Doxorubicin for Soft Tissue Sarcoma

Overseen By Katharine Russman

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Investigational agents

Disqualifiers: Prior anthracycline, Immune deficiency, CNS metastases, 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

Compensation: Varies

Number of Visits: 15

Duration: 24 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a different dosing schedule of doxorubicin, a common cancer medicine, to determine its effectiveness for older patients with inoperable soft tissue leiomyosarcoma. The goal is to assess whether administering lower doses more frequently can slow the cancer and reduce side effects. Researchers will also evaluate the treatment's impact on patients' quality of life and immune system. This trial may suit individuals aged 65 and older with leiomyosarcoma that cannot be surgically removed and who have not previously received doxorubicin. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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. However, you cannot be on other investigational agents or have had recent chemotherapy, targeted therapy, or radiation therapy within 21 days before starting the trial.

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

Studies have shown that doxorubicin is generally well-tolerated, although side effects can occur. An initial study found that when doxorubicin was combined with another drug, the side effects were manageable for most patients. However, patients with advanced sarcoma reported a decline in quality of life during doxorubicin treatment. This suggests that while the drug can be effective, it may also cause discomfort or other issues.

Doxorubicin is a common treatment for soft tissue sarcoma, and doctors are familiar with its safety and how to manage any side effects. This trial aims to use a lower dose on a weekly schedule, which might reduce side effects while still effectively fighting the cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Doxorubicin is unique because it targets soft tissue sarcoma with a bolus infusion method, which is less common in current treatments. This approach allows for precise dosing on specific days, potentially improving effectiveness while minimizing side effects. Additionally, the use of dexrazoxane for cardioprotection and pegfilgrastim for growth factor support makes it stand out by addressing common treatment concerns like heart damage and low blood cell counts. Researchers are excited about these features as they could enhance patient safety and treatment outcomes.

What evidence suggests that this treatment might be an effective treatment for leiomyosarcoma?

Research has shown that doxorubicin, a common chemotherapy drug, can help treat soft tissue sarcoma, a type of cancer. Studies have found that patients with advanced soft tissue sarcoma live about 14 to 19 months on average when treated with doxorubicin. The overall response rate, indicating how many patients experience a reduction in tumor size, ranges from about 20% to 47%. Evidence also suggests that a lower dose of doxorubicin may still be effective and cause fewer side effects, particularly for older or frail patients. Additionally, using doxorubicin at lower doses might help boost the immune system, providing an extra benefit in fighting cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Breelyn Wilky, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for elderly patients aged 65-100 with advanced or metastatic leiomyosarcoma, a type of soft tissue sarcoma. It's specifically designed for those who cannot have their tumors surgically removed and are looking for an alternative treatment that may be easier to tolerate.

Inclusion Criteria

I am between 65 and 100 years old.

My organs are functioning well.

I am a male and agree to use contraception during and for 120 days after the study.

Exclusion Criteria

Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment, including NYHA Class II or greater heart disease

I have been treated with anthracycline before.

Hypersensitivity to doxorubicin or any excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxorubicin 25 mg/m2 administered by bolus with dexrazoxane pre-treatment on days 1 and 8 every 21 days for up to 8 cycles

24 weeks

Visits every 3 weeks for up to 8 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with scans for response imaging obtained every 12 weeks up to 1 year

12 months

Visits every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Doxorubicin

Trial Overview The study tests the effectiveness of a lower dose, weekly schedule of Doxorubicin in treating leiomyosarcoma. The main focus is on whether this regimen can control tumor growth without surgery over a period of 12 weeks while maintaining quality of life.

How Is the Trial Designed?

Group I: Doxorubicin Experimental Treatment 1 Intervention

Doxorubicin will be administered on days 1 and 8 every 21 days for a maximum of 8 cycles (Cycles 1-8) with appropriate premedications and pegfilgrastim growth factor support. Doxorubicin will be administered as a bolus infusion on day 1 and day 8 with dexrazoxane cardioprotection. Patients must have central line access for this protocol, including pheresis or trifusion catheter, PICC line, or port.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Cancer League of Colorado

Collaborator

Trials

13

Recruited

450+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5932429/

Outcome for Advanced or Metastatic Soft Tissue Sarcoma ... The median TTF was 4.7 months, and the median OS was 20.1 months. The overall response rate was 20%. Doses of doxorubicin monotherapy did not show significant ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e23552

Outcomes of metastatic synovial sarcoma with doxorubicin, ... Among the entire cohort the three-year OS rate was 78.9% (95%CI = 66.3-87.3) and five-year OS rate 68.7% (95%CI = 53.5-79.9).

3. clinicalsarcomaresearch.biomedcentral.com clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/s13569-020-00137-5

Survival of soft tissue sarcoma patients after completing six ... Overall survival (OS) with doxorubicin monotherapy is approximately 12.8 months and with doxorubicin/ifosfamide combination therapy ...

4. vivli.org vivli.org/correlation-of-doxorubicin-dose-and-survival-in-patients-with-soft-tissue-sarcoma-data-from-two-studies-a-larger-phase-iii-study-and-a-smaller-phase-ii-study-will-be-combined-and-analyzed/

Correlation of doxorubicin dose and survival in patients ... However, median survival in patients with newly diagnosed advanced soft tissue sarcoma is approximately 14-19 months with two-year survival rates of 20-30%.

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.30191

Chemotherapy for soft tissue sarcoma - Ratan - 2016 - Cancer The overall response rate was 47%, and 10% of patients achieved complete remission.19 The subsequent multicenter phase 3 results were reported ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9081717/

Quality of life of patients with soft tissue sarcoma treated ... Patients with advanced or metastatic sarcoma reported a relatively rapid decline in PROs during doxorubicin-based treatment.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.11519

A pilot study evaluating the safety, tolerability, and efficacy ... Conclusions: The combination of pembrolizumab with doxorubicin has manageable toxicity and preliminary promising activity in the treatment of ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9793899/

Efficacy and safety of sintilimab plus doxorubicin in ... Results: A total of 38 patients (20 men and 18 women) were enrolled in this study. The overall ORR was 39.5%, disease control rate was 71.1%, ...