Chemotherapy + Radiation for Soft Tissue Sarcoma

Recruiting at 415 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 substrates, inhibitors, inducers

Disqualifiers: CNS metastases, Uncontrolled hypertension, 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: 7

140 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether a new drug called pazopanib, when combined with chemotherapy and radiation, works better for patients with a specific type of soft tissue cancer. Pazopanib helps stop cancer cells from growing, while chemotherapy and radiation kill the cells. The goal is to see if this combination can improve treatment outcomes.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking certain medications that affect the liver enzyme CYP3A4, you may need to stop them before joining the trial. It's best to discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the treatment for soft tissue sarcoma?

Research shows that doxorubicin, often combined with ifosfamide, is a standard treatment for advanced soft tissue sarcoma, with some studies indicating improved survival rates when used in combination with other drugs. However, these combinations can lead to increased side effects. Radiation therapy is also a common part of treatment, especially in combination with surgery, to help control the disease. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiation therapy safe for treating soft tissue sarcoma?

Doxorubicin, a common chemotherapy drug used for soft tissue sarcoma, can cause heart-related side effects, known as cardiotoxicity. Ifosfamide, another chemotherapy drug, can cause bladder issues, but these can be managed with a protective agent called mesna. Liposomal doxorubicin, a modified form of doxorubicin, has fewer acute and chronic toxicities, making it potentially safer. ^{3 6 7 8 9}

What makes the chemotherapy and radiation treatment for soft tissue sarcoma unique?

This treatment combines doxorubicin and radiation therapy, which has shown a synergistic effect, meaning they work better together than alone, leading to a high response rate in patients with advanced soft tissue sarcomas. It is administered on an outpatient basis with low toxicity, making it a promising option for those with advanced stages of the disease. ^{1 6 10 11 12}

Research Team

Aaron R Weiss

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can be surgically removed. Eligible participants include those with various types of sarcoma, adequate organ function, and no metastases to the central nervous system. They must be able to swallow tablets, have a life expectancy of at least 3 months, and not have received certain prior treatments.

Inclusion Criteria

My sarcoma is not classified under specific types.

Your heart is pumping normally, with a strong enough squeeze.

I am on blood thinners with a stable INR.

Exclusion Criteria

I do not have any current bleeding or conditions that cause excessive bleeding.

I had surgery to completely remove my tumor before joining ARST1321.

My high blood pressure is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive pazopanib and undergo radiation therapy, with or without chemotherapy, to prepare for surgery

10-13 weeks

Weekly visits for treatment administration

Surgery

Patients undergo surgery to remove the tumor

1 week

1 visit (in-person)

Continuation

Patients continue to receive pazopanib and possibly additional radiation therapy

12 weeks

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Follow-up visits at 6, 12, 18, 24, 30, 36, 48, and 60 months

Treatment Details

Interventions

• Doxorubicin
• Ifosfamide
• Pazopanib
• Radiation Therapy

Trial Overview The study is testing whether pazopanib combined with chemotherapy (ifosfamide and doxorubicin) and radiation therapy works better than radiation alone in treating these sarcomas before surgery. Pazopanib blocks enzymes needed for tumor growth while chemotherapy kills or stops cancer cells from dividing.

Participant Groups

Group I: Regimen D (radiation therapy) Experimental Treatment 2 Interventions

INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.

Group II: Regimen C (pazopanib, radiation therapy) Experimental Treatment 4 Interventions

INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.

Group III: Regimen B (chemoradiation) Experimental Treatment 5 Interventions

See Regimen B Detailed Description.

Group IV: Regimen A (pazopanib, chemoradiation) Experimental Treatment 7 Interventions

See Regimen A Detailed Description.

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

Approved in United States as Adriamycin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in European Union as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Canada as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Japan as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Doxorubicin (ADR) and ifosfamide have shown single-agent response rates above 20% in advanced soft tissue sarcoma, but the overall role of chemotherapy in these cases remains controversial.

Combination therapies like ADR + DTIC and CYVADIC have higher response rates, yet most studies indicate no significant survival benefit from chemotherapy compared to control groups, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for soft tissue sarcoma--current concepts and review]. Umeda, T., Ishii, T., Hatakeyama, K., et al.[2013]

In a phase II study involving 16 patients with recurrent or metastatic soft tissue sarcomas, liposomal doxorubicin (Doxil) showed no significant responses, indicating limited efficacy in this specific patient population.

