A Phase I Study of Pomalidomide and Nivolumab in Patients With Virus-Associated Malignancies With or Without HIV
National Cancer Institute (NCI)
Summary
Background: Less toxic and more effective treatments are needed for cancers caused by viruses. These cancers include Hodgkin and non-Hodgkin lymphoma, hepatocellular carcinoma, head and neck cancer, nasopharyngeal carcinoma, gastric cancer, anal cancer, cervical cancer, vaginal cancer, vulvar cancer, penile cancer, Merkel cell carcinoma, Kaposi sarcoma, and leiomyosarcoma. Researchers want to see if a combination of drugs can help. Objective: To find a safe dose of pomalidomide plus nivolumab in people with cancers caused by viruses. Eligibility: Adults ages 18 or older who have cancers caused by Epstein Barr virus (EBV), human herpes virus 8/Kaposi sarcoma herpesvirus (HHV8/KSHV), human papilloma virus (HPV), hepatitis B or C virus (HBV/HCV), and Merkel cell polyomavirus (MCPyV) that have not responded to previous treatments or have relapsed, or in adults who do not want to have surgery because of disfigurement or other risks. Adults who have HIV with any CD4 T cell count are eligible. Design: Participants will be screened with blood and urine tests, scans, and heart tests. They will have a physical exam. Their ability to perform normal daily activities will be assessed. They may have a tumor biopsy. Treatment will be given in 28-day cycles. Participants will take pomalidomide as a tablet by mouth for 21 days of each cycle, for up to 24 cycles. They will get nivolumab by intravenous infusion once each cycle. They will take an aspirin each day until 30 days after their last dose of the study drugs. Participants will keep a pill diary. They will bring it to their study visit at the end of each cycle. At these visits, some screening tests will be repeated. Participants with Kaposi sarcoma will have pictures taken of their lesions. Participants will give blood and saliva samples for research. They may have optional anal and/or cervical swabs. They may have optional biopsies. Participants will have a follow-up visit 30 days after they stop taking the study drugs, then every month for 100 days. Some screening tests will be repeated. Then they may by contacted by phone every 3 months for 9 months, and then every 6 months thereafter.
Description
Background: * There is an unmet need for less toxic and more effective treatments for virus-associated malignancies. * Pomalidomide induces polyfunctional T cell, NK cell, and dendritic cell activation. * Pomalidomide has shown promising activity in Kaposi sarcoma, likely due in part to immune modulation. * Downregulation and/or deregulation of immune surface markers by viruses can thwart immunologic therapy, which may be prevented or reversed by pomalidomide. * PD-L1 is expressed in virus-associated malignancies and modulation of PD-1 signaling is a promising approach to treatment of virus-a…
Eligibility
- Age range
- 18–99 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Histologically or cytologically proven selected virus-associated tumors that are systemic, metastatic or locally advanced and not amenable to curative treatment options or are relapsed/refractory to first-line therapy as appropriate for each tumor type as outlined below. Also, participants with eligible solid tumors, who after evaluation by an expert in the area are deemed to be potentially curable after extensive surgery, but refuse such surgical procedure due to associated disfigurement and/or morbidity, may be eligible for the study with the necessary informed consen…
Interventions
- DrugPomalidomide
Pomalidomide will be administered as an oral planned starting dose of 3 mg daily (dose escalation) or at an MTD of 4 mg (dose expansion). Pomalidomide will be given from day 1 to day 21 of each cycle.
- DrugNivolumab
Nivolumab will be administered IV at a dose of 480 mg at day one of each cycle, except for cycle one when it will be administered on day 8. One cycle equals 28 days
Location
- National Institutes of Health Clinical CenterBethesda, Maryland