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

Ovarian Cancer Clinical Trial

Official title:

A Two-Part, Randomized Phase III, Double-Blind, Multicenter Trial Assessing The Efficacy And Safety of Pertuzumab In Combination With Standard Chemotherapy Vs. Placebo Plus Standard Chemotherapy In Women With Recurrent Platinum-Resistant Epithelial Ovarian Cancer And Low HER3 mRNA Expression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01684878
• Other study ID #: MO28113
• Secondary ID: 2011-005975-17
• Status: Completed
• Phase: Phase 3
• First received: September 11, 2012
• Last updated: July 5, 2016
• Start date: October 2012
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Health Authority Spain
• Study type: Interventional

Clinical Trial Summary

This two-part, multicenter study will evaluate the safety, tolerability and efficacy of pertuzumab in combination with standard chemotherapy in women with recurrent platinum-resistant epithelial ovarian cancer. In the non-randomized Part 1 safety run-in, participants will receive pertuzumab plus either topotecan or paclitaxel. In the randomized, double-blind Part 2 of the study, participants will receive either pertuzumab or placebo in combination with chemotherapy (topotecan, paclitaxel, or gemcitabine).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed epithelial ovarian, primary peritoneal, and/or fallopian tube cancer that is platinum-resistant or refractory

• Low Human epidermal growth factor receptor (HER) 3 messenger ribonucleic acid (mRNA) expression

• At least one measurable and/or non-measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

• Left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 50 percent (%)

• Negative serum pregnancy test in women of childbearing potential

• Women of childbearing potential must agree to use effective contraception as defined by protocol during and for at least 6 months post study treatment

Exclusion Criteria:

• Non-epithelial tumors

• Ovarian tumors with low malignant potential (borderline tumors)

• History of other malignancy of prognostic relevance within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma, or tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the breast

• Previous treatment with more than 2 chemotherapy regimens

• Any prior radiotherapy to the pelvis or abdomen

• History or evidence on physical/neurological examination of central nervous system disease unrelated to cancer (uncontrolled seizures), unless adequately treated with standard medical therapy

• Pre-existing peripheral neuropathy >/= common toxicity criteria (CTC) grade 2 (applicable for paclitaxel cohort only)

• Inadequate organ function

• Uncontrolled hypertension or clinically significant cardiovascular disease

• Current known infection with human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV), or hepatitis C virus (HCV)

• Current chronic daily treatment with corticosteroids (>/= 10 mg per day of methylprednisolone or equivalent), excluding inhaled steroids

• History of receiving any investigational treatment within 28 days prior to first study drug administration

• For Part 2 of the trial: prior enrollment into Part 1 of the trial

• Concurrent participation in any therapeutic clinical trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Gemcitabine (Chemotherapy)
Participants will be administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m^2) IV infusion on Days 1 and 8 every 3 weeks.
• Paclitaxel (Chemotherapy)
Participants will be administered paclitaxel at a dosage of 80 milligrams per meter square (mg/m^2) as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.
• Pertuzumab
Participants will be administered pertuzumab 840 milligrams (mg) intravenous (IV) infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.
• Placebo
Participants will be administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.
• Topotecan (Chemotherapy)
Participants will be administered topotecan at a dosage of 1.25 mg/m^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  France,  Germany,  Italy,  Netherlands,  Norway,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of Participants with Adverse Events		Approximately 3.5 years (assessed at screening, baseline until 28 days after the last dose of study treatment)	No
Primary	Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Using Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.1		Approximately 3.5 years (assessed at screening and every 9 weeks from randomization until disease progression)	No
Secondary	QoL Assessment Using EORCTC QLQ-Ovarian Cancer Module (OV) 28 Score		Approximately 3.5 years (assessed at baseline and every 9 weeks from randomization until disease progression)	No
Secondary	Functional Assessment of Cancer Therapy (FACT)/National Comprehensive Cancer Network (NCCN) Ovarian Symptom Index (FOSI) Total Score		Approximately 3.5 years (assessed at baseline and every 9 weeks from randomization until disease progression)	No
Secondary	QoL Assessment Using Three Worst Symptoms Questionnaires Score		Baseline	No
Secondary	Part 2: Progression-free survival Assessed by the Investigator using RECIST V1.1		Approximately 3.5 years (assessed at screening and every 9 weeks from randomization until disease progression)	No
Secondary	QoL Assessment Using Hospital Anxiety Depression Scale (HADS) Score		Approximately 3.5 years (assessed at baseline and every 9 weeks from randomization until disease progression)	No
Secondary	Part 1: PFS Assessed by the Investigator Using RECIST V1.1		Approximately 3.5 years (assessed at screening and every 9 weeks from randomization until disease progression)	No
Secondary	Part 2: Overall Survival		Approximately 3.5 years (assessed at screening, baseline, 28 days after the last dose of study treatment, 3 months post treatment follow-up)	No
Secondary	Part 2: Percentage of Participants with an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST V 1.1		Approximately 3.5 years (assessed at screening and every 9 weeks from randomization until disease progression)	No
Secondary	Part 2: Percentage of Participants with Adverse Events		Approximately 3.5 years (assessed at screening, baseline until 28 days after the last dose of study treatment)	No
Secondary	Part 2: Quality of Life (QoL) - European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ) of Core 30 (C30) Score		Approximately 3.5 years (assessed at baseline and every 9 weeks from randomization until disease progression)	No