A two-part, randomized Phase II, 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 expressio

Phase 1

• Conditions: Women with recurrent platinum-resistant or refractory epithelial ovarian cancer and low HER3 mRNA expression.; MedDRA version: 14.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005975-17-NL
• Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01-17
• Last Update Posted: 13 June 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 184

Inclusion Criteria

1. Signed written informed consent approved by the relevant IEC/IRB.
2. Female patients aged 18 years or older.
3. Low HER3 mRNA expression levels (concentration ratio equal or lower than 2.81, as assessed by qRT-PCR on a cobas z480 instrument).
4. Histologically or cytologically confirmed and documented epithelial ovarian 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).
5. At least one measurable lesion and/or non measurable disease according to RECIST version 1.1, or cancer antigen-125 (CA-125) assessable disease according to Gynecologic Center Intergroup (GCIG) criteria. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
7. LVEF greater than or equal to 55%.
8. Negative serum pregnancy test in women of childbearing potential (WOCBP; premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization).
9. For WOCBP who are sexually active, agreement to use a highly effective, non hormonal form of contraception or two effective forms of non hormonal contraception during and for at least 6 months post trial treatment (a highly effective non-hormonal form of contraception, such as surgical sterilization, or two effective non-hormonal forms of contraception, such as a barrier method of contraception in conjunction with spermicidal jelly).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64

Exclusion Criteria

1. Non-epithelial tumors.
2. Ovarian tumors with low malignant potential (i.e. borderline tumors).
3. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma, except for 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 breast.
4. 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.
5. 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.
6. Any prior radiotherapy to the pelvis or abdomen.
7. History or evidence on physical/neurological examination of central nervous system disease unrelated to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
8. Pre-exisiting peripheral neuropathy = CTC grade 2.
9. Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count <1,500 cells/mm3.
• Platelet count <100,000 cells/mm3.
• Hemoglobin <9 g/dL.
• Total bilirubin greater than 1.5 ×upper limit of normal (ULN) (unless the patient has documented Gilbert’s syndrome).
• Serum alkaline phosphatase, aspartate aminotransferase (AST; SGOT) or alanine aminotransferase (ALT; SGPT) >2.5 × ULN (or > 5 × ULN in the presence of liver metastases)
• Serum creatinine >2.0 mg/dL or >177 µmol/L.
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).
10. 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) Grade II or higher, or serious cardiac arrhythmia requiring medication.
11. Current known infection with HIV, HBV, or HCV.
12. Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy.
13. 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.
14. Receipt of intravenous antibiotics for infection within 14 days prior to first study drug administration.
15. Current chronic daily treatment with corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids.
16. Known hypersensitivity to any of the trial drugs or excipients.
17. History of receiving any investigational treatment within 28 days prior to first study drug administration, including prior enrollment into Part 1 of the trial.
18. Concurrent participation in any clinical trial.
19. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified