Phase II Clinical Trial Combining the Hedgehog Inhibitor Vismodegib With the PD-L1 Inhibitor Atezolizumab in Patients With Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Ronald Buckanovich
Summary
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.
Description
While 5-year survival rates for early stage disease are approximately 90%, survival drops to 30% in advanced stage disease. Symptoms preceding diagnosis are often non-specific and vague. Moreover, there is no effective screening test. As a result, over 75% of patients are diagnosed with advanced stage disease, which leads to the high mortality rate. Regardless of BRCA mutation status, patients who develop recurrent disease will all ultimately progress to develop therapy resistant disease and ultimately die. The use of PARP inhibitor maintenance therapy after either a complete or partial respon…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * 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 * Measurable or non-measurable but evaluable disease per RECIST v1.1 {Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that sit…
Interventions
- DrugVismodegib
A 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.
- DrugAtezolizumab
Atezolizumab 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.
Location
- UPMC Hillman Cancer CenterPittsburgh, Pennsylvania