A two-part randomized phase III double blind muticenter 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

STUDIE IS GESLOTEN

Randomisation between:

 Inclusion criteria

  • Signed written informed consent approved by the relevant IEC
  • Female patients aged 18 years or older.
  • Low HER3 mRNA expression levels (concentration ratio equal or lower than 2.81, as assessed by qRT-PCR on a cobas z480 instrument in a local central laboratory). 
  • Histologically or cytologically confirmed and documented epithelial ovarian, primary peritoneal, and/or fallopian tube cancer that is platinum-resistant or refractory (defined as progression within 6 months from completion of a minimum of 4 platinum therapy cycles or progression during platinum therapy).
  • At least one measurable lesion and/or non-measurable lesion according to RECIST version 1.1. The following histological types are eligible:
    • Adenocarcinoma not otherwise specified.
    • Clear cell adenocarcinoma.
    • Endometrioid adenocarcinoma.
    • Malignant Brenner's tumor.
    • Mixed epithelial carcinoma including malignant mixed Müllerian tumors.
    • Mucinous adenocarcinoma.
    • Serous adenocarcinoma.
    • Transitional cell carcinoma.
    • Undifferentiated carcinoma 
  • ECOG performance status 0 to 2
  • LVEF greater than or equal to 50% 

Exclusion criteria

  • Non-epithelial tumor
  • Ovarian tumors with low malignant potential (i.e. 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, 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 breast
  • Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or that would put the patient at high risk for treatment-related complications
  • Previous treatment with more than 2 chemotherapy regimens, . If a patient has previously been treated with topotecan, paclitaxel, or gemcitabine as second-line therapy, the patient will not be retreated with the same agent
  • Any prior radiotherapy to the pelvis or abdomen
  • History or evidence on physical/neurological examination of central nervous system disease unrelated to cancer(e.g. uncontrolled seizures), unless adequately treated with standard medical therapy
  • Preexisiting peripheral neuropathy ≥ CTC grade 2(applicable for the paclitaxel cohort only)
  • Inadequate organ function by lab tests
  • Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA)any grade or uncontrollable high risk cardiac arrhythmia(i.e. atrial tachycardia with a heart rate>100/min at rest) or higher grade atroiventricular (AV) block(second degree AC block Type 2[Mobitz 2]or third degree AV block
  • Current known infection with HIV or active infection with, HBV, or HCV
  • Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
  • Major surgical procedure or significant traumatic injury within 28 days prior to first study drug administration or anticipation of need for major surgery during the course of study treatment
  • Receipt of i.v. antibiotics for infection within 7 days prior to first study drug administration
  • Current chronic daily treatment with corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids
  • Known hypersensitivity to any of the trial drugs or excipients.

 Deelnemende centra: Antoni van Leeuwenhoek, LUMC, UMCG en Radboud MC