Intra-lesional Nivolumab in Treating Patients with Cutaneous Kaposi Sarcoma
This phase I trial studies the side effects of nivolumab injected directly into the lesion and to see how well it works in treating patients with cutaneous Kaposi sarcoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
- For Screening: Patients must have histologically confirmed KS with active cutaneous disease and have less than 25 lesions.
- For enrollment: Patients must have histologically confirmed KS in the research skin biopsy performed during the screening visit.
- Patients must have measurable cutaneous KS disease, defined as: 1 or more marker lesion that is bi-dimensionally measurable, and >= 0.5cm in shortest dimension. These measurable lesions must not have received previous local radiation, surgical, or intralesional cytotoxic therapy that would prevent response assessment * Note: Patients may eligible even if some of their KS lesions that have previously been treated with local therapy, as long as they have other untreated KS lesions that are measurable as defined in the protocol
- For the initial safety cohort (cohort A), patients have to be treatment-experienced, i.e. at least one of their KS skin lesions has been persisted despite having been treated with: * Systemic chemotherapy; OR * 1 or more topical therapy, local radiation, surgery, or intra-lesional cytotoxic therapy For the expansion cohort (cohort B), patients can be either treatment-experienced or treatment-naive. For the extension cohort (cohort B-plus), patients are from the expansion cohort above (cohort B) who have achieved partial response (PR) or complete response (CR) in their injected KS lesion at week 26 or later.
- If HIV-infected, patients must have: * HIV-1 infection, documented by any federally approved, licensed HIV rapid test performed in conjunction with screening (or enzyme-linked immunosorbent assay (ELISA), test kit, and confirmed by Western blot or other approved test). Alternatively, this documentation may include a record demonstrating that another physician has documented the participant's HIV status based on either: 1) approved diagnostic tests, or 2) the referring physician's written record that HIV infection was documented, with supporting information on the participant’s relevant medical history and/or current management of HIV infection * CD4 >= 350 cells/mm^3 * HIV-1 viral load below the limit of detection by commercial assays (< 75 copies/mL) * Participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management. Participants should be documented to be on an effective combination antiretroviral therapy (ART) regimen, generally a 3-drug regimen based on Department of Health and Human Services (DHHS) treatment guidelines by a licensed health care provider. Participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 12 weeks following enrollment
- If HIV-uninfected, patients must have documentation of a negative HIV result by any federally approved, licensed HIV test within the last 12 months
- Leukocytes > 3,000/mcL
- Absolute neutrophil count > 1,000/mcL
- Hemoglobin > 10 g/dL
- Platelets > 100,000/mc
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) < 2.5 x institutional upper limit of normal (ULN)
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional ULN
- Creatinine < 1.5 x institutional ULN
- Participants must be purified protein derivative (PPD) negative. Alternatively, the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay can be used. An individual is considered positive for M. tuberculosis infection if the IFN-gamma response to tuberculosis (TB) antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control). The result must be obtained within 12 months prior to enrollment. PPD positive (or QuantiFERON assay positive) participants are permitted if prophylaxis has been completed prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 1
- Karnofsky >= 70%
- The effects of nivolumab on the developing fetus are unknown. Therefore, only the following patients should be enrolled: * Woman of child-bearing potential (WOCBP, defined as a sexually mature woman who has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months} must have negative serum pregnancy test within 7 days before starting study treatment in WOCBP and willingness to adhere to acceptable forms or birth control (a physician-approved contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner). WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 6 months after the last dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study (including the time after last dose previously mentioned), she (or the participating partner) should inform the treating physician immediately * Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product
- Prior systemic KS-directed treatments or investigational modalities =< 5 half-lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy to grade 1 or less
- Presence of any visceral KS (including KS-associated lymphedema) requiring systemic chemotherapy. This includes, but not limited to, any symptomatic visceral KS or asymptomatic pulmonary KS
- Hypersensitivity to nivolumab or any of its excipients
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Opportunistic infection within the last 3 months
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. This does not apply for participants in the extension cohort (cohort B-plus).
- Active systemic immunosuppressive therapy
- The use of prednisone or equivalent 10mg or greater a day that cannot be discontinued with more than 7 consecutive days of steroids within the prior 2 weeks
- Prior organ allograft or allogeneic transplantation, if the transplanted tissue is still in place
- Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure
- Major surgery =< 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy
- Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Any condition that confounds the ability to interpret data from the study
Locations & Contacts
Trial Objectives and Outline
I. To determine the safety and tolerability of four intra-lesional injections of nivolumab given every two weeks to treat Kaposi sarcoma (KS).
I. To estimate the changes in cytotoxic T cells and regulatory T cells in biopsy from treated lesions as determined by immunohistochemistry and flow cytometry.
II. To estimate the changes in cytotoxic T cells and regulatory T cells in the peripheral blood as determined by flow cytometry.
III. To estimate the changes in PD-1/PD-L1 expression as determined by immunohistochemistry in biopsy from treated lesions.
I. To estimate the overall response rates (defined per The Acquired Immunodeficiency Syndrome [AIDS] Clinical Trials Group [ACTG)] criteria for KS) at 26 weeks after the first dose of nivolumab separately, for the treated and untreated lesions (Cohort A and B).
II. To estimate the overall response rates (defined per ACTG criteria for KS) at 26 weeks after the fifth dose of nivolumab separately, for treated and untreated lesions (Cohort B-plus).
III. To determine the duration of response per treated lesion.
IV. To characterize tissue and peripheral burden of human herpesvirus-8 (HHV-8), human immunodeficiency virus (HIV), and other related viruses (e.g. cytomegalovirus [CMV]).
Patients receive nivolumab subcutaneously (SC) on day 1. Treatment repeats every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients whose KS lesion are improving may receive 4 additional cycles of nivolumab in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 and 26 weeks.
Trial Phase & Type
UCSF Medical Center-Mount Zion
Chia-Ching (Jackie) Wang
Secondary IDs NCI-2018-02529, 17-23060
Clinicaltrials.gov ID NCT03316274