Pomalidomide + Liposomal Doxorubicin for Kaposi Sarcoma

Not currently recruiting at 1 trial location

Overseen By Ramya M Ramaswami, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals, Aspirin

Must not be taking: Investigational agents

Disqualifiers: Primary effusion lymphoma, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 16

Duration: Ongoing until optimal tumor response or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for Kaposi sarcoma (KS), a cancer causing skin and sometimes internal lesions, often seen in people with HIV. Researchers are exploring how two drugs, pomalidomide (taken as a daily pill) and liposomal doxorubicin (given through an IV), might work together to treat KS. People with KS who have at least five measurable skin lesions and have not received certain types of local treatments may be a good fit for this trial. Participants will undergo a series of medical exams and take the treatment in cycles, with regular follow-up visits to monitor progress. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires a 3-week period without treatment (washout period) for most participants, except those with severe, progressive disease. This suggests you may need to stop some current medications, but it's best to discuss your specific situation with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of pomalidomide and liposomal doxorubicin is safe for people with Kaposi sarcoma (KS), including those who are HIV-positive. In earlier studies, patients took pomalidomide daily for 21 days in a 28-day cycle, along with liposomal doxorubicin. These studies found that the treatment was well-tolerated.

Participants in these studies did not experience severe side effects that required stopping treatment. Even those who had undergone many other treatments found this combination manageable.

Liposomal doxorubicin, a type of chemotherapy, causes fewer side effects than regular chemotherapy. It is less harmful to the body while remaining effective against cancer.

Overall, for those considering joining this trial, the available data suggests this treatment is generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using pomalidomide with liposomal doxorubicin for Kaposi Sarcoma because it offers a fresh approach to treatment. Unlike traditional chemotherapy drugs, pomalidomide is an immunomodulatory agent that can enhance the body's immune response while also directly attacking cancer cells. This dual action is different from the standard of care, which often relies solely on cytotoxic effects. Additionally, using liposomal doxorubicin helps to deliver the drug more precisely, minimizing damage to healthy tissues and potentially reducing side effects. This combination could mean a more effective and potentially safer treatment for patients.

What evidence suggests that this trial's treatments could be effective for Kaposi sarcoma?

Research has shown that using pomalidomide with liposomal doxorubicin may effectively treat Kaposi sarcoma (KS). In this trial, participants will receive this combination at either escalating doses or the highest tolerated dose, depending on the study group. Studies have found that pomalidomide is a safe and effective treatment for KS, even for people with HIV. One study showed that this drug combination resulted in better response rates and fewer side effects compared to traditional chemotherapy. Early results suggest that the treatment can shrink KS lesions. This combination specifically targets cancer cells while sparing healthy ones, potentially increasing effectiveness and reducing side effects. ^{1 2 3 5 6}

Who Is on the Research Team?

Ramya M Ramaswami, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults with Kaposi sarcoma (KS), including those with HIV. Participants must have confirmed KS, measurable lesions or assessable disease, and normal organ/marrow function. They should not have had certain treatments that would affect lesion assessment and must be willing to follow specific safety programs like POMALYST REMS if taking pomalidomide.

Inclusion Criteria

All HIV+ patients must be willing to be compliant with HAART

All study participants must agree to be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program

My Kaposi's sarcoma didn't respond well to chemotherapy.

Exclusion Criteria

You are taking any other experimental drugs.

You have had allergic reactions to certain medications similar to the one being studied.

I have a type of cancer that is not skin cancer, cervical, or anal dysplasia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pomalidomide and liposomal doxorubicin in 4-week cycles, with Doxil administered via IV on Day 1 and pomalidomide tablets taken daily for the first 3 weeks of each cycle.

Ongoing until optimal tumor response or unacceptable toxicity

Visits before starting treatment, to start each cycle, and on Day 15 of the first 2 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits for up to 5 years.

Up to 5 years

Several follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Liposomal Doxorubicin
• Pomalidomide

Trial Overview The study tests a drug combo for treating KS: IV liposomal doxorubicin on day one of each cycle and daily oral pomalidomide tablets for the first three weeks of each cycle. Treatment continues as long as it's tolerated and effective, with regular monitoring up to five years post-treatment.

How Is the Trial Designed?

Group I: 4/Group II; Antitumor Assessment Phase Experimental Treatment 2 Interventions

Pomalidomide and liposomal doxorubicin, given at the highest tolerated dose to patients with KS or KS with concurrent KSHV-associated MCD or KICS requiring systemic therapy

Group II: 3/Group II Experimental Treatment 2 Interventions

Pomalidomide with liposomal doxorubicin given at escalating doses in to patients with advanced KS or KS and concurrent KSHV-associated MCD or KICS requiring systemic therapy

Group III: 2/Group I; Antitumor Assessment Phase Experimental Treatment 2 Interventions

Pomalidomide and liposomal doxorubicin, given at the highest tolerated dose to patients with KS requiring systemic therapy

