Ixazomib for Kaposi Sarcoma

Recruiting at 12 trial locations

Overseen By Erin Reid, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AIDS Malignancy Consortium

Must be taking: Antiretrovirals

Must not be taking: CYP3A inducers

Disqualifiers: Uncontrolled illness, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 48 weeks

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of the drug ixazomib in treating Kaposi sarcoma, a cancer that forms in the skin and other tissues. Ixazomib may help by stopping tumor cells from growing. The trial is suitable for individuals with Kaposi sarcoma who have visible skin lesions and, if HIV positive, have been on stable HIV treatment for at least four weeks. Participants will take ixazomib orally on specific days over a 28-day cycle, potentially continuing for up to 12 cycles if the treatment proves effective and is well tolerated. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you must stop taking any strong CYP3A inducers (like rifampin or St. John's wort) at least 14 days before starting the trial. If you are on antiretroviral therapy for HIV, you must be on a stable regimen for at least 4 weeks and avoid certain medications that reduce ixazomib exposure.

Is there any evidence suggesting that ixazomib is likely to be safe for humans?

Research shows that ixazomib is usually well-tolerated. Common side effects include low levels of blood cells, such as platelets and white blood cells, and digestive issues like diarrhea and constipation. Some individuals also experience nausea or fatigue. These side effects are typical for this kind of treatment.

Since this is a Phase 2 trial, earlier studies have already provided evidence that ixazomib is safe for humans. Additionally, the FDA has approved ixazomib for treating multiple myeloma, indicating its safety for that use.

Overall, while some side effects occur, they are generally manageable. It's important to discuss any concerns with the trial team to understand how these might affect participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Kaposi sarcoma?

Unlike the standard treatments for Kaposi Sarcoma, which typically include chemotherapy, radiation, or antiretroviral therapy, ixazomib uses a different approach by targeting and inhibiting proteasomes. Proteasomes are protein complexes that break down unneeded proteins in cells, and by inhibiting them, ixazomib disrupts cancer cell growth and survival. Researchers are excited about ixazomib because it is taken orally, potentially offering a more convenient and less invasive option compared to traditional intravenous chemotherapy. Additionally, its novel mechanism of action could provide an effective alternative for patients who do not respond well to existing treatments.

What evidence suggests that ixazomib might be an effective treatment for Kaposi sarcoma?

Studies have shown that ixazomib can help treat certain cancers by stopping tumor cells from growing. In earlier research, 96% of patients using ixazomib remained alive after 6 months. This treatment is especially known for its use in multiple myeloma and has shown promise in treating Kaposi sarcoma as well. By blocking certain enzymes, ixazomib aims to prevent these tumors from worsening. Early findings suggest it could be a useful option for people with Kaposi sarcoma. Participants in this trial will receive ixazomib to evaluate its effectiveness specifically for Kaposi sarcoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Erin Reid, MD

Principal Investigator

AIDS Malignancy Consortium

Are You a Good Fit for This Trial?

Adults with Kaposi sarcoma, good performance status (able to carry out daily activities), and adequate organ function can join. They must have measurable skin lesions, not be pregnant or breastfeeding, use contraception if of childbearing potential, and have a life expectancy over 3 months. HIV-positive patients need stable antiretroviral therapy for at least 4 weeks.

Inclusion Criteria

I can do most of my daily activities but might need help.

My platelet count is at least 75,000 without recent transfusions.

My kidney function, measured by creatinine levels, is normal or my creatinine clearance is at least 30 mL/min.

Exclusion Criteria

I haven't taken proteasome inhibitors for Kaposi sarcoma in the last 2 years, nor have I ever taken ixazomib.

I have a stomach or intestine condition that affects how I absorb pills or makes it hard for me to swallow.

I am not taking any strong medication that affects liver enzymes or St. John's wort.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ixazomib orally on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles.

48 weeks

3 visits per cycle (in-person)

Extended Treatment

Participants with complete or partial response may continue treatment for an additional 12 cycles.

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks, then periodically for up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ixazomib Citrate

Trial Overview

The trial is testing Ixazomib's effectiveness on Kaposi sarcoma by seeing if it can stop tumor growth. It involves taking the drug orally and monitoring its impact through health questionnaires and assessments.

How Is the Trial Designed?

Group I: Treatment (ixazomib) Experimental Treatment 3 Interventions

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.

Ixazomib Citrate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ninlaro for:

• Multiple myeloma

Approved in United States as Ninlaro for:

• Multiple myeloma

Approved in Canada as Ninlaro for:

• Multiple myeloma

Approved in Japan as Ninlaro for:

• Multiple myeloma

Who Is Running the Clinical Trial?

