Preoperative Chemotherapy + Surgery for Sarcoma

(STRASS2 Trial)

Recruiting at 159 trial locations

Overseen By EORTC HQ

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Must not be taking: Anthracyclines, Anthracenediones

Disqualifiers: Metastatic disease, Congestive heart failure, Uncontrolled hypertension, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 9-12 weeks

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding chemotherapy before surgery can improve outcomes for people with certain types of high-risk sarcoma, specifically dedifferentiated liposarcoma (a cancer that starts in fat cells) and leiomyosarcoma (a cancer that begins in smooth muscle tissue). Participants will be randomly assigned to one of two groups: one group will receive surgery alone, while the other will receive chemotherapy followed by surgery. The trial seeks individuals with a diagnosed high-risk sarcoma in the abdominal area who have tumors that can be surgically removed. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have uncontrolled high blood pressure, you may need to adjust your antihypertensive medication before joining the study. It's best to discuss your current medications with the trial team.

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

Research has shown that administering chemotherapy before surgery is generally safe for patients. Several studies have examined its effects on sarcoma, a type of cancer. One study found that pre-surgery chemotherapy was feasible and improved survival rates for some patients. Another study demonstrated that it reduced the likelihood of cancer recurrence in certain types of sarcoma.

However, not all studies agree on the benefits of this approach, as some did not find a clear improvement in outcomes. Despite this, the treatment's safety is considered acceptable, with a 4.5% chance of death within 30 days of treatment, similar to other treatments for this condition.

Overall, these studies suggest that preoperative chemotherapy is a reasonable option for treating sarcoma, with a safety level typical of cancer treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining preoperative chemotherapy with surgery for sarcoma because it offers a unique approach that could enhance treatment outcomes compared to surgery alone. Unlike traditional treatment, which typically involves surgery as a standalone procedure, this method uses chemotherapy before surgery to potentially shrink tumors, making them easier to remove and reducing the chance of cancer cells spreading. This approach could lead to improved survival rates and less invasive surgeries, offering new hope for patients battling sarcoma.

What evidence suggests that this trial's treatments could be effective for high risk DDLPS and LMS?

This trial will compare surgery alone with preoperative chemotherapy followed by surgery. Research has shown that administering chemotherapy before surgery can improve outcomes for patients with certain soft tissue sarcomas. In one study, 44% of patients who received this treatment remained disease-free five years later. Another study found that this approach helped prevent cancer recurrence in patients with aggressive sarcomas in the limbs. Although results can vary, evidence suggests that adding chemotherapy before surgery might reduce the risk of cancer returning and improve survival rates for individuals with high-risk sarcomas, such as dedifferentiated liposarcoma and leiomyosarcoma. ^{3 6 7 8 9}

Who Is on the Research Team?

Alessandro Gronchi

Principal Investigator

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Winan van Houdt

Principal Investigator

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Are You a Good Fit for This Trial?

This trial is for adults with high-risk leiomyosarcoma or liposarcoma in the retroperitoneal or pelvic spaces, who haven't had previous treatments. Tumors must be a certain size and meet specific criteria. Patients need to have good organ function, no severe illnesses, not be pregnant or breastfeeding, and agree to use effective birth control.

Inclusion Criteria

My diagnosis was confirmed with specific tests for MDM2 and CDK4.

I have a specific type of sarcoma (DDLPS) that is considered high risk but operable.

My LMS tumor is at least 5 cm in size.

Exclusion Criteria

You have certain types of sarcoma that originated from bone, abdominal or gynecological organs, and it has spread to other parts of the body. You have a history of severe allergic reactions to certain medications used to treat sarcoma. You have experienced long-term suppression of your bone marrow. You have had a heart attack within the past 6 months. You have uncontrolled heart rhythm problems. You have already received the maximum allowed doses of certain chemotherapy drugs. You have active and uncontrolled infections. You have received live vaccines within the past month. You have bladder inflammation or blockage of urine flow. You have had another type of cancer within the past 5 years, except for certain types of skin, cervical, or prostate cancer that have been treated and cured. You have uncontrolled severe illness or medical conditions other than the specific type of sarcoma being studied. If you are a female patient, you are pregnant or breastfeeding, or if you are a male or female patient capable of having children, you are not willing to use effective birth control methods. You have any psychological, family, social, or geographical circumstances that could make it difficult for you to follow the study's instructions and schedule. You have known allergies to certain imaging agents and magnetic resonance imaging (MRI).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the experimental arm receive 3 cycles of neoadjuvant chemotherapy followed by surgery. The standard arm undergoes surgery alone.

9-12 weeks

3 visits (in-person) for chemotherapy, 1 visit (in-person) for surgery

Follow-up

Participants are monitored for safety, effectiveness, and recurrence after treatment

8 years

What Are the Treatments Tested in This Trial?

