PREVIOUSLY UNTREATED ADVANCED OVARIAN CANCER MedDRA version: 20.0 Level: LLT Classification code 10033130 Term: Ovarian cancer NOS System Organ Class: 100000004864
Conditions
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (according to American Joint Committee on Cancer (AJCC)/UICC TNM and International Federation of Gynecology and Obstetrics (FIGO) Staging System 2014 edition), including carcinosarcoma with high-grade serous component. 2. Patients must be candidates for bevacizumab in combination with platinum based chemotherapy and previously untreated. 3. Must have completed a primary surgical debulking procedure, or be candidates for neoadjuvant chemotherapy with planned interval debulking surgery. a. Patients who completed primary debulking must have had incompletely resected disease that is macroscopically/grossly visible and at least with lesions >1 mm per operative records and be randomized at a maximum of 8 weeks after surgery. b. For patients who are candidates for neoadjuvant chemotherapy, the diagnoses must have been confirmed by: - Core tissue (not fine-needle aspiration) biopsy is required for diagnosis. The tissue must be consistent with inclusion criteria #1 above. - Stage IIIC–IV documented via imaging or surgery (without attempt at cytoreduction). - Serum CA-125/CEA ratio >25. If the serum CA-125/CEA ratio is <25, then workup should be negative for the presence of a primary gastrointestinal or breast malignancy (<6 weeks before start of neoadjuvant treatment). - 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 25 slides, together with an accompanying original Hemotoxylin and Eosin (H&E) slide. 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. - Sites may randomize/enroll patients who meet all other eligibility criteria while awaiting central confirmation of tissue acceptance, but must provide additional tumor samples in the event that the central lab review shows insufficient sample quality. 5. Eastern Cooperative Group (ECOG) performance status 0-1. 6. Age =18 years (or =20 years in Japan). 7. Adequate bone marrow function including: absolute neutrophil count (ANC) =1,500/mm3 or 1.5 x 109/L; Platelets =100,000/mm3 or =100 x 109/L; hemoglobin =9.0 g/dL (may have been transfused). 8. Adequate hepatic function defined by a total bilirubin level =1.5 x upper limit of normal range (ULN), an ALT/AST level =2.5 x ULN. 9. Adequate renal function by estimated creatinine clearance =60 mL/min as calculated using the Cockcroft-Gault method or by 24 hour urine collection for creatinine clearance or according to local institutional standard method. 10. Adequate blood coagulation parameters: International normalized ratio (INR) =1.5 and aPTT <1.2 times the upper limit of normal. 11. Ability to swallow oral study drugs. 12. 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. 13. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 14. Patients of childbearing potential and at risk for pregnancy must agree to use 2 methods of contraception (at least one of which is considered to be highly effective with low user dependency) as outlined in this protocol for the duration of the study and fo
Exclusion criteria
Exclusion criteria: 1. Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors. 2. Patients for whom intraperitoneal cytotoxic chemotherapy is planned. 3. Prior exposure to immunotherapy with interleukin (IL)-2, interferon alpha (IFN-a), an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, excluding therapeutic anticancer vaccines. 4. Prior treatment with a PARP inhibitor. 5. Prior treatment with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab. 6. Major surgery (other than debulking or exploratory surgery for ovarian cancer) for any reason within 4 weeks prior to randomization and/or incomplete recovery from surgery. 7. Prior radiotherapy to any portion of the abdominal cavity or pelvis. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease. 8. Prior targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their ovarian, peritoneal primary or fallopian tube carcinoma. 9. Prior organ transplantation including allogenic stem cell transplantation. 10. Diagnosis of Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). 11. 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 enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. 12. Current or anticipated use within 7 days prior to the first dose of talazoparib or anticipated use during the study of a P-glycoprotein (P-gp) inhibitor, P-gp inducer, or breast cancer resistance protein (BCRP) inhibitor. 13. Current use of immunosuppressive medication at the time of randomization, EXCEPT for the following: (a) intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection); (b) Systemic corticosteroids at physiologic doses =10 mg/day of prednisone or equivalent; (c) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 14. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism not requiring immunosuppressive treatment are eligible. 15. Clinically significant (ie, active) cardiovascular disease: cerebrovascular accident/stroke (140 mm Hg or diastolic >90 mm Hg documented by 2 blood pressure readings taken at least 1 hour apart. Use of antihypertensive medications to control blood pressure (BP) is allowed. 17. Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that avelumab in combination with platinum-based chemotherapy followed by avelumab plus talazoparib maintenance is superior to platinum-based chemotherapy plus bevacizumab followed by bevacizumab maintenance in prolonging progression-free survival (PFS) in patients with advanced ovarian cancer with defects in DNA damage repair (DDR+).;Secondary Objective: - To demonstrate that avelumab in combination with platinum-based chemotherapy followed by avelumab plus talazoparib maintenance is superior to platinum-based chemotherapy plus bevacizumab followed by bevacizumab maintenance in prolonging overall survival (OS) in patients with advanced ovarian cancer with defects in DNA damage repair (DDR+). - To demonstrate that avelumab in combination with platinum-based chemotherapy followed by avelumab plus talazoparib maintenance is superior to platinum-based chemotherapy plus bevacizumab followed by bevacizumab maintenance in prolonging PFS in patients with advanced ovarian cancer unselected for DDR status. Refer to protocol for the full list of Secondary Objectives.;Primary end point(s): Progression-Free Survival (PFS) as determined based on Blinded Independent Central Review (BICR) assessment per RECIST v1.1 in patients with newly diagnosed advanced ovarian cancer with defects in DNA damage repair (DDR+).;Timepoint(s) of evaluation of this end point: As per protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): OS in patients with tumors that are DDR+ and in patients unselected for DDR status. - PFS based on BICR assessment per RECIST v1.1 in patients unselected for DDR status. - PFS based on investigator assessment per RECIST v1.1 in patients with tumors that are DDR+ and in patients unselected for DDR status. - PFS2 based on investigator assessment in patients with tumors that are DDR+ and in patients unselected for DDR status. - PFS based on investigator assessment per Gynecological Cancer Intergroup (GCIG) criteria in patients with tumors that are DDR+ and in patients unselected for DDR status. - AEs (as graded by NCI CTCAE v4.03); laboratory abnormalities (as graded by NCI CTCAE v4.03); vital signs (blood pressure, pulse rate); electrocardiograms (ECGs). - PK parameters, including Ctrough and Cmax for avelumab and Ctrough for talazoparib. - Anti-drug antibodies (ADA) and neutralizing antibody (NAb) against avelumab. - Disease related symptoms and treatment side effects as measured by the NCCN-FACT FOSI-18 and health-related quality of life (HRQOL) as measured by NCCN-FACT FOSI-18 and the EuroQol Group 5-Dimension 5-Level (EQ-5D-5L). - PD-L1 expression, TMB, genomic scarring and the presence of defects in select genes, considered critical to effective DDR, in baseline tumor tissue. - Assessment of defects in a panel of key oncogenes, including several considered critical to effective DDR and TMB in ctDNA at baseline.;Timepoint(s) of evaluation of this end point: As per protocol | — |
Countries
Australia, Belgium, Canada, Croatia, Czech Republic, Estonia, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Poland, Romania, Russian Federation, Singapore, Slovakia, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed