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

Roche

Status and phase: Completed; Phase 3

Conditions: Ovarian Cancer

Treatments: Drug: Topotecan (Chemotherapy); Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Placebo; Drug: Gemcitabine (Chemotherapy)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01684878

MO28113

2011-005975-17 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 208 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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208 participants in 4 patient groups, including a placebo group

Part 1: Pertuzumab + Topotecan

Experimental 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.

Treatment:

Drug: Topotecan (Chemotherapy)

Drug: Paclitaxel (Chemotherapy)

Drug: Pertuzumab

Part 1: Pertuzumab + Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Paclitaxel (Chemotherapy)

Drug: Pertuzumab

Part 2: Pertuzumab+Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Topotecan (Chemotherapy)

Drug: Paclitaxel (Chemotherapy)

Drug: Pertuzumab

Drug: Gemcitabine (Chemotherapy)

Part 2: Placebo+Chemotherapy

Placebo Comparator group

Description:

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.

Treatment:

Drug: Topotecan (Chemotherapy)

Drug: Placebo

Drug: Paclitaxel (Chemotherapy)

Drug: Gemcitabine (Chemotherapy)