Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Gemcitabine (Chemotherapy); Paclitaxel (Chemotherapy); Pertuzumab; Placebo; Topotecan (Chemotherapy)
Intervention description: Participants administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Days 1 and 8 every 3 weeks.; Participants administered paclitaxel at a dosage of 80 mg/m^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.; Participants administered pertuzumab 840 milligrams (mg) 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.; Participants administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.; Participants 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.
Intervention MeSH terms: Paclitaxel; Gemcitabine; Topotecan; Pertuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 208.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        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