Preoperative Chemotherapy + Surgery for Sarcoma
(STRASS2 Trial)
Recruiting in Palo Alto (17 mi)
+148 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a multicenter, randomized, open label phase lll trial to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease free survival.
After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.
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.
What data supports the idea that Preoperative Chemotherapy + Surgery for Sarcoma is an effective treatment?
The available research shows that using preoperative chemotherapy before surgery for sarcoma can lead to better outcomes. For example, in osteosarcoma, this approach has resulted in a 93% disease-free survival rate over a median of 20 months. This means that most patients did not show signs of the disease during this period. Additionally, preoperative chemotherapy can make surgery less invasive, allowing for limb-sparing procedures instead of more drastic surgeries. This treatment strategy also helps identify patients who might need different therapies if the initial chemotherapy isn't effective, improving overall treatment results.
12345What safety data exists for preoperative chemotherapy and surgery for sarcoma?
The safety data for preoperative chemotherapy and surgery for sarcoma is limited and varies. Real-world data suggests that perioperative chemotherapy is used in high-risk, localized soft tissue sarcoma, but potential toxicity from cytotoxic chemotherapy is substantial. There is little consensus on the indications for chemotherapy in the adjuvant/neoadjuvant setting. Some studies have evaluated toxicity and survival outcomes, but the efficacy and safety remain controversial, with few prospective studies available. Adjuvant chemotherapy is standard for certain sarcoma subtypes, but not for low- and intermediate-risk disease, and the benefits for high-risk disease are not convincingly demonstrated.
678910Eligibility Criteria
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.
Criteria for non-resectability are: Involvement of the superior mesenteric artery, aorta, coeliac trunk and/or portal vein. Involvement of bone. Growth into the spinal canal. Progression of retro-hepatic inferior vena cava leiomyosarcoma towards the right atrium. Infiltration of multiple major organs like liver, pancreas and/or major vessels. Tumor not previously treated (no previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy). Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging within the 28 days prior to randomization. CT thorax abdomen pelvis with IV contrast is the preferred imaging modality. In case of any contra-indications (medical or regulatory), it is allowed to perform a non-contrast CT thorax + MRI abdomen & pelvis. ≥ 18 years old (no upper age limit). WHO (World Health Organization) performance status ≤ 2. Adequate haematological and organ function: Haematological: haemoglobin > 9.0 g/dL or 5.6 mmol/L, absolute neutrophils > 1.5 x 109/L, platelets > 100 x 109/L Note: Platelet transfusions is allowed to achieve these baseline values. Renal: estimated glomerular filtration rate (eGFR) > 50 ml/min/m2; No proteinuria CTCAE ≥ grade 2. Hepatic: Bilirubin ≤ 1.0 times upper limit of normal (1.0xULN) of institutional limits, ALT (alanine aminotransferase) and/or AST (aspartate transaminase) ≤1.5 x ULN. If isolated elevated bilirubin <2 x ULN and Gilberts syndrome suspected, suggest repeating bloods after food. If bilirubin improves to meet the criteria above this is acceptable. More severe persistent hepatic impairment of whatever cause would exclude the patient from treatment till resolved. Heart: Clinically normal cardiac function based on left ventricular ejection fraction (LVEF ≥ 50%) as assessed either by multi-gated acquisition scan (MUGA) or cardiac ultrasound and 12 lead ECG without clinically relevant abnormalities. American Society of Anesthesiologist (ASA) score < 3. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment or surgery. Note: a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Patients of childbearing / reproductive potential should use highly effective birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last dose of treatment or date of surgery. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include: Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal). Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable). Intrauterine device (IