Trial of Ixazomib for Kaposi Sarcoma

NCT04305691 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: AMC-107NCI-2020-01138UM1CA121947
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 11

Brief Summary

This phase II trial studies how well ixazomib works in treating patients with Kaposi sarcoma. Ixazomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Skin; Kaposi Sarcoma

Keywords

Kaposi Sarcoma; HIV; Skin; ixazomib

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  The binomial proportion and its 90% one-sided confidence interval will be used to estimate the overall response rate. Response and progression will be evaluated in this study using the acquired Immunodeficiency syndrome (AIDS) Clinical Trials Groups (ACTG) response criteria for Kaposi sarcoma, as outlined in the AIDS Malignancy Consortium (AMC) Kaposi sarcoma Response Evaluation Manual of Procedures (MOP).

  Up to 4 weeks post treatment

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 4 weeks post treatment

• Change in Kaposi-sarcoma associated herpes virus (KSHV) viral load (VL)

  Baseline up to 4 weeks post treatment

• Change in CD4 counts

  Baseline up to 4 weeks post treatment

• Change in human immunodeficiency virus (HIV) VL

  Baseline up to 4 weeks post treatment

• Complete response rate

  Up to 4 weeks post treatment

Other Outcomes (1)

• Change in quality of life

  Baseline up to 4 weeks post treatment

Study Arms (1)

Treatment (ixazomib)

EXPERIMENTAL

Patients receive ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response may continue treatment for an additional 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Ixazomib Citrate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ixazomib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (ixazomib)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Participants must have histologically or cytologically confirmed cutaneous Kaposi sarcoma. Participants must have measurable disease with a minimum of five bi-dimensionally measurable KS cutaneous marker lesions. If fewer than five bi-dimensionally measurable marker lesions are available, the total surface area of the marker lesion(s) must be \>= 700 mm\^2
• Participants must have documentation of HIV status. If HIV negative, documentation of a negative HIV rapid test within 21 days before enrollment. If HIV positive, documentation of HIV-1 infection by means of any one of the following:
• Documentation of HIV diagnosis in the medical record by a licensed health care provider
• Documentation of receipt of antiretroviral therapy (ART) (at least two different medications that do not constitute a prescription for pre exposure prophylaxis \[PrEP\]) by a licensed health care provider. Documentation may be a record of an ART prescription in the participant's medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant's name
• HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating \> 1000 RNA copies/mL
• Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or Multispot HIV-1/HIV-2 Rapid Test or HIV Antibody HIV-1/HIV-2 Differentiation Assay
• Note: The term "licensed" refers to a kit that has been certified or licensed by an oversight body within the participating country and validated internally (e.g., United States \[U.S.\] Food and Drug Administration \[FDA\]). WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an extracellular interactome assay (E/CIA )that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
• Life expectancy of greater than 3 months
• Absolute neutrophil count: \>= 1,000/mm\^3 (within 21 days before enrollment)
• Hemoglobin: \> 8 g/dL (within 21 days before enrollment)
• Platelets: \>= 75,000/mm\^3 (within 21 days before enrollment). Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before study enrollment
• Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN) (within 21 days before enrollment)
• If the elevated bilirubin is felt to be secondary to indinavir or atazanavir therapy, then subjects will be allowed on protocol without any limit on the total bilirubin if the direct bilirubin is normal

You may not qualify if:

• Participants who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ixazomib or other agents used in study
• Chronic systemic treatment using strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort is not allowed. Patients who are on chronic use of strong CYP3A inducers must come off 14 days before receiving ixazomib treatment. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection; uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months; or psychiatric illness/social situations that would limit compliance with study requirements. This includes infections requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment but excludes ongoing antibiotic therapy for opportunistic infection (OI) prophylaxis
• Participants with a second prior or concurrent malignancy that has a natural history or treatment regimen that has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Pregnant women are excluded from this study because ixazomib is expected to cause fetal harm if used during pregnancy. It is not known if ixazomib is excreted into breast milk, but due to the potential for serious adverse events in a nursing infant, breastfeeding must be discontinued during therapy and for 90 days after the last ixazomib dose
• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before entering the study
• Participants who have not recovered from other adverse events due to prior anti-cancer therapy (i.e., have residual toxicity \> grade 1), excluding alopecia
• Participants who are seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). All participants will be required to be screened for hepatitis B. Participants with resolved infection (i.e. participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface antigen (anti-HBs) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV deoxyribonucleic acid (DNA) levels. Participants who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of hepatitis B virus (HBV) vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
• Participants with grade 2 or higher peripheral neuropathy (i.e., painful neuropathy) on clinical examination during the screening period
• Major surgery within 14 days before enrollment
• Participants with symptomatic visceral Kaposi sarcoma
• Participants who have had prior treatment of Kaposi sarcoma with a proteasome inhibitor within the last 2 years or with ixazomib at any time.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• AIDS Malignancy Consortium: lead

Study Sites (11)

UC San Diego

San Diego, California, 92093, United States

RECRUITING

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

RECRUITING

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

Abramson Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, 19106, United States

RECRUITING

Thomas Street Clinic

Houston, Texas, 77004, United States

RECRUITING

Thomas Street Clinic

Houston, Texas, 77004, United States

RECRUITING

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma, Kaposi

Interventions

ixazomib

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

Study Officials

• Erin Reid, MD

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erin Reid, MD

CONTACT

(858) 822-6100; egreid@ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 12, 2020
• Study Start: November 7, 2023
• Primary Completion (Estimated): March 15, 2029
• Study Completion (Estimated): March 15, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (11)