Despite the lack of effectiveness, Doxil was well tolerated, with no grade 4 toxicities and only a few instances of grade 3 toxicities, suggesting a favorable safety profile for future studies in different patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of Doxil (liposomal doxorubicin): lack of activity in poor prognosis soft tissue sarcomas. Garcia, AA., Kempf, RA., Rogers, M., et al.[2022]

In a study of 504 patients with soft-tissue sarcomas receiving doxorubicin, the incidence of significant cardiotoxicity was low, even at high cumulative doses (>450 mg/m2), suggesting that doxorubicin can be safely administered with careful monitoring.

The use of the cardioprotectant dexrazoxane did not impact the efficacy of doxorubicin treatment, indicating that it can be an effective strategy to mitigate cardiotoxic risks without compromising cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of Doxorubicin Cardiotoxicity in Patients with Advanced Soft-tissue Sarcoma Treated in the ANNOUNCE Phase III Randomized Trial. Jones, RL., Wagner, AJ., Kawai, A., et al.[2022]

Doxorubicin, a common chemotherapy drug, shows limited survival benefits for patients with localized or metastatic soft tissue sarcoma, despite causing some tumor responses.

Activation of the insulin-like growth factor-I receptor (IGF-I-R) in sarcoma cells can lead to resistance against doxorubicin, suggesting that targeting IGF-I-R may improve the effectiveness of chemotherapy in treating soft tissue sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin-like growth factor-I receptor activation blocks doxorubicin cytotoxicity in sarcoma cells. Beech, DJ., Perer, E., Helms, J., et al.[2014]

The IVADo regimen, which combines doxorubicin with ifosfamide, vincristine, and actinomycin D, showed a 76% response rate in treating pediatric soft tissue sarcoma, indicating its efficacy in reducing tumor volume.

While the treatment was effective, it also resulted in significant toxicity, particularly myelosuppression, with 67% of cycles causing Grade 4 neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IVADo regimen--a pilot study with ifosfamide, vincristine, actinomycin D, and doxorubicin in children with metastatic soft tissue sarcoma: a pilot study of behalf of the European pediatric Soft tissue sarcoma Study Group. Bisogno, G., Ferrari, A., Bergeron, C., et al.[2022]

References

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

Getting up-to-date in the management of soft tissue sarcoma. [2018]

2. Egypt pubmed.ncbi.nlm.nih.gov

Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Ifosfamide in the adjuvant therapy of soft tissue sarcomas. [2017]

4. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for soft tissue sarcoma--current concepts and review]. [2013]

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

Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity. [2019]

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

A phase II study of Doxil (liposomal doxorubicin): lack of activity in poor prognosis soft tissue sarcomas. [2022]

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

Prospective Evaluation of Doxorubicin Cardiotoxicity in Patients with Advanced Soft-tissue Sarcoma Treated in the ANNOUNCE Phase III Randomized Trial. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Insulin-like growth factor-I receptor activation blocks doxorubicin cytotoxicity in sarcoma cells. [2014]

9. Egypt pubmed.ncbi.nlm.nih.gov

Phase II Clinical Trial With Pegylated Liposomal Doxorubicin (CAELYX(R)/Doxil(R)) and Quality of Life Evaluation (EORTC QLQ-C30) in Adult Patients With Advanced Soft Tissue Sarcomas: A study of the Spanish Group for Research in Sarcomas (GEIS). [2022]

10. Greece pubmed.ncbi.nlm.nih.gov

Concomitant chemo-radiotherapy in the treatment of locally advanced and/or metastatic soft tissue sarcomas: experience of the National Cancer Institute of Genoa. [2013]

11. Ireland pubmed.ncbi.nlm.nih.gov

The treatment of soft tissue sarcomas with focus on chemotherapy: a review. [2019]

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

The IVADo regimen--a pilot study with ifosfamide, vincristine, actinomycin D, and doxorubicin in children with metastatic soft tissue sarcoma: a pilot study of behalf of the European pediatric Soft tissue sarcoma Study Group. [2022]