Ovarian Cancer MedDRA version: 18.1 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Avelumab
Product Code: MSB0010718C
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Avelumab
Current Sponso
Sponsors
Pfizer Inc, 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer. 2. Platinum-resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum-based therapy (refractory), respectively. 3. Received up to 3 lines of chemotherapy for platinum-sensitive disease, most recently platinum-containing, and no prior therapy for platinum-resistant disease. 4. Measurable disease by investigator assessment with at least 1 unidimensional measurable lesion by RECIST v.1.1 that has not previously been irradiated. 5. At least 18 years of age (=20 years of age in Japan). 6. ECOG performance status (PS) 0 to 1. 7. Estimated life expectancy of at least 3 months. 8. Confirmed availability of archived FFPE tumor tissue block, or a minimum of 15 slides. If archived FFPE tissue is not available, then a de novo (ie, fresh) tumor sample must be obtained in accordance with local institutional practice for tumor biopsies. 9. Adequate bone marrow function, including: a. Absolute neutrophil count (ANC) =1.5 x 10 to the power 9/L; b. Platelet count =100 x 10 to the power 9/L; c. Hemoglobin =9 g/dL (may have been blood transfused). 10. Adequate liver function, including: a. Total bilirubin level =1.5 × the upper limit of normal (ULN). b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x ULN. 11. Adequate renal function as evidenced by: a. Creatinine clearance =50 mL/min as calculated using the Cockcroft-Gault equation. 12. Serum/urine pregnancy test (for females of childbearing potential) negative at screening. 13. Female patients, of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and after the last dose of assigned treatment for the following lengths of time. a. Patients who receive avelumab only: for at least 60 days after the last avelumab dose. b. Patients who receive PLD (alone or in combination with avelumab): for at least 6 months after the last PLD dose. 14. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 15. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. 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 275 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 275
Exclusion criteria
Exclusion criteria: 1. Non-epithelial tumor, including malignant mixed Müllerian tumors without high grade serous component, or ovarian tumors with low malignant potential (ie, borderline tumors). 2. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways). 3. Patients with PLD-resistant EOC, as evidenced by lack of response or progression within 6 months of the last dose of PLD. 4. Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to study entry and are neurologically stable. 5. Concurrent anticancer treatment within 28 days prior to study entry, eg, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy], immunotherapy, or cytokine therapy (except for erythropoietin); major surgery within 28 days prior to study entry (excluding diagnostic biopsy); use of hormonal agents within 7 days prior to study entry; or use of any investigational drug within 28 days prior to study entry. Note: patients receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days prior to study entry. 6. Diagnosis of any other malignancy within 5 years prior to registration, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix. 7. Any one of the following currently or in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation, bradycardia defined as 470 msec at screening (average of triplicate ECG). 9. Left ventricular ejection fraction (LVEF) <50% by MUGA or 2-D echocardiography. 10. Prior anthracycline-related cardiotoxicity or prior anthracycline exposure approaching the lifetime limit. 11. Prior organ transplantation including allogeneic stem-cell transplantation. 12. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. 13. Active infection requiring systemic therapy. 14. Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection. 15. Administration of a live vaccine within 30 days prior to study entry. 16. Current or prior use of immunosuppressive medication within 7 days prior to randomization. The following are exc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): • Overall Survival (OS);Timepoint(s) of evaluation of this end point: As per protocol; Secondary Objective: • To evaluate anti-tumor activity of avelumab given alone or in combination with PLD versus PLD alone in ovarian cancer patients. • To evaluate the overall safety profile of avelumab alone or in combination with PLD versus PLD alone in ovarian cancer patients. • To characterize the PK of doxorubicin (PLD samples) and avelumab when administered in combination, and to assess the effect of avelumab on the PK of doxorubicin (PLD samples) and the effect of PLD on PK of avelumab. • To assess the immunogenicity of avelumab. • To evaluate candidate predictive biomarkers of sensitivity or resistance to avelumab alone or PLD in combination with avelumab in pre-treatment tumor tissue, that may aid in the identification of patient subpopulations most likely to benefit from treatment. • To compare the effect of avelumab alone or in combination with PLD versus PLD alone on patient-reported outcomes (PRO) in patients with ovarian cancer. ; Main Objective: • To demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging OS in patients with platinum -resistant/platinum-refractory ovarian cancer. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Efficacy: Objective response (OR), Progression-Free Survival (PFS), Duration of Response (DR), and Disease Control (DC) as determined by Blinded Independent Central Review (BICR) and Investigator [As assessed by RECIST version 1.1]. • Safety: AEs (as graded by NCI CTCAE v.4.03); laboratory abnormalities (as graded by NCI CTCAE v.4.03); vital signs (blood pressure, pulse rate); electrocardiograms (ECGs), ECHO or MUGA scans. • Pharmacokinetics: PK parameters, including Ctrough for avelumab, Cmax, volume of distribution (Vd), clearance (CL), area under the concentration-time curve (AUC) for doxorubicin (PLD samples). • Immunogenicity: Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nab) against avelumab. • Candidate predictive biomarkers in tumor tissue including, but not limited to, PD-L1 expression and tumor infiltrating CD8+ T lymphocytes as assessed by immunohistochemistry (IHC). • Patient-Reported Outcomes: EORTC QLQ-C30, EORTC QLQ-OV28, and EuroQol5 Dimension (EQ-5D). ;Timepoint(s) of evaluation of this end point: As per protocol | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc
Outcome results
None listed