Group IV: 1/Group I Experimental Treatment 2 Interventions

Pomalidomide and liposomal doxorubicin given at escalating doses to patients with KS requiring systemic therapy

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

Approved in European Union as Caelyx for:

• Ovarian cancer
• Breast cancer
• Kaposi's sarcoma
• Multiple myeloma

Approved in United States as Doxil for:

• Ovarian cancer
• Breast cancer
• Kaposi's sarcoma
• Multiple myeloma

Approved in Canada as Caelyx for:

• Ovarian cancer
• Breast cancer
• Kaposi's sarcoma

Approved in Japan as Caelyx for:

• Ovarian cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pegylated liposomal doxorubicin (PLD) and daunorubicin citrate liposome (DNX) show higher response rates and less toxicity compared to conventional chemotherapy regimens for advanced Kaposi's sarcoma, making them more effective treatment options.

Patients treated with PLD or DNX experienced improved health-related quality of life in several areas, despite some common side effects like myelosuppression and stomatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of liposomal anthracyclines in Kaposi's sarcoma. Krown, SE., Northfelt, DW., Osoba, D., et al.[2019]

Pegylated liposomal doxorubicin (PLD) is an effective treatment for ovarian cancer that significantly reduces the risk of cardiotoxicity and other common side effects like nausea and hair loss, thanks to its unique formulation.

However, PLD is associated with dose-limiting cutaneous toxicities, including hand-foot syndrome, follicular rash, intertrigo-like eruptions, and hyperpigmentation, which are important considerations for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (PLD): enhanced skin toxicity in areas of vitiligo. Yuan, Y., Orlow, SJ., Curtin, J., et al.[2022]

Pegylated liposomal doxorubicin (Caelyx®/Doxil®) is an improved formulation of conventional doxorubicin that significantly reduces cardiotoxicity and enhances pharmacokinetics.

Clinical trials demonstrate that pegylated liposomal doxorubicin is effective in treating several cancers, including metastatic breast cancer and ovarian cancer, while maintaining a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin: a guide to its use in various malignancies. Lyseng-Williamson, KA., Duggan, ST., Keating, GM.[2018]

Caelyx/Doxil, a pegylated liposomal formulation of doxorubicin, has a unique pharmacokinetic profile that allows it to effectively target tumor sites while reducing toxicity compared to traditional doxorubicin.

It has been approved by the FDA and EMEA for treating AIDS-related Kaposi's sarcoma and recurrent epithelial ovarian cancer, and is being investigated for use in various other cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Tejada-Berges, T., Granai, CO., Gordinier, M., et al.[2022]

Liposomal doxorubicin was effective in treating Kaposi's sarcoma in HIV-infected patients, with five out of eight participants achieving a complete clinical response and three showing a partial response after six months of treatment.

While the treatment led to significant improvements, all patients experienced relapse after stopping therapy, highlighting the need for ongoing treatment; however, neutropenia was managed successfully with filgrastim, allowing for uninterrupted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Kaposi's sarcoma with liposomal doxorubicin. Bergin, C., O'Leary, A., McCreary, C., et al.[2019]

In a Phase I/II study involving 15 patients with HIV-related cutaneous Kaposi's sarcoma, Doxil (liposomal doxorubicin) demonstrated a high partial response rate of 73%, indicating its efficacy as a palliative treatment for this severe condition.

Doxil was well tolerated among patients, with manageable toxicity primarily affecting blood cell counts, suggesting it is a safer option for patients with poor prognosis who have previously undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS. James, ND., Coker, RJ., Tomlinson, D., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02659930

Pomalidomide in Combination With Liposomal Doxorubicin ... To preliminarily evaluate the antitumor effect of pomalidomide in combination with liposomal doxorubicin against Kaposi sarcoma. Eligibility: Patients with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.11552

A phase I trial of pomalidomide in combination with ... A phase I trial of pomalidomide in combination with liposomal doxorubicin in patients with Kaposi sarcoma with or without other KSHV-associated diseases.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8898289/

Safety, activity, and long-term outcomes of pomalidomide in ... Pomalidomide is a safe and active chemotherapy-sparing agent for the treatment of KS among individuals with or without HIV.

4. withpower.com withpower.com/trial/phase-1-sarcoma-2016-c40e2

Pomalidomide + Liposomal Doxorubicin for Kaposi Sarcoma Pegylated liposomal doxorubicin (PLD) and daunorubicin citrate liposome (DNX) show higher response rates and less toxicity compared to conventional chemotherapy ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/jmv.70294

Modern Approach to Manage Patients With Kaposi Sarcoma Of note, a Phase I study explored the effect of pomalidomide associated with liposomal doxorubicin in KS patients, with a partial response rate ...

6. blogs.the-hospitalist.org blogs.the-hospitalist.org/content/doxorubicin-pomalidomide-combo-shows-promise-kaposi-sarcoma

Doxorubicin-pomalidomide combo shows promise for ... Liposomal doxorubicin (Dox) plus pomalidomide (Pom) was safe and active in heavily pretreated patients with Kaposi sarcoma, according to results ...