Chemotherapy and Radiation for Cutaneous Angiosarcoma

Overseen by Anthony Apicelli, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Washington University School of Medicine

Must be taking: Paclitaxel

Must not be taking: Investigational agents

Disqualifiers: Other malignancy, CNS disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Angiosarcoma is a rare and aggressive form of soft tissue sarcoma. Prior work demonstrates very poor outcomes, with most patients developing metastatic disease and less than 50% surviving greater than 5 years. In other soft tissue sarcomas, the use of radiotherapy and/or chemotherapy have improved progression-free survival in patients undergoing limited, organ-sparing surgeries. Taxane chemotherapy has shown efficacy in patients with metastatic angiosarcoma, but this has not been tested in patients with localized disease. This study examines the efficacy of induction paclitaxel followed by concurrent chemoradiation therapy with paclitaxel prior to curative surgical resection.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications, but you must be receiving or planning to receive weekly paclitaxel treatment. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment for cutaneous angiosarcoma?

Research shows that using paclitaxel with radiation therapy improves survival rates for patients with cutaneous angiosarcoma compared to other treatments. Patients treated with this combination had better overall survival and progression-free survival. ^{1 2 3 4 5}

Is the combination of paclitaxel and radiation therapy generally safe for humans?

Paclitaxel, used in combination with radiation therapy, has been studied for safety in treating cutaneous angiosarcoma. Adverse events were observed in 69.1% of cases, with peripheral neuropathy (nerve damage) occurring only in the paclitaxel-treated group. However, the treatment is considered tolerable for maintenance therapy in the Japanese population. ^{1 2 3 6 7}

How is the treatment of paclitaxel and radiation therapy unique for cutaneous angiosarcoma?

The combination of paclitaxel (a chemotherapy drug) and radiation therapy is unique for treating cutaneous angiosarcoma because it has shown better survival outcomes compared to conventional surgery, and it is now considered a standard treatment for this rare and aggressive cancer. ^{1 2 3 5 8}

Research Team

Anthony Apicelli, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with measurable cutaneous angiosarcoma, a rare skin cancer. They must be fit enough for treatment (ECOG ≤1), agree to use contraception, and not have other recent cancers except certain skin cancers or cervical carcinoma in situ. Participants need to start radiotherapy within the first 7 weeks of weekly paclitaxel chemotherapy.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)

I am starting or already on a weekly paclitaxel treatment and can start radiotherapy within 7 weeks of it.

Exclusion Criteria

I haven't had cancer, except for certain skin cancers or cervical pre-cancer, in the last 3 years.

I am HIV-positive with a CD4+ T-cell count below 350.

I do not have brain metastases or central nervous system disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive 6 weekly cycles of paclitaxel at 80 mg/m^2 as induction chemotherapy

6 weeks

Concurrent Chemoradiation

Participants receive 6 weekly cycles of paclitaxel at 80 mg/m^2 concurrently with radiation therapy (50.4 Gy in 28 fractions over 7 weeks)

7 weeks

Surgery

Standard of care surgery ideally within 6 weeks after completing concurrent chemotherapy and radiation therapy

6 weeks

Follow-up

Participants are monitored for overall survival and progression-free survival

2 years and 12 weeks

Treatment Details

Interventions

• Paclitaxel (Anti-microtubule agent)
• Radiation therapy (Radiation)
• Research blood draw (Procedure)

Trial Overview The study tests induction paclitaxel followed by concurrent chemoradiation therapy before surgical removal of the tumor. It aims to see if this approach improves outcomes in patients with localized disease who are typically treated with surgery alone.

Participant Groups

Group I: Paclitaxel and Radiation Experimental Treatment 3 Interventions

* All patients will receive standard of care induction chemotherapy with 6 weekly cycles of paclitaxel at 80 mg/m\^2. They will then receive 6 weekly cycles of paclitaxel at 80 mg/m\^2 concurrently with radiation therapy. Patients will be receiving paclitaxel as part of their routine care, but in order to participate in this study, their induction chemotherapy regimen must be paclitaxel. Radiation therapy is 50.4 Gy in 28 fractions delivered within 7 weeks. A radiation therapy boost of 10-16.2 Gy over 5-9 fractions is allowed at the discretion of the treating physician. * Standard of care surgery ideally within 6 weeks after completing concurrent chemotherapy and radiation therapy

Paclitaxel is already approved in Canada for the following indications:

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Findings from Research

In a retrospective study of 21 cases of cutaneous angiosarcoma (CAS), patients treated with paclitaxel combined with radiotherapy (PTX + RT) followed by maintenance chemotherapy had significantly better overall survival (28 months) and progression-free survival (12 months) compared to other treatments (10 months OS and 5 months PFS).

