
Chills
6.6%
4/61
4.8%
3/62
General disorders
Early satiety
3.3%
2/61
6.5%
4/62
General disorders
Oedema
6.6%
4/61
1.6%
1/62
General disorders
Mucosal inflammation
6.6%
4/61
0.00%
0/62
Metabolism and nutrition disorders
Anorexia
24.6%
15/61
19.4%
12/62
Metabolism and nutrition disorders
Dehydration
19.7%
12/61
11.3%
7/62
Metabolism and nutrition disorders
Hypokalaemia
9.8%
6/61
14.5%
9/62
Metabolism and nutrition disorders
Hypoalbuminaemia
8.2%
5/61
8.1%
5/62
Metabolism and nutrition disorders
Decreased appetite
8.2%
5/61
4.8%
3/62
Skin and subcutaneous tissue disorders
Rash
23.0%
14/61
25.8%
16/62
Infections and infestations
Upper respiratory tract infection
6.6%
4/61
4.8%
3/62
Infections and infestations
Rhinitis
8.2%
5/61
1.6%
1/62
Psychiatric disorders
Insomnia
16.4%
10/61
8.1%
5/62
Psychiatric disorders
Anxiety
9.8%
6/61
8.1%
5/62
Psychiatric disorders
Depression
9.8%
6/61
3.2%
2/62
Blood and lymphatic system disorders
Anaemia
14.8%
9/61
16.1%
10/62
Renal and urinary disorders
Dysuria
11.5%
7/61
9.7%
6/62
Renal and urinary disorders
Haematuria
8.2%
5/61
3.2%
2/62
Cardiac disorders
Tachycardia
8.2%
5/61
3.2%
2/62

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

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