Phase II trial of Concurrent Anti-PD-L1 and SAbR for Patients with Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer (with safety lead-in)
- Parkland Health & Hospital System
Programmed death-1 receptor ligand (PD-L1) the ligand for PD-1 is a key therapeutic target in the reactivation of the immune response against multiple cancers. Pharmacologic inhibitors of PD-1 have also demonstrated significant anti-tumor activity and are currently under active clinical exploration. avelumab (MSB0010718C; anti-PD-L1 is a fully human anti-PD-L1 igG1 antibody that has shown promising efficacy and an acceptable safety profile in multiple tumor types.
Radiation therapy (RT) is one of the mainstream treatments of cancer therapy along with surgery and chemotherapy, yet RT is the only treatment that does not leave the patients immunocompromised (unlike chemotherapy) and keeps the dying tumor / antigen depot within the host (unlike surgery), providing an opportunity for antigen presentation. Therefore, RT is a rational choice to combine with immunotherapy for cancer treatment.
1. Female subjects aged >= 18 years.
2. Performance ECOG status of 0-2
3. Patient is able and willing to comply with protocol and study procedures for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up visits.
4. Adequate Physiologic function:
* Hematologic: Absolute neutrophil count (ANC) >= 1.5 x 109/L, platelet count >= 100 x 109/L, and hemoglobin >= 9 g/dL (may have been transfused)
* Hepatic: Total bilirubin level <= 1.5 x the upper limit of normal (ULN) range and AST and ALT levels <= 2.5 x ULN or AST and ALT levels <= 5 x ULN (for subjects with documented metastatic disease to the liver).
* Renal: Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
5. Pregnancy and contraception:
Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential.
Contraception: Women of child-bearing potential and their male partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry.,
6. Histologic diagnosis of recurrent epithelial ovarian ,fallopian ,peritoneal cancer
7. Patients with platinum sensitive ovarian cancer must have progressed through at least one platinum containing regimen for recurrent disease.
8. Patients with platinum resistant ovarian cancer must have progressed through at least one prior chemotherapy regimen for recurrent ovarian cancer.
9. Patients must have received at least one prior chemotherapy regimen and up to any number of prior systemic regimens including chemotherapy and molecular targeted therapy other than PD1/ PDL1/ PDL2 inhibitors.
10. Metastatic disease of at least two Non-CNS sites (including the index lesion to be treated) measurable by RECIST criteria with at least one site outside of the radiation field and evaluable by RECIST criteria for evaluation of response.
11. Ability to understand and the willingness to sign a written informed consent