AIDS Malignancy Consortium

Lead Sponsor

Trials

64

Recruited

9,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ixazomib is the first oral proteasome inhibitor being tested for multiple myeloma, showing promising antitumor activity in preclinical studies and manageable side effects in early clinical trials.

Preliminary results indicate that ixazomib is effective both as a standalone treatment for relapsed/refractory multiple myeloma and in combination with other drugs for newly diagnosed patients, with ongoing Phase III studies to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. Richardson, PG., Moreau, P., Laubach, JP., et al.[2015]

In a review of 320 patients treated with immunotherapy, 9 men with HIV-associated Kaposi sarcoma (KS) showed a significant response, with 67% achieving partial or complete remission after treatment with nivolumab or pembrolizumab.

The treatment was well-tolerated, with no severe drug-related toxicities reported, and some patients even experienced an increase in CD4 counts, suggesting potential immune system benefits alongside tumor reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade. Galanina, N., Goodman, AM., Cohen, PR., et al.[2021]

Liposomal anthracyclines and paclitaxel have been identified as highly effective chemotherapy options for treating Kaposi's sarcoma (KS), showcasing significant progress in therapy for this disease.

New experimental agents, including antiangiogenesis drugs like TNP-470 and thalidomide, as well as oral 9-cis retinoic acid, are showing promise in early studies, indicating a potential for innovative treatments targeting the underlying causes of KS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy for Kaposi's sarcoma: recent advances and experimental approaches. Yarchoan, R.[2020]

Ixazomib is an orally taken proteasome inhibitor that works by blocking the β5 subunit of the proteasome, and it was approved by the FDA in 2015 for treating multiple myeloma in combination with lenalidomide and dexamethasone after at least one prior therapy.

Currently, ixazomib is being studied in Phase III trials for newly diagnosed multiple myeloma and other conditions, indicating its potential for broader applications in treating various cancers and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: First Global Approval. Shirley, M.[2018]

Ixazomib, an oral proteasome inhibitor, has been shown to significantly improve progression-free survival in patients with relapsed and/or refractory multiple myeloma when combined with lenalidomide and dexamethasone, with a median survival of 20.6 months compared to 14.7 months for the placebo group.

The drug works by selectively inhibiting the 20S proteasome, leading to the accumulation of proteins that induce stress and apoptosis in myeloma cells, making it a promising treatment option for patients who have undergone prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. Machida, M., Fukunaga, S., Hara, T.[2019]

The introduction of highly active antiretroviral therapy (HAART) has significantly decreased the prevalence and mortality rates of AIDS-related Kaposi's sarcoma, improving patient outcomes compared to the pre-HAART era.

Advancements in understanding the disease's molecular mechanisms have opened up new potential therapeutic strategies, alongside the effective use of conventional chemotherapy and immunomodulatory treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of AIDS-related Kaposi's sarcoma. Di Lorenzo, G., Konstantinopoulos, PA., Pantanowitz, L., et al.[2022]

In a study involving 18 male patients with progressive classical Kaposi sarcoma, the combination of nivolumab and ipilimumab showed a high overall response rate of 87%, indicating significant efficacy in this challenging condition.

The treatment resulted in a 6-month progression-free survival rate of 76.5%, with only 22% of patients experiencing severe adverse events, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS). Zer, A., Icht, O., Yosef, L., et al.[2022]

In a study of 12 patients with Kaposi's sarcoma (KS) treated with biologic or small molecule drugs, nine patients experienced KS onset or reactivation after a median of 6 months, particularly with drugs like rituximab and infliximab.

Despite the initial worsening of KS in some patients, all cases achieved a complete response after stopping the problematic drugs, indicating that careful monitoring and management of treatment are crucial for KS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kaposi's sarcoma, biologics and small molecules: Navigating the complex interplay between host immunity and viral biology. A case series with focused review of the literature. Brambilla, L., Maronese, CA., Zelin, E., et al.[2022]

Ixazomib, an oral proteasome inhibitor, significantly prolongs progression-free survival (PFS) in patients with relapsed and/or refractory multiple myeloma compared to placebo, as demonstrated in the TOURMALINE-MM1 trial involving adults who had received one to three prior therapies.

The treatment showed a favorable safety profile and resulted in a higher overall response rate, making ixazomib a valuable new option for patients with multiple myeloma who have undergone previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. Al-Salama, ZT., Garnock-Jones, KP., Scott, LJ.[2018]

In a phase 3 trial involving 722 patients with relapsed or refractory multiple myeloma, the addition of ixazomib to lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 20.6 months compared to 14.7 months for the placebo group.

The safety profile of ixazomib was comparable to placebo, with similar rates of serious adverse events and overall survival, although some specific side effects like thrombocytopenia and rash were more common in the ixazomib group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. Moreau, P., Masszi, T., Grzasko, N., et al.[2022]

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