The findings support the use of PTX + RT followed by maintenance taxane chemotherapy as a superior treatment option for CAS, reinforcing previous research that indicated this approach is more effective than conventional surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a combination of paclitaxel and radiation therapy against cutaneous angiosarcoma: A single-institution retrospective study of 21 cases. Seo, T., Kitamura, S., Yanagi, T., et al.[2022]

In a study of 90 Japanese patients with cutaneous angiosarcoma, docetaxel showed equivalent overall survival and treatment duration compared to paclitaxel, suggesting it is a viable alternative for maintenance therapy.

While both treatments had adverse events, docetaxel was associated with a higher incidence of severe side effects (40.0%) compared to paclitaxel (23.6%), indicating a need for careful monitoring when using docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous angiosarcoma treated with taxane-based chemoradiotherapy: A multicenter study of 90 Japanese cases. Fujimura, T., Furudate, S., Maekawa, T., et al.[2023]

Patients with cutaneous angiosarcoma receiving concurrent paclitaxel-based chemoradiotherapy (CRT) showed a significantly higher 2-year overall survival rate of 94.1% compared to 71.6% in those receiving other treatments, indicating the efficacy of CRT.

Despite no significant differences in local control, distant control, or progression-free survival between CRT and non-CRT groups, the promising overall survival results warrant further investigation in a prospective phase 2 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel and radiation therapy for the treatment of cutaneous angiosarcoma. Roy, A., Gabani, P., Davis, EJ., et al.[2022]

In a study of 50 Japanese patients with taxane-resistant cutaneous angiosarcoma (CAS), switching between taxanes (paclitaxel and docetaxel) showed a better safety profile compared to eribulin methylate and pazopanib, with fewer adverse events reported.

Although there was no significant difference in progression-free survival among the treatment regimens, the taxane-switch group experienced significantly lower rates of severe adverse events, suggesting it may be a safer option for second-line therapy in CAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment for taxane-resistant cutaneous angiosarcoma: A multicenter study of 50 Japanese cases. Fujimura, T., Maekawa, T., Kato, H., et al.[2023]

A woman with non-small cell lung cancer developed a photodistributed dermatitis as a side effect of nab-paclitaxel therapy, which worsened with each treatment cycle, highlighting the potential for skin reactions in patients receiving taxane chemotherapy.

The patient's condition improved with topical corticosteroids and strict sun avoidance, indicating that while photodermatoses can occur with taxane treatments, they can be managed effectively without necessarily stopping chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel-associated photosensitivity: report in a woman with non-small cell lung cancer and review of taxane-related photodermatoses. Beutler, BD., Cohen, PR.[2020]

In a study of 25 patients with advanced cutaneous angiosarcoma (CAS) who had previously been treated with taxanes, eribulin mesylate demonstrated a median overall survival of 8.6 months and a response rate of 20%, suggesting it may be a viable second-line treatment option.

Despite the promising efficacy, caution is advised due to the occurrence of severe adverse events in over half of the participants, although all patients recovered, indicating a need for careful monitoring, especially in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of eribulin mesylate for patients with cutaneous angiosarcoma previously treated with taxane: a multicentre prospective observational study. Fujisawa, Y., Fujimura, T., Matsushita, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of a combination of paclitaxel and radiation therapy against cutaneous angiosarcoma: A single-institution retrospective study of 21 cases. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Cutaneous angiosarcoma treated with taxane-based chemoradiotherapy: A multicenter study of 90 Japanese cases. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel and radiation therapy for the treatment of cutaneous angiosarcoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Single institutional experience of radiation therapy for angiosarcoma of the scalp without cervical lymph node metastases: Impact of concurrent chemoradiation with maintenance chemotherapy using taxanes on patient prognosis. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Management of Cutaneous Angiosarcoma: an Update Review. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Treatment for taxane-resistant cutaneous angiosarcoma: A multicenter study of 50 Japanese cases. [2023]

7. Austria pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel-associated photosensitivity: report in a woman with non-small cell lung cancer and review of taxane-related photodermatoses. [2020]

8. England pubmed.ncbi.nlm.nih.gov

The efficacy of eribulin mesylate for patients with cutaneous angiosarcoma previously treated with taxane: a multicentre prospective observational study. [2022]