Doxil + Doxorubicin for Soft Tissue Sarcoma

Overseen By Margaret von Mehren, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Fox Chase Cancer Center

Must be taking: Doxorubicin, Doxil

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Breastfeeding, Other active cancer, others

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

Compensation: Varies

Number of Visits: 24

Duration: Varies based on individual response

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a specific biomarker can predict the response of people with soft tissue sarcoma to doxorubicin or Doxil, both chemotherapy drugs. Participants will receive either doxorubicin every 21 days or Doxil every 28 days, and doctors will assess the cancer's response after every two cycles. The trial is open to individuals with specific types of soft tissue sarcoma who plan to start treatment with these drugs, with or without the additional drug olaratumab. It may suit those with certain sarcoma subtypes who are about to begin chemotherapy with these agents. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational agents, chemotherapy, radiation, or hormonal therapy, except for olaratumab.

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

Research has shown that both Doxil and doxorubicin are generally well-tolerated, though they carry some risks. Doxil, a form of doxorubicin, is considered safer than older versions, typically having less impact on the heart and causing fewer blood-related side effects. However, it can still lead to side effects like nausea and fatigue.

Doxorubicin is effective but also poses risks. In large amounts over time, it can cause heart problems. Some individuals may experience skin and eye irritation. Following the safety instructions provided by healthcare providers is crucial when using these drugs.

Both drugs have been widely studied and received FDA approval for treating certain cancers, indicating strong evidence of their safety when used as directed. However, like any treatment, side effects can occur, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for soft tissue sarcoma, which include surgery, radiation, and chemotherapy, Doxil and Doxorubicin are being explored for their potential to enhance treatment effectiveness through a specific biomarker, TOPO2A. This biomarker may help identify which patients are more likely to respond well to these drugs, allowing for a more personalized treatment approach. Researchers are excited about this because it could lead to better-targeted therapies, minimizing unnecessary side effects and improving outcomes for patients with soft tissue sarcoma.

What evidence suggests that this trial's treatments could be effective for sensitivity to doxorubicin or its derivatives?

Research has shown that doxorubicin treats soft tissue sarcoma by stopping cancer cells from growing and spreading. Studies have found that patients with sarcoma can safely handle high doses of doxorubicin, which is crucial for its effectiveness. In this trial, participants will receive either doxorubicin or Doxil, a version of doxorubicin. Doxil offers the same cancer-fighting benefits but with fewer heart-related side effects, making it a potentially safer choice for patients concerned about heart issues. Both treatments have also proven effective in other types of cancer, suggesting they could work well for soft tissue sarcomas too. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Inclusion Criteria

Patients must consent to providing tumor tissue prior to initiation of therapy if sufficient archival tissue is not available. Archival tissue is permitted if no other anticancer treatment was given after the tissue was obtained (not including surgery or radiation). If a biopsy is required, the treating physician should ensure that this can be done safely.

Patients with STS will be eligible for the trial if their next planned chemotherapy will include single agent doxorubicin or doxil. Patients who will be receiving concomitant therapy with olaratumab will be allowed to participate.

Sarcoma subtypes of angiosarcoma, epithelioid sarcoma, leiomyosarcoma, fibrosarcoma, myxofibrosarcoma, synovial sarcoma, pleomorphic rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, liposarcoma (excluding well-differentiated) and malignant peripheral nerve sheath tumor will be included. These are subtypes for which a targeted therapy is not standard of care. All other subtypes will be included on a case by case basis as determined by the principle investigator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxorubicin or Doxil at standard intervals until disease progression, prohibitive toxicity, or completion of cumulative dose

Varies based on individual response

Every 21 days for doxorubicin, every 28 days for Doxil

Follow-up

Participants are monitored for overall survival and best response using RECIST criteria

6 years

Every 3 months for 1 year, every 6 months in year 2, annually thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Doxil
• Doxorubicin

How Is the Trial Designed?

Group I: Doxorubicin Experimental Treatment 1 Intervention

Group II: Doxil Experimental Treatment 1 Intervention

Doxil is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Doxil for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Approved in European Union as Caelyx for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma
• Breast cancer

Approved in Canada as Doxorubicin liposomal for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10054554/

Recent Preclinical and Clinical Progress in Liposomal ...

Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin ...

2.

bmjoncology.bmj.com

bmjoncology.bmj.com/content/4/1/e000573

Thirty years from FDA approval of pegylated liposomal ...

Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus ...

3.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/caelyx-pegylated-liposomal

Caelyx pegylated liposomal - European Medicines Agency

For metastatic breast cancer, in a study involving 509 women, Caelyx pegylated liposomal was as effective as standard doxorubicin: the time until the disease ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S092375341964144X

Reduced cardiotoxicity and comparable efficacy in a phase ...

In first-line therapy for MBC,PLD provides comparable efficacy to doxorubicin, with significantly reducedcardiotoxicity, myelosuppression, vomiting andalopecia.

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00103506

NCT00103506 | Study of DOXIL/CAELYX (Pegylated ...

The purpose of this study is to evaluate time to progression, overall survival, response rate and safety for the two open-label treatment groups; DOXIL/CAELYX ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2022/050718Orig1s060lbl.pdf

DOXIL (LIPOSOMAL) [DOXORUBICIN HYDROCHLORIDE ...

The safety data reflect exposure to doxorubicin hydrochloride liposome injection in 1310 patients including: 239 patients with ovarian cancer, 753 patients ...

7.

imgcdn.mckesson.com

imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9SUNPH_DOXORUBICIN_LIPOSOME_SDV_2MG_ML_25ML.pdf

MATERIAL SAFETY DATA SHEET

Doxorubicin Hydrochloride is a known carcinogen in animals and a probable carcinogen in humans. This drug is intended for human pharmaceutical use by.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3514106/

Comparison of safety and toxicity of liposomal doxorubicin vs ...

Liposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression.

9.

ema.europa.eu

ema.europa.eu/en/documents/product-information/myocet-liposomal-epar-product-information_en.pdf

Myocet liposomal, INN-doxorubicin

Data from randomised controlled clinical trials show that the efficacy and cardiac safety of Myocet liposomal in this population was comparable to that observed ...

10.

baxter.com

baxter.com/doxil-doxorubicin-hcl-liposome-injection-hospital-care

Doxil (doxorubicin HCl liposome injection) for Hospital Care

Embryo-Fetal Toxicity: Based on animal data, DOXIL liposomal infusion can cause fetal harm when administered to a pregnant woman; avoid the use of DOXIL ...