Intra-lesional Nivolumab Therapy for Limited Cutaneous Kaposi Sarcoma

NCT03316274 | Completed Early Phase 1 DMC FDA Drug

• 3 other identifiers: 17872NCI-2018-02529P30CA082103
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Infection with Kaposi sarcoma herpesvirus (KSHV, or human herpesvirus-8 (HHV-8)) causes Kaposi sarcoma (KS). These virally associated diseases occur more frequently in HIV-infected individuals, but can also be found in HIV-uninfected population. Evolution of immunosuppressive mechanisms presumably plays a permissive role in the development, progression and recurrence of these virus-associated cancers and pre-cancers. Currently, available treatment options for these lesions are imperfect and there is no clear treatment for patients with limited cutaneous Kaposi sarcoma (KS). Radiation and injection of vinblastine both have side effects that may not be acceptable. Nivolumab has been used to treat more extensive KS when given intravenously. To the best of the investigator's knowledge, this is the first study to evaluate the safety of intra-lesional injections of nivolumab in patients with KS.

Conditions

Kaposi Sarcoma; HIV/AIDS; Immunosuppression

Outcome Measures

Primary Outcomes (2)

• Number participants with Dose Limiting Toxicities (DLT) (Cohort A)

  The number of participants with DLTs will defined as treatment-related, grade 3-5 adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  6 months

• Maximum Tolerated Dose (MTD) (Cohort A)

  The MTD is defined as the dose at which no more than 1/6 patients experience a DLT

  6 months

Secondary Outcomes (9)

• Median percent change in absolute CD3 cells (CD3+) / CD4+ cells

  6 months

• Median percent change in cytotoxic T cells with CD8 surface protein (CD8+) T cells /Granzyme+ T cytotoxic T cells

  6 months

• Median percent change in CD56+ natural killer (NK) cells

  6 months

• Median percent change in CD4+FOXP3-effector T cells

  6 months

• Median percent change in CD4+FOXP3+regulatory T cells

  6 months

Study Arms (3)

Nivolumab (Cohort A-Safety)

EXPERIMENTAL

Participants will receive a 10mg (or 1 mL) injection into a single KS lesion in the skin, every 2 weeks for 4 doses.

Drug: Nivolumab

Nivolumab (Cohort B-Expansion)

EXPERIMENTAL

Participants from Cohort A with at least 1 lesion that is left untreated and additional participants receive injections in into up to 2 KS lesions in the skin, every 2 weeks for 4 doses. The injected volume will not exceed 10 mg (or 1 mL) each time. Lesions will be evaluated at week 26, and participants with lesion improvement may enroll in Cohort B-PLUS to receive additional injections.

Drug: Nivolumab

Nivolumab (Cohort B-PLUS)

EXPERIMENTAL

Participants in Cohort B whose injected lesions achieved partial response or complete response by week 26 and who did not experience any serious adverse events, are permitted to receive additional injections up to 4 residual KS lesions (total volume 10 mg in 1 mL) every 2 weeks for up to 4 additional doses. Lesions will be assessed again after 26 weeks.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Given via intralesional injection

Also known as: Nivolumab Injection, Opdivo

Nivolumab (Cohort A-Safety); Nivolumab (Cohort B-Expansion); Nivolumab (Cohort B-PLUS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For screening: Participants must have histologically confirmed KS with active cutaneous disease and have less than 25 lesions. For enrollment: Participants must have histologically confirmed KS in the research skin biopsy performed during the screening visit.
• Participants 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: Participants may eligible even if some KS lesions that have previously been treated with local therapy, as long as other untreated KS lesions are measurable as defined in the protocol.
• For the initial safety cohort (cohort A), participants have to be treatment-experienced, i.e. at least one of the KS skin lesions has been persisted despite having been treated with:
• systemic chemotherapy; OR
• or more topical therapy, local radiation, surgery, or intra-lesional cytotoxic therapy.
• For the expansion cohort (cohort B), participants can be either treatment-experienced or treatment-naïve.
• For the extension cohort (cohort B-plus), participants 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.
• Age \>= 18 years.
• If human immunodeficiency virus (HIV)-infected, participants must have:
• HIV-1 infection, documented by any federally approved, licensed HIV rapid test performed in conjunction with screening (or 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/mm3
• 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 anti-retroviral (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, participants must have documentation of a negative HIV result by any federally approved, licensed HIV test within the last 12 months.
• Adequate organ function defined as follows:

You may not qualify if:

• 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 to 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Sarcoma, Kaposi; Acquired Immunodeficiency Syndrome

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chia-ching Wang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 20, 2017
• Study Start: May 7, 2018
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)