Interventions

• Preoperative chemotherapy
• Surgery

Trial Overview The study is testing if adding preoperative chemotherapy before surgery can improve disease-free survival for patients with high-risk sarcomas. Participants will be randomly assigned to either receive standard surgery alone (control group) or chemotherapy followed by surgery (experimental group).

How Is the Trial Designed?

Group I: Standard arm Experimental Treatment 1 Intervention

Surgery alone

Group II: Experimental arm Experimental Treatment 1 Intervention

Preoperative chemotherapy and surgery

Who Is Running the Clinical Trial?

European Organisation for Research and Treatment of Cancer - EORTC

Lead Sponsor

Trials

417

Recruited

166,000+

Eastern Cooperative Oncology Group

Collaborator

Trials

272

Recruited

153,000+

ECOG-ACRIN Cancer Research Group

Collaborator

Trials

122

Recruited

160,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Japan Clinical Oncology Group

Collaborator

Trials

20

Recruited

4,700+

Australia and New Zealand Sarcoma Association

Collaborator

Trials

1

Recruited

250+

Anticancer Fund, Belgium

Collaborator

Trials

16

Recruited

1,900+

Published Research Related to This Trial

In a study of 81 sarcoma patients who underwent pulmonary metastasectomy after chemotherapy, measurable progression of lung metastases post-chemotherapy was identified as a significant predictor of poor survival outcomes, with a hazard ratio of 4.025.

Patients who experienced progression after chemotherapy had a five-year survival rate of 0%, compared to 32% for those without progression, highlighting the critical impact of post-chemotherapy disease status on prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression after chemotherapy is a novel predictor of poor outcomes after pulmonary metastasectomy in sarcoma patients. Stephens, EH., Blackmon, SH., Correa, AM., et al.[2022]

In a study of 38 patients with soft tissue sarcoma, preoperative therapy, including neoadjuvant radiotherapy and chemotherapy, demonstrated effective local control with only 5.2% experiencing local recurrence after surgery.

The study showed that preoperative treatment was safe and feasible, with most patients undergoing limb-sparing surgeries, and the results suggest that lower limb involvement and marginal excision are associated with worse disease-free survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant treatment of soft tissue sarcoma. Greto, D., Livi, L., Saieva, C., et al.[2021]

The treatment of soft tissue sarcomas has shifted from radical surgeries like amputation to more conservative approaches that combine surgery with radiotherapy, supported by small randomized trials showing better outcomes.

For patients with localized soft tissue sarcomas, adjuvant chemotherapy is standard for certain high-risk subtypes, but its benefits for stage III patients remain unclear, necessitating careful discussion of risks and benefits with these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based recommendations for local therapy for soft tissue sarcomas. Pisters, PW., O'Sullivan, B., Maki, RG.[2022]

The study discusses a new preoperative adjuvant chemotherapy regimen using intra-arterial cisplatin (CDDP) combined with high-dose methotrexate (HDMTX) and adriamycin (ADR) to effectively shrink primary skeletal and soft tissue sarcomas, potentially leading to safer limb-salvage procedures.

This approach aims to not only identify effective postoperative treatments but also to eliminate micrometastatic disease, enhancing overall treatment efficacy for patients with sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preoperative adjuvant chemotherapy of skeletal and soft tissue sarcomas]. Maeyama, I., Furuse, K., Morimoto, K., et al.[2016]

In a study involving eight patients with osteosarcoma and Ewing's sarcoma, early surgery (1 to 4 days after the last chemotherapy dose) was performed without any wound healing or infection complications, suggesting that the timing of surgery after preoperative chemotherapy can be safely adjusted.

The study indicates that combining neoadjuvant chemotherapy with early surgical intervention is feasible and does not delay subsequent chemotherapy treatments, which could improve overall management strategies for high-grade primary bone sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative chemotherapy for primary sarcoma of bone. Chan, KW., Knowling, M., Beauchamp, CP.[2015]

Preoperative chemotherapy has been shown to improve outcomes for certain pediatric sarcomas, leading to interest in applying similar strategies to adult soft tissue sarcomas, especially for tumors larger than 10 cm.

Despite the potential benefits of neoadjuvant chemotherapy in reducing the risk of recurrence and death, there is significant concern about the toxicity of these treatments and a lack of consensus on when they should be used in adult soft tissue sarcoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy: Does Neoadjuvant or Adjuvant Therapy Improve Outcomes? Canter, RJ.[2018]

In a study of 806 patients with localized soft tissue sarcoma, those who received perioperative chemotherapy had a 5-year metastasis-free survival rate of 58%, indicating that this treatment can be effective in real-world settings.

While the long-term outcomes of patients receiving perioperative chemotherapy in routine clinical practice were similar to those in clinical trials, there were notable risks of secondary malignancies and cardiac toxicity, highlighting the importance of considering these potential side effects in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence on perioperative chemotherapy in localized soft tissue sarcoma of the extremities and trunk wall; a population-based study. Boye, K., Lobmaier, I., Kobbeltvedt, MR., et al.[2022]

In a Phase II study involving 70 patients with Stage III non-round cell soft tissue sarcomas in the extremities, pre-operative chemotherapy with doxorubicin and ifosfamide showed promising outcomes, with 5-year overall survival rates of 82.6%.

Despite significant hematological toxicities, including leukopenia and neutropenia, the treatment was feasible and resulted in favorable progression-free survival rates of 75.7% at 2 years and 63.8% at 5 years, indicating potential for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative chemotherapy with ifosfamide and doxorubicin for high-grade soft tissue sarcomas in the extremities (JCOG0304). Tanaka, K., Mizusawa, J., Fukuda, H., et al.[2022]

Preoperative chemotherapy for soft tissue sarcoma can help determine the effectiveness of treatment, potentially allowing for less invasive surgical options and reducing major surgical complications.

The approach to using chemotherapy, surgery, and radiation therapy must be tailored to each patient based on tumor stage and grade, ensuring optimal tumor control while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemotherapy in soft tissue sarcoma. Lokich, JJ.[2013]

Preoperative chemotherapy was found to be effective in evaluating treatment outcomes for patients with osteosarcoma and malignant soft tissue tumors, based on a study of 28 patients.

While changes in radiographic images were similar for malignant bone and soft tissue tumors, the response to chemotherapy was more pronounced in soft tissue tumors, suggesting the need for further research on malignant bone tumors beyond osteosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of preoperative chemotherapy to postoperative chemotherapy in malignant bone and soft tissue tumors]. Furuse, K., Morimoto, K., Yamamoto, K., et al.[2006]

Primary systemic chemotherapy followed by delayed surgery has shown better outcomes for osteogenic sarcomas compared to immediate surgery, allowing for limb preservation and reducing the time lost to postoperative therapy.

At Memorial Sloan Kettering Cancer Center, patients who did not respond favorably to preoperative chemotherapy were switched to alternative regimens, resulting in a 93% disease-free survival rate over a median of 20 months, suggesting that this tailored approach could be beneficial for treating other aggressive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapeutic results in osteosarcoma]. Urban, C., Rosen, G.[2022]

The prognosis for patients with bone and soft tissue sarcomas has improved significantly due to the use of chemotherapy and radical surgery, regardless of whether radiotherapy is included.

Sensitivity to preoperative adjuvant chemotherapy is a key prognostic factor, highlighting its importance in the overall treatment strategy for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prognostic factors of bone and soft tissue sarcomas]. Furuse, K.[2006]

Surgical resection is a crucial treatment for lung metastases from sarcoma, and having multiple bilateral metastases does not prevent surgery from being a viable option.

The effectiveness of preoperative chemotherapy can be assessed through tumor doubling time, which helps predict how well the tumor will respond to treatment and correlates with patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary resection for metastatic sarcoma. Huth, JF., Holmes, EC., Vernon, SE., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5455882/

Neoadjuvant chemotherapy in soft tissue sarcomas Local and distant recurrence occurred in 37% and 26% of patients, respectively, after 5 years, leading to a disease-free and overall survival of 44% and 59%, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e23527

Comparison between preoperative chemoradiation versus ... Neoadjuvant chemotherapy was associated with greater recurrence free survival in patients with high-grade extremity soft tissue sarcomas as compared to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3780573/

Long-Term Results of a Phase 2 Study of Neoadjuvant ... Briefly, only 59% of patients received all 6 cycles of mesna, doxorubicin, ifosfamide, and dacarbazine chemotherapy, and 89% received a preoperative radiation ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08485-1

Efficacy of perioperative chemotherapy for synovial sarcoma The 3-year overall survival, local control, and distant relapse-free survival rates were 79.8%/89.3% (HR = 0.64, p = 0.114), 89.6%/93.0% (HR = ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/jso.70037

Neoadjuvant Chemotherapy for Retroperitoneal Sarcoma ... These findings suggest that neoadjuvant chemotherapy may be associated with worse survival outcomes, although these results remain exploratory ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8534061/

Long-Term Follow-Up of Patients Receiving Neoadjuvant ... The clinical and pathological response to neoadjuvant therapy may influence or possibly predict outcomes. Ten patients (13.5%) in our study showed a pCR, half ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28189277/

Improved Outcomes With the Evolution of a Neoadjuvant ... Thirty-day mortality was 4.5%, and statistically similar between the two groups. The median survival of patients who had R0 resection was 53.5 months compared ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT133881

Neoadjuvant treatment of soft tissue sarcoma The use of preoperative chemotherapy did not result in a gain in clinical outcome.

9. esmoopen.com esmoopen.com/article/S2059-7029(20)32264-X/fulltext

Controversies and consensus of neoadjuvant ... From these results, it is safe to say that it is indeed feasible to give chemotherapy before surgery, which can result in an improvement in survival compared ...