Epithelial ovarian cancer (EOC) MedDRA version: 20.0 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: Concentrate for solution for infusion
INN or Proposed INN: Avelumab
Other descriptive name: MSB0010718C
Concentration unit: mg/ml
Sponsors
Pfizer Inc, 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (according to AJCC/UICC TNM and International Federation of Gynecology and Obstetrics (FIGO) Staging System 2014 edition), including malignant mixed Müllerian tumors with high grade serous component. 2. Patients must be candidates for platinum-based chemotherapy and previously untreated. 3. Patients must have completed a surgical debulking procedure, or be candidates for neoadjuvant chemotherapy. a. For patients enrolling after debulking surgery, the following conditions must be met: • The minimum surgery required is an abdominal surgery with an attempt at cytoreduction providing tissue for histologic evaluation and establishing and documenting the primary site and stage • Patient must be randomized at a maximum of 8 weeks after surgery. b. For patients who are candidates for neoadjuvant chemotherapy, the following conditions must be met: • A core tissue (not fine needle aspiration) biopsy is required. The tissue must be consistent with a tumor of Müllerian origin. • Stage IIIC–IV documented via imaging or surgery (without attempt at cytoreduction) • Serum CA125/ CEA ratio > 25. If the serum CA125/CEA ratio is < 25, workup should be negative for the presence of a primary gastrointestinal or breast malignancy (< 6 weeks before randomization). • Plan to receive carboplatin-paclitaxel neoadjuvant chemotherapy. • Randomization must occur within 8 weeks after diagnosis. 4. Availability of an archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or a minimum of 15 slides. If archived FFPE tissue is not available, a de novo (ie, fresh) tumor sample must be obtained in accordance with local institutional practice for tumor biopsies. 5. Eastern Cooperative Group (ECOG) performance status 0-1 6. Age =18 years (or =20 years in Japan). 7. Adequate hematological function (ANC =1.5 x 10 to the power 9/L, Hgb =9.0 g/dL, and platelet count =100 x 10 to the power 9/L). 8. Adequate liver function tests (ALT/AST =2.5 x ULN, total serum bilirubin level =1.5 x ULN). 9. Adequate renal function by estimated creatinine clearance =50 mL/min as calculated using the Cockcroft-Gault method. 10. Estimated life expectancy of at least 12 weeks. 11. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 12. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 13. Patients of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for at least 60 days after the last dose of assigned treatment. Patients of non-childbearing potential must meet at least one of the following criteria: • Have undergone a documented hysterectomy and/or bilateral oophorectomy; • Have medically confirmed ovarian failure; or • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state. All other patients (including patients with tubal ligations) will be considered to be of childbearing potential. Are the trial subjects under 18? no Number of subjects for t
Exclusion criteria
Exclusion criteria: 1. Non-epithelial tumors, or ovarian tumors with low malignant potential (ie, borderline tumors). 2. Mucinous tumors. 3. Patients for whom, in the opinion of the Investigator, there is clinical benefit to administer bevacizumab as a first-line treatment and for whom bevacizumab is approved and available in this setting. 4. Cancer for which intraperitoneal cytotoxic chemotherapy is planned. 5. Prior systemic anti-cancer treatment for EOC, FTC, or PPC. 6. Prior immunotherapy with IL-2, IFN-a, or anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways. 7. Major surgery (other than debulking surgery) for any reason within 4 weeks prior to randomization and/or incomplete recovery from surgery. 8. Known brain, leptomeningeal, or spinal cord metastases. 9. Current or prior use of immunosuppressive medication within 7 days prior to randomization, except the following: intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); systemic corticosteroids at physiologic doses =10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity reactions [eg, computed tomography (CT) scan premedication]. 10. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents except patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism not requiring immunosuppressive treatment. 11. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism. 12. Active and clinically significant bacterial, fungal or viral infection, any positive tests for hepatitis B (HBV), hepatitis C (HCV) indicating acute or chronic infection(positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive), known history of a positive human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness. 13. Administration of a live vaccine within 30 days prior to study entry. 14. Known severe hypersensitivity reactions to monoclonal antibodies, carboplatin, or paclitaxel or other platinum-containing compounds (NCI CTCAE v4.03 Grade =3). 15. Persisting NCI CTCAE v4.03 Grade >1 toxicity related to prior therapy. 16. Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, lobular carcinoma in situ (LCIS), or ductal carcinoma in situ (DCIS). 17. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the study. 18. Participation in other clinical studies involving investigational drug(s) within 4 weeks prior to study randomization and/or during study participation. 19. Other severe/severe acute or chronic medical, including colitis, inflammatory bowel disease, and pneumonitis, or psychiatric condition, including recent (within the past year) or active su
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To demonstrate that avelumab in combination with platinum-based chemotherapy followed by avelumab maintenance (Arm C) is superior to platinum-based chemotherapy alone followed by observation (Arm A) in prolonging progression free survival (PFS) in patients with previously untreated epithelial ovarian cancer (EOC). 2. To demonstrate that platinum-based chemotherapy alone followed by avelumab maintenance (Arm B) is superior to platinum-based chemotherapy alone followed by observation (Arm A) in prolonging PFS in patients with previously untreated EOC.;Secondary Objective: • To compare Arm C and Arm B to Arm A in patients with untreated EOC, with respect to overall survival. • To evaluate the anti-tumor activity in each arm. • To evaluate the overall safety profile in each arm. • To evaluate the pharmacokinetics of paclitaxel and carboplatin alone and in combination with avelumab. • To evaluate the PK of avelumab alone and in combination with carboplatin-paclitaxel (Arms B and C). • To evaluate the immunogenicity of avelumab alone and in combination with carboplatinpaclitaxel (Arms B and C). • To evaluate candidate predictive biomarkers of sensitivity or resistance to avelumab in combination with and/or following carboplatin-paclitaxel in pre-treatment tumor tissue, that may aid in the identification of patient subpopulations most likely to benefit from treatment. • To evaluate patient reported outcome in each treatment arm in patients with previously untreated EOC including the assessment of treatment side effects and diseaserelated symptoms.;Primary end point(s): • Progression-free survival (PFS) as determined by blinded independent central review (BICR) by RECIST version 1.1;Timepoint(s) of evaluation of this end point: As in protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Efficacy: Overall survival (OS), PFS by Investigator assessment as well as Objective response (OR), Duration of response (DR), Maintenance PFS by BICR assessments and Investigator assessment, pathological Complete Response (pCR), PFS2, and PFS by Gynecological Cancer Intergroup (GCIG) criteria • 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) • Patient-Reported Outcomes: FOSI-18 and EuroQoL5 Dimension (EQ-5D-5L) • Pharmacokinetics: PK parameters, including Ctrough, Cmax, volume of distribution (Vd), clearance (CL), area under the concentration time curve (AUC) for avelumab, paclitaxel, and carboplatin, as data permit • Immunogenicity: 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);Timepoint(s) of evaluation of this end point: As in protocol | — |
Countries
Bulgaria, Canada, Croatia, Estonia, Germany, Hong Kong, Hungary, Ireland, Italy, Japan, Korea, Republic of, Latvia, Mexico, Netherlands, Poland, Romania, Russian Federation, Singapore, Slovakia, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed