Ignite Creation Date:
2024-05-06 @ 4:12 PM
Last Modification Date:
2024-10-26 @ 2:05 PM
Study NCT ID:
NCT04902443
Status:
RECRUITING
Last Update Posted:
2024-07-05
First Post:
2021-05-25
Brief Title:
Pomalidomide and Nivolumab in People With Virus-Associated Malignancies With or Without HIV
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Study of Pomalidomide and Nivolumab in Patients With Virus-Associated Malignancies With or Without HIV
Status:
RECRUITING
Status Verified Date:
2024-10-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 8Kaposi sarcoma herpesvirus HHV8KSHV human papilloma virus HPV hepatitis B or C virus HBVHCV 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 andor 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
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 8Kaposi sarcoma herpesvirus HHV8KSHV human papilloma virus HPV hepatitis B or C virus HBVHCV 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 andor 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
Detailed 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 andor 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-associated malignancies
Checkpoint inhibitors used alone have been shown to have some activity in certain virus-induced tumors eg Hodgkin and non-Hodgkin lymphomas Merkel cell carcinoma and HPV-associated nasopharyngeal cancer It is thus rational to explore combination strategies that overcome viral-mediated immune evasion and provide potentially better immunologic anti-tumor activity
Objectives
-Assess the safety and tolerability of pomalidomide plus nivolumab PomNivo in participants with virus-associated solid malignancies
Eligibility
Age greater than or equal to 18 years
Histologically or cytologically proven selected virus-associated tumors that are systemic metastatic or locally advanced and not amenable to curative treatment options or relapsedrefractory to first-line therapy
For solid tumors or hematologic malignancies at least one measurable disease
At least five measurable cutaneous KS lesions with no previous local radiation surgical or intralesional cytotoxic therapy to these measurable lesions
ECOG Performance Status PS less than or equal to 2
Participants must be willing to give informed consent
Participants can be HIV positive or negative
Antiretroviral therapy ART for HIV patients
Participants receiving other investigational agents will not be eligible
Design
This is a Phase I study assessing the safety and efficacy of a fixed dose of nivolumab combined with increasing doses of pomalidomide in participants with viral associated malignancies
Up to 6 participants treated in a 33 dose de-escalation schema for pomalidomide using one dose de-escalation and one dose escalation levels
Following identification of an optimal dose an expansion phase will be initiated through a protocol amendment Up to 30 participants will be enrolled Of these 12 participants must have a KS diagnosis and 12 participants must have EBV andor KSHV-associated lymphomas
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
Pomalidomide will be administered as an oral planned starting dose of 3 mg daily Pomalidomide will be given from day 1 to day 21 of each cycle
Participants will receive therapy up to 24 cycles or until unacceptable toxicity clinical progression the participant s request to discontinue therapy or PI decision
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 andor 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-associated malignancies
Checkpoint inhibitors used alone have been shown to have some activity in certain virus-induced tumors eg Hodgkin and non-Hodgkin lymphomas Merkel cell carcinoma and HPV-associated nasopharyngeal cancer It is thus rational to explore combination strategies that overcome viral-mediated immune evasion and provide potentially better immunologic anti-tumor activity
Objectives
-Assess the safety and tolerability of pomalidomide plus nivolumab PomNivo in participants with virus-associated solid malignancies
Eligibility
Age greater than or equal to 18 years
Histologically or cytologically proven selected virus-associated tumors that are systemic metastatic or locally advanced and not amenable to curative treatment options or relapsedrefractory to first-line therapy
For solid tumors or hematologic malignancies at least one measurable disease
At least five measurable cutaneous KS lesions with no previous local radiation surgical or intralesional cytotoxic therapy to these measurable lesions
ECOG Performance Status PS less than or equal to 2
Participants must be willing to give informed consent
Participants can be HIV positive or negative
Antiretroviral therapy ART for HIV patients
Participants receiving other investigational agents will not be eligible
Design
This is a Phase I study assessing the safety and efficacy of a fixed dose of nivolumab combined with increasing doses of pomalidomide in participants with viral associated malignancies
Up to 6 participants treated in a 33 dose de-escalation schema for pomalidomide using one dose de-escalation and one dose escalation levels
Following identification of an optimal dose an expansion phase will be initiated through a protocol amendment Up to 30 participants will be enrolled Of these 12 participants must have a KS diagnosis and 12 participants must have EBV andor KSHV-associated lymphomas
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
Pomalidomide will be administered as an oral planned starting dose of 3 mg daily Pomalidomide will be given from day 1 to day 21 of each cycle
Participants will receive therapy up to 24 cycles or until unacceptable toxicity clinical progression the participant s request to discontinue therapy or PI decision
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 21-C-0023 | None | None | None |