This trial will treat patients with platinum resistant ovarian, fallopian tube or primary peritoneal cancer as defined by a progression free interval within six months of completion of most recent platinum-based treatment with a combination of vismodegib and atezolizumab. Despite recent improvements in treatment of ovarian cancer with the introduction of PARP inhibitors, response rates to therapy in the platinum resistant setting remain dismal with response rates of only 10-20% reported for single agent cytotoxic therapies. Given the poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of novel therapeutic candidates.
Signed Informed Consent Form
Ability to comply with the study protocol, in the investigator's judgment
Histologically or cytologically confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer
Platinum status, defined by disease progression during or following treatment with platinum-based chemotherapy within 6 months of completing therapy
Inability or unwillingness to swallow capsules
Inability or unwillingness to comply with study procedures
History of leptomeningeal disease
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Single group
Vismodegib
DrugA small-molecule SMO inhibitor designed to specifically target the hedgehog pathway, a known driver of BCC. It systemically inhibits hedgehog pathway signaling. Following mutation, SMO is released from the inhibitory effect of PTCH and moves to the cell surface, activating GLI. GLI travels to the nucleus and initiates transcription of target genes that regulate basal cell growth and proliferation.
Atezolizumab
DrugAtezolizumab is a humanized monoclonal antibody immune checkpoint inhibitor that selectively binds to PD-L1 to stop the interaction between PD-1 and B7.1 (CD80 receptors). The antibody still allows interaction between PD-L2 and PD-1.
Safety Determined by Dose Limiting Toxicities (DLTs)
Immune-related and other adverse events and/or serious adverse events related to treatment occurring within the first two cycles of treatment that require a dose reduction (Dose Limiting Toxicities (DLTs)). All adverse events will be tabulated by Type, Grade, Relatedness to Treatment and Expectedness, Cycle of Treatment, and by Dose Administered.
Objective Response Rate (ORR)
Confirmed complete response or partial response by RECIST 1.1. Per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Immune-modified Response Rate by imRECIST
Confirmed complete response or partial response by imRECIST. Per imRECIST: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Modified Response Rate by iRECIST
Confirmed complete response or partial response by iRECIST for immune-based therapeutics. Per iRECIST: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Overall Survival (OS)
Time from trial enrollment until death from any cause.
Progression-free survival (PFS)
Time from trial enrollment until disease progression by RECIST v1.1 or death from any cause. Progression as defined by RECIST v1.1 for target lesions: Progressive Disease (PD): smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase
Click on the lead sponsor to view all of their trials.
Ronald Buckanovich
Lead sponsor
University of Pittsburgh
Sponsor institution
Genentech, Inc.
Collaborator
