Chemotherapy + Radiation for Soft Tissue Sarcoma

Not currently recruiting at 434 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining the drug pazopanib with chemotherapy and radiation therapy for treating non-rhabdomyosarcoma soft tissue sarcomas that can be surgically removed. It explores whether this combination is more effective than radiation alone. Individuals recently diagnosed with a soft tissue sarcoma in the arms, legs, or trunk, and whose tumors are potentially removable, might be suitable candidates. The trial aims to determine if these combined treatments can effectively halt tumor growth and spread. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that pazopanib is generally safe for patients with advanced soft tissue sarcomas, especially after chemotherapy. The FDA has approved it for this use, indicating a well-understood safety profile. However, limited information exists about its use with radiation or chemotherapy.

When doxorubicin and ifosfamide are combined with radiation therapy, studies have found this approach can be intense. Patients might experience increased side effects, such as nausea, fatigue, and low blood cell counts. Despite these risks, these drugs are often used and are considered safe for treating soft tissue sarcomas.

Overall, while each treatment has its own side effects, they are usually manageable. Discussing potential risks and benefits with a healthcare provider is important before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for soft tissue sarcoma because they explore different combinations of chemotherapy, radiation, and the drug pazopanib. Unlike the standard care that typically involves chemotherapy drugs like doxorubicin and ifosfamide along with radiation, Regimen C introduces pazopanib, a targeted therapy that may enhance the effects of radiation. Regimen A combines pazopanib with chemoradiation, potentially offering a more powerful approach compared to traditional methods. Regimen D focuses solely on radiation, which could optimize treatment for patients unable to tolerate chemotherapy. Each regimen provides unique potential benefits over the standard treatments, offering hope for more effective management of soft tissue sarcoma.

What evidence suggests that this trial's treatments could be effective for non-rhabdomyosarcoma soft tissue sarcomas?

Research has shown that pazopanib, included in Regimen A and Regimen C of this trial, may help treat soft tissue sarcomas. In some studies, it prolonged the time before cancer worsened compared to a placebo. Approximately 46.3% of patients with certain sarcomas experienced tumor shrinkage or halted growth.

Doxorubicin and ifosfamide, part of Regimen B, are chemotherapy drugs effective for soft tissue sarcomas. They have a response rate of about 20% to 34%, indicating they can shrink tumors or slow their growth in many cases. Radiation therapy, used in Regimen C, Regimen D, and as part of chemoradiation in Regimen A and Regimen B, uses high-energy rays to kill cancer cells. Together, these treatments offer a comprehensive approach to addressing soft tissue sarcomas in this trial. ^{6 7 8 9 10}

Who Is on the Research Team?

Aaron R Weiss

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

My doctor expects me to live at least 3 more months with treatment.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1.

acsjournals.onlinelibrary.wiley.com

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

Chemotherapy for soft tissue sarcoma - Ratan - 2016 - Cancer

Despite 2 recent drug approvals, doxorubicin and ifosfamide remain the most effective chemotherapy drugs available for the treatment of majority of these ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/8453706/

Efficacy of ifosfamide in combination with doxorubicin for ...

Of the 279 adults with soft-tissue sarcoma who were entered in the study, 260 were analyzed. The overall response rate was 20% for doxorubicin, 34% for ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1278321815003777

Effective local control of advanced soft tissue sarcoma with ...

Our five-year data on the feasibility and effectiveness of neoadjuvant chemoradiotherapy with systemically effective doses of adriamycin and ifosfamide combined ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e23529

The role of ifosfamide-doxorubicin chemotherapy in ...

Ifosfamide-Doxorubicin chemotherapy benefits younger patients with > 5cm, high grade, STS of the trunk or extremity, with histologies of Synovial Cell, DDL, ...

5.

ccjm.org

ccjm.org/content/ccjom/77/3_suppl_1/S23.full.pdf

Use of chemotherapy for patients with bone and soft-tissue ...

Drugs found to have activity against metastatic sarcoma include doxorubicin, ifosfamide, platinum agents, gem- citabine, taxanes, and dacarbazine. Used either ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12524033/

Reporting Matters: Severe Adverse Events in Soft Tissue ...

Intensified adjuvant IFADIC chemotherapy in combination with radiotherapy versus radiotherapy alone for soft tissue sarcoma: long-term ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00334854?tab=table

Ifosfamide and Doxorubicin, Radiation Therapy, and/or ...

Ifosfamide and Doxorubicin, Radiation Therapy, and/​or Surgery in Treating Young Patients With Localized Soft Tissue Sarcoma.

8.

emedicine.medscape.com

emedicine.medscape.com/article/2007168-overview

Soft Tissue Sarcoma Treatment Protocols

Combination chemotherapy recommendations for metastatic disease · Doxorubicin 20-25 mg/m2 IV push on days 1-3 plus · Ifosfamide 2000-3000 mg/m2 IV ...

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11987756/

The Decline and Fall of the Current Chemotherapy ...

Chemotherapy remains an inadequate treatment option for soft tissue sarcoma, and novel therapies are needed.

10.

frontiersin.org

frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.762288/full

Doxorubicin/Adriamycin Monotherapy or Plus Ifosfamide in ...

In this study, we conducted a pooled analysis to comprehensively compare the efficacy and tolerability between AI and ADM in patients with previously untreated ...