NRG-GY009

A Randomized, Phase II/III Study of Pegylated Liposomal Doxorubicin and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin/Bevacizumab and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin/Bevacizumab in Platinum-Resistant Ovarian Cancer

Objective

To estimate the probability of a dose-limiting toxicity (DLT) following cycle 1 of experimental regimens (pegylated liposomal doxorubicin hydrochloride [pegylated liposomal doxorubicin] [PLD] and atezolizumab and PLD/bevacizumab and atezolizumab). (Safety lead-in) II. Estimate and compare the hazard of first progression or death (progression-free survival [PFS]) of each experimental regimen relative to the reference regimen, PLD and bevacizumab. (Phase II study) III. Estimate and compare the hazard of death and the hazard of first progression or death (PFS) of each experimental regimen relative to the reference regimen. (Phase III)

Study Arms

  • Experimental: Arm I (PLD, Atezolizumab)
  • Experimental: Arm II (PLD, Bevacizumab, Atezolizumab)
  • Active Comparator: Arm III (PLD, Bevacizumab)

Eligibility

  • Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial
  • High-grade ovarian cancer, including high grade serous; clear cell; endometrioid, grade 3; and others (adenocarcinoma, not otherwise specified [NOS]; mixed epithelial carcinoma; undifferentiated carcinoma); NOTE: low grade serous, mucinous and carcinosarcoma histologies are excluded due to their different underlying genomic features and/or clinical behavior; ovarian cancer = ovarian, fallopian tube or primary peritoneal cancer; required data element: submission of pathology report
  • Recurrent, platinum-resistant ovarian cancer (defined as progression within < 6 months from completion of platinum-based therapy; the date should be calculated from the last administered dose of platinum therapy)
  • 1-2 prior regimens (including primary therapy); hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit
  • Measurable disease (defined by RECIST v1.1) or evaluable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of cancer antigen [CA]25 >= 2 x upper limit of normal [ULN])
  • Performance status 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
  • Platelets >= 100,000/mcl (within 14 days prior to registration)
  • Hemoglobin (Hgb) >= 8 g/dl (within 14 days prior to registration)
  • Creatinine =< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
  • Urine protein creatinine (UPC) ratio must be < 1.0 (within 14 days prior to registration); if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be < 1000 mg for patient enrollment); UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
  • Total bilirubin =< 1.5 x ULN (patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (AST and/or ALT =< 5 x ULN for patients with liver involvement) (within 14 days prior to registration)
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (or on stable dose of therapeutic anticoagulation, such as low-molecular-weight heparin, warfarin or rivaroxaban)

Thyroid-stimulating hormone (TSH) within normal limits (Euthyroid patients on thyroid replacement therapy allowed provided TSH < ULN)

NCT ID

NCT02839707