Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)

• ClinicalTrials.gov Identifier: NCT01684878
• Recruitment Status: Completed
• First Posted: September 13, 2012
• Results First Posted: November 23, 2016
• Last Update Posted: May 23, 2017
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ovarian Cancer
• Interventions: Drug: Gemcitabine (Chemotherapy); Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Placebo; Drug: Topotecan (Chemotherapy)
• Enrollment: 208

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 208 participants were entered into the study, 52 participants in Part 1, and 156 participants in Part 2 of the study. Of these, 203 received treatment with pertuzumab or pertuzumab-placebo (50 participants in Part 1 and 153 participants in Part 2).

Arm/Group Title	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description	Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab-matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Period Title: Part 1: Safety Run in Phase
Started	22	28	0	0
Completed	6	5	0	0
Not Completed	16	23	0	0
Reason Not Completed
Participants withdrawn consent	1	1	0	0
Death	15	20	0	0
Lost to Follow-up	0	2	0	0
Period Title: Part 2: Randomized Phase
Started	0	0	78	78
Participants Randomized But Not Treated	0	0	1	2
Participants Mis-randomized	0	0	2	0
Completed	0	0	0	0
Not Completed	0	0	78	78
Reason Not Completed
Participant withdrew consent	0	0	1	2
Lost to Follow-up	0	0	2	0
Death	0	0	62	68
Alive at data-cut	0	0	13	7
Participant noncompliance	0	0	0	1

Baseline Characteristics

Arm/Group Title		Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy	Total
Arm/Group Description		Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Total of all reporting groups
Overall Number of Baseline Participants		22	28	78	78	206
Baseline Analysis Population Description		Part 1: all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and Part 2: intent-to-treat (ITT) population was defined as all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	22 participants	28 participants	78 participants	78 participants	206 participants
Less than or equal to (≤)65 years		15	17	40	44	116
Greater than (>)65 years		7	11	38	34	90
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	28 participants	78 participants	78 participants	206 participants
	Female	22 100.0%	28 100.0%	78 100.0%	78 100.0%	206 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Part 1: Percentage of Participants With Adverse Events (AEs)
Description	An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)

Outcome Measure Data

Analysis Population Description

All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.

Arm/Group Title	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel
Arm/Group Description:	Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed	22	28
Measure Type: Number; Unit of Measure: percentage of participants
	95.5	100.0

2. Primary Outcome

Title	Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)
Description	PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or 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 treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time Frame	Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Outcome Measure Data

Analysis Population Description

ITT Population was defined as all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).

Arm/Group Title	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description:	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed	78	78
Median (95% Confidence Interval); Unit of Measure: months
	4.27; (3.65 to 6.11)	2.74; (2.14 to 4.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Pertuzumab+Chemotherapy, Part 2: Placebo+Chemotherapy
	Comments	The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan vs paclitaxel), previous anti-angiogenic therapy (yes versus no), and progression-free interval (PFI) since platinum therapy (< 3 months versus 3-6 months). A hazard ratio < 1 favored the pertuzumab + chemotherapy treatment arm.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4983
	Comments	[Not Specified]
	Method	2 sided log-rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (stratified)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.27
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Part 1- Objective Response Rate (ORR)
Description	ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)

Outcome Measure Data

Analysis Population Description

All Treated participants with measurable disease at baseline.

Arm/Group Title	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel
Arm/Group Description:	Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed	14	24
Measure Type: Number; Unit of Measure: percentage of participants
	14.3	25.0

4. Secondary Outcome

Title	Part 2- Objective Response Rate (ORR)
Description	ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Outcome Measure Data

Analysis Population Description

ITT population with measurable disease at baseline.

Arm/Group Title	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description:	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed	61	69
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	14.8; (7.0 to 26.2)	8.7; (3.3 to 18.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Pertuzumab+Chemotherapy, Part 2: Placebo+Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4102
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	6.06
	Confidence Interval	(2-Sided) 95%; 6.0 to 18.3
	Estimation Comments	Approximate 95% CI for difference of 2 rates using Hauck-Anderson method.

5. Secondary Outcome

Title	Part 1: PFS Assessed by the Investigator
Description	PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or 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 treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.
Time Frame	Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)

Outcome Measure Data

Analysis Population Description

All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.

Arm/Group Title	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel
Arm/Group Description:	Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed	22	28
Median (95% Confidence Interval); Unit of Measure: months
	4.07; (1.94 to 6.08)	4.24; (3.45 to 6.01)

6. Secondary Outcome

Title	Part 2: Progression-free Survival (PFS) Assessed by the Investigator
Description	PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or 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 treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time Frame	Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)

Arm/Group Title	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description:	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed	78	78
Median (95% Confidence Interval); Unit of Measure: months
	4.22; (3.25 to 5.22)	3.94; (2.63 to 4.30)

7. Secondary Outcome

Title	Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score
Description	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.
Time Frame	Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).

Arm/Group Title	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description:	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed	78	78
Mean (Standard Deviation); Unit of Measure: units on a scale
Functional Scales: Physical (n=71, 74)	71.1 (22.77)	74.9 (20.85)
Functional Scales: Role (n=70, 73)	68.6 (33.16)	69.4 (32.40)
Functional Scales: Emotional (n=71, 73)	59.5 (24.03)	65.9 (23.42)
Functional Scales: Cognitive (n=71, 73)	81.2 (25.34)	84.9 (20.25)
Functional Scales: Social (n=71, 73)	70.7 (30.01)	68.3 (29.81)
Symptomatic Scales: Fatigue (n=71, 74)	41.2 (28.75)	38.4 (27.77)
Symptomatic Scales: Nausea and vomiting (n=72, 74)	10.4 (15.68)	12.4 (20.47)
Symptomatic Scales: Pain (n=72, 74)	35.2 (31.34)	31.1 (29.24)
Symptomatic Scales: Dyspnoea (n=68, 73)	22.5 (28.47)	21.5 (27.98)
Symptomatic Scales: Insomnia (n=69, 74)	35.3 (31.25)	31.5 (31.16)
Symptomatic Scales: Appetite loss (n=71, 73)	24.9 (30.19)	21.0 (26.36)
Symptomatic Scales: Constipation (n=69, 72)	25.6 (32.41)	26.4 (32.59)
Symptomatic Scales: Diarrhoea (n=69, 72)	14.5 (26.49)	14.4 (22.26)
Symptomatic Scales:Financial difficulties(n=70,72	17.6 (28.78)	13.4 (22.83)
Global health status / QoL scale (n=71, 72)	54.1 (24.99)	61.1 (22.29)

8. Secondary Outcome

Title	Part 2: Percentage of Participants With Adverse Events (AEs)
Description	An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who had received at least 1 dose of pertuzumab, pertuzumab-placebo, or chemotherapy.

Arm/Group Title	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description:	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed	77	76
Measure Type: Number; Unit of Measure: percentage of participants
	98.7	100

9. Secondary Outcome

Title	Part 2: Overall Survival
Description	Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause
Time Frame	Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)

Arm/Group Title	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description:	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed	78	78
Median (95% Confidence Interval); Unit of Measure: months
	10.18; (6.67 to 15.24)	8.36; (6.14 to 11.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Pertuzumab+Chemotherapy, Part 2: Placebo+Chemotherapy
	Comments	The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan versus paclitaxel), previous angiogenic therapy (yes versus no) and PFI since platinum therapy (<3 months versus 3-6 months).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5960
	Comments	[Not Specified]
	Method	2 sided log-rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard ratio (stratified)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.32
	Estimation Comments	A hazard ratio < 1 favored the Pertuzumab + Chemotherapy treatment group

Adverse Events

Time Frame	Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
Arm/Group Description	Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.	Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.	Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
All-Cause Mortality
	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events
	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	9/22 (40.91%)	11/28 (39.29%)	29/77 (37.66%)	33/76 (43.42%)
Blood and lymphatic system disorders
Anaemia † 1	0/22 (0.00%)	2/28 (7.14%)	1/77 (1.30%)	2/76 (2.63%)
Neutropenia † 1	2/22 (9.09%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Febrile Neutropenia † 1	1/22 (4.55%)	0/28 (0.00%)	2/77 (2.60%)	1/76 (1.32%)
Pancytopenia † 1	1/22 (4.55%)	0/28 (0.00%)	2/77 (2.60%)	1/76 (1.32%)
Bone Marrow Failure † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Leukopenia † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Thrombocytopenia † 1	0/22 (0.00%)	0/28 (0.00%)	3/77 (3.90%)	1/76 (1.32%)
Cardiac disorders
Acute Coronary Syndrome † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Acute Myocardial Infarction † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Angina Pectoris † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Cardiac Failure † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Gastrointestinal disorders
Intestinal Obstruction † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	4/76 (5.26%)
Abdominal Pain † 1	1/22 (4.55%)	0/28 (0.00%)	2/77 (2.60%)	2/76 (2.63%)
Diarrhoea † 1	1/22 (4.55%)	0/28 (0.00%)	4/77 (5.19%)	0/76 (0.00%)
Nausea † 1	1/22 (4.55%)	0/28 (0.00%)	1/77 (1.30%)	1/76 (1.32%)
Subileus † 1	1/22 (4.55%)	0/28 (0.00%)	3/77 (3.90%)	1/76 (1.32%)
Vomiting † 1	1/22 (4.55%)	0/28 (0.00%)	3/77 (3.90%)	2/76 (2.63%)
Abdominal Pain Lower † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Abdominal Pain Upper † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Anal Fissure † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Ascites † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	1/76 (1.32%)
Constipation † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Duodenal Fistula † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Ileus † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	2/76 (2.63%)
General disorders
Pyrexia † 1	0/22 (0.00%)	2/28 (7.14%)	1/77 (1.30%)	2/76 (2.63%)
Death † 1	0/22 (0.00%)	1/28 (3.57%)	2/77 (2.60%)	0/76 (0.00%)
Asthenia † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
General Physical Health Deterioration † 1	0/22 (0.00%)	0/28 (0.00%)	2/77 (2.60%)	3/76 (3.95%)
Performance Status Decreased † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Not yet coded † 1 [1]	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Infections and infestations
Abdominal Infection † 1	0/22 (0.00%)	1/28 (3.57%)	1/77 (1.30%)	0/76 (0.00%)
Device Related Infection † 1	0/22 (0.00%)	1/28 (3.57%)	0/77 (0.00%)	0/76 (0.00%)
Peritonitis † 1	1/22 (4.55%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Pyelonephritis † 1	0/22 (0.00%)	1/28 (3.57%)	0/77 (0.00%)	0/76 (0.00%)
Urinary Tract Infection † 1	0/22 (0.00%)	1/28 (3.57%)	1/77 (1.30%)	1/76 (1.32%)
Anal Abscess † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Encephalitis † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Infection † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	1/76 (1.32%)
Infective Myositis † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Kidney Infection † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Meningitis Pneumococcal † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Respiratory Tract Infection † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Sepsis † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	1/76 (1.32%)
Staphylococcal Infection † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Injury, poisoning and procedural complications
Contrast Media Reaction † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Femoral Neck Fracture † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Humerus Fracture † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Investigations
Neutrophil Count Decreased † 1	0/22 (0.00%)	0/28 (0.00%)	2/77 (2.60%)	1/76 (1.32%)
Platelet Count Decreased † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Weight Decreased † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Metabolism and nutrition disorders
Decreased Appetite † 1	1/22 (4.55%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Hypokalaemia † 1	1/22 (4.55%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Dehydration † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian Cancer † 1	0/22 (0.00%)	0/28 (0.00%)	3/77 (3.90%)	2/76 (2.63%)
Nervous system disorders
Cerebral Ischaemia † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Hydrocephalus † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Ischaemic Stroke † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Renal and urinary disorders
Haematuria † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Urinary Tract Disorder † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Urinary Tract Obstruction † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Reproductive system and breast disorders
Vaginal Fistula † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	1/76 (1.32%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	0/22 (0.00%)	1/28 (3.57%)	2/77 (2.60%)	1/76 (1.32%)
Pleural Effusion † 1	1/22 (4.55%)	0/28 (0.00%)	0/77 (0.00%)	2/76 (2.63%)
Skin and subcutaneous tissue disorders
Rash † 1	0/22 (0.00%)	1/28 (3.57%)	0/77 (0.00%)	0/76 (0.00%)
Eczema Asteatotic † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	0/76 (0.00%)
Vascular disorders
Deep Vein Thrombosis † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	2/76 (2.63%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (17.1); [1] This adverse event was not coded at the time of the primary analysis. The preferred term will be reported when available at the final analysis.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part 1: Pertuzumab + Topotecan	Part 1: Pertuzumab + Paclitaxel	Part 2: Pertuzumab+Chemotherapy	Part 2: Placebo+Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	21/22 (95.45%)	27/28 (96.43%)	72/77 (93.51%)	75/76 (98.68%)
Blood and lymphatic system disorders
Anaemia † 1	15/22 (68.18%)	10/28 (35.71%)	28/77 (36.36%)	32/76 (42.11%)
Neutropenia † 1	5/22 (22.73%)	3/28 (10.71%)	23/77 (29.87%)	21/76 (27.63%)
Thrombocytopenia † 1	3/22 (13.64%)	0/28 (0.00%)	3/77 (3.90%)	5/76 (6.58%)
Leukopenia † 1	1/22 (4.55%)	2/28 (7.14%)	4/77 (5.19%)	9/76 (11.84%)
Thrombocytosis † 1	3/22 (13.64%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Febrile Neutropenia † 1	2/22 (9.09%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Eye disorders
Vision Blurred † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	14/22 (63.64%)	22/28 (78.57%)	50/77 (64.94%)	23/76 (30.26%)
Nausea † 1	11/22 (50.00%)	10/28 (35.71%)	31/77 (40.26%)	34/76 (44.74%)
Vomiting † 1	13/22 (59.09%)	5/28 (17.86%)	19/77 (24.68%)	23/76 (30.26%)
Abdominal Pain † 1	6/22 (27.27%)	4/28 (14.29%)	16/77 (20.78%)	21/76 (27.63%)
Constipation † 1	5/22 (22.73%)	5/28 (17.86%)	12/77 (15.58%)	22/76 (28.95%)
Stomatitis † 1	2/22 (9.09%)	5/28 (17.86%)	9/77 (11.69%)	5/76 (6.58%)
Abdominal Pain Upper † 1	3/22 (13.64%)	1/28 (3.57%)	6/77 (7.79%)	9/76 (11.84%)
Dyspepsia † 1	1/22 (4.55%)	3/28 (10.71%)	4/77 (5.19%)	3/76 (3.95%)
Dry Mouth † 1	0/22 (0.00%)	2/28 (7.14%)	2/77 (2.60%)	7/76 (9.21%)
Rectal Haemorrhage † 1	2/22 (9.09%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Abdominal Distension † 1	0/22 (0.00%)	0/28 (0.00%)	4/77 (5.19%)	5/76 (6.58%)
Gastrooesophageal Reflux Disease † 1	0/22 (0.00%)	0/28 (0.00%)	4/77 (5.19%)	1/76 (1.32%)
General disorders
Asthenia † 1	14/22 (63.64%)	8/28 (28.57%)	32/77 (41.56%)	24/76 (31.58%)
Fatigue † 1	5/22 (22.73%)	10/28 (35.71%)	21/77 (27.27%)	24/76 (31.58%)
Pyrexia † 1	5/22 (22.73%)	5/28 (17.86%)	9/77 (11.69%)	12/76 (15.79%)
Mucosal Inflammation † 1	7/22 (31.82%)	2/28 (7.14%)	11/77 (14.29%)	6/76 (7.89%)
Oedema Peripheral † 1	5/22 (22.73%)	2/28 (7.14%)	12/77 (15.58%)	9/76 (11.84%)
Influenza Like Illness † 1	3/22 (13.64%)	0/28 (0.00%)	4/77 (5.19%)	1/76 (1.32%)
Malaise † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Oedema † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Infections and infestations
Nasopharyngitis † 1	2/22 (9.09%)	2/28 (7.14%)	10/77 (12.99%)	6/76 (7.89%)
Urinary Tract Infection † 1	3/22 (13.64%)	1/28 (3.57%)	7/77 (9.09%)	4/76 (5.26%)
Nail Infection † 1	2/22 (9.09%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Upper Respiratory Tract Infection † 1	0/22 (0.00%)	0/28 (0.00%)	4/77 (5.19%)	2/76 (2.63%)
Rhinitis † 1	0/22 (0.00%)	0/28 (0.00%)	4/77 (5.19%)	1/76 (1.32%)
Investigations
Weight Decreased † 1	2/22 (9.09%)	2/28 (7.14%)	2/77 (2.60%)	4/76 (5.26%)
Ejection Fraction Decreased † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Lymphocyte Count Decreased † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Alanine Aminotransferase Increased † 1	0/22 (0.00%)	0/28 (0.00%)	5/77 (6.49%)	6/76 (7.89%)
White Blood Cell Count Decreased † 1	0/22 (0.00%)	0/28 (0.00%)	6/77 (7.79%)	5/76 (6.58%)
Gamma-Glutamyltransferase Increased † 1	0/22 (0.00%)	0/28 (0.00%)	3/77 (3.90%)	7/76 (9.21%)
Neutrophil Count Decreased † 1	0/22 (0.00%)	0/28 (0.00%)	7/77 (9.09%)	2/76 (2.63%)
Aspartate Aminotransferase Increased † 1	0/22 (0.00%)	0/28 (0.00%)	3/77 (3.90%)	5/76 (6.58%)
Blood Alkaline Phosphatase Increased † 1	0/22 (0.00%)	0/28 (0.00%)	3/77 (3.90%)	5/76 (6.58%)
Platelet Count Decreased † 1	0/22 (0.00%)	0/28 (0.00%)	6/77 (7.79%)	2/76 (2.63%)
Blood Creatinine Increased † 1	0/22 (0.00%)	0/28 (0.00%)	1/77 (1.30%)	4/76 (5.26%)
Metabolism and nutrition disorders
Decreased Appetite † 1	8/22 (36.36%)	5/28 (17.86%)	13/77 (16.88%)	17/76 (22.37%)
Hypomagnesaemia † 1	3/22 (13.64%)	4/28 (14.29%)	7/77 (9.09%)	7/76 (9.21%)
Hypokalaemia † 1	1/22 (4.55%)	2/28 (7.14%)	9/77 (11.69%)	5/76 (6.58%)
Hypoalbuminaemia † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Hyponatraemia † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Hypocalcaemia † 1	0/22 (0.00%)	0/28 (0.00%)	4/77 (5.19%)	0/76 (0.00%)
Musculoskeletal and connective tissue disorders
Back Pain † 1	1/22 (4.55%)	6/28 (21.43%)	8/77 (10.39%)	9/76 (11.84%)
Myalgia † 1	1/22 (4.55%)	4/28 (14.29%)	0/77 (0.00%)	0/76 (0.00%)
Arthralgia † 1	0/22 (0.00%)	4/28 (14.29%)	4/77 (5.19%)	5/76 (6.58%)
Muscle Spasms † 1	0/22 (0.00%)	0/28 (0.00%)	6/77 (7.79%)	3/76 (3.95%)
Musculoskeletal Pain † 1	0/22 (0.00%)	0/28 (0.00%)	2/77 (2.60%)	4/76 (5.26%)
Pain In Extremity † 1	0/22 (0.00%)	0/28 (0.00%)	4/77 (5.19%)	2/76 (2.63%)
Nervous system disorders
Peripheral Sensory Neuropathy † 1	2/22 (9.09%)	7/28 (25.00%)	10/77 (12.99%)	9/76 (11.84%)
Headache † 1	3/22 (13.64%)	1/28 (3.57%)	7/77 (9.09%)	5/76 (6.58%)
Dizziness † 1	2/22 (9.09%)	1/28 (3.57%)	7/77 (9.09%)	4/76 (5.26%)
Neuropathy Peripheral † 1	1/22 (4.55%)	2/28 (7.14%)	7/77 (9.09%)	9/76 (11.84%)
Paraesthesia † 1	1/22 (4.55%)	2/28 (7.14%)	4/77 (5.19%)	4/76 (5.26%)
Ageusia † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Dysgeusia † 1	0/22 (0.00%)	2/28 (7.14%)	9/77 (11.69%)	7/76 (9.21%)
Peripheral Motor Neuropathy † 1	0/22 (0.00%)	0/28 (0.00%)	0/77 (0.00%)	4/76 (5.26%)
Psychiatric disorders
Anxiety † 1	0/22 (0.00%)	3/28 (10.71%)	0/77 (0.00%)	0/76 (0.00%)
Insomnia † 1	0/22 (0.00%)	3/28 (10.71%)	5/77 (6.49%)	5/76 (6.58%)
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	5/22 (22.73%)	7/28 (25.00%)	16/77 (20.78%)	5/76 (6.58%)
Cough † 1	5/22 (22.73%)	2/28 (7.14%)	7/77 (9.09%)	5/76 (6.58%)
Dyspnoea † 1	3/22 (13.64%)	4/28 (14.29%)	7/77 (9.09%)	12/76 (15.79%)
Skin and subcutaneous tissue disorders
Alopecia † 1	7/22 (31.82%)	10/28 (35.71%)	15/77 (19.48%)	21/76 (27.63%)
Palmar-Plantar Erythrodysaesthesia Syndrome † 1	0/22 (0.00%)	3/28 (10.71%)	4/77 (5.19%)	0/76 (0.00%)
Nail Disorder † 1	0/22 (0.00%)	3/28 (10.71%)	5/77 (6.49%)	3/76 (3.95%)
Rash † 1	1/22 (4.55%)	2/28 (7.14%)	7/77 (9.09%)	2/76 (2.63%)
Dry Skin † 1	2/22 (9.09%)	0/28 (0.00%)	7/77 (9.09%)	1/76 (1.32%)
Erythema † 1	0/22 (0.00%)	2/28 (7.14%)	0/77 (0.00%)	0/76 (0.00%)
Pain Of Skin † 1	2/22 (9.09%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Rash Maculo-Papular † 1	2/22 (9.09%)	0/28 (0.00%)	0/77 (0.00%)	0/76 (0.00%)
Pruritus † 1	0/22 (0.00%)	0/28 (0.00%)	5/77 (6.49%)	1/76 (1.32%)
Vascular disorders
Hypertension † 1	0/22 (0.00%)	0/28 (0.00%)	4/77 (5.19%)	5/76 (6.58%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (17.1)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lorusso D, Hilpert F, Gonzalez Martin A, Rau J, Ottevanger P, Greimel E, Luck HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastiere-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. doi: 10.1136/ijgc-2019-000370. Epub 2019 Aug 15.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01684878
• Other Study ID Numbers: MO28113; 2011-005975-17 ( EudraCT Number )
• First Submitted: September 11, 2012
• First Posted: September 13, 2012
• Results First Submitted: October 3, 2016
• Results First Posted: November 23, 2016
• Last Update Posted: May 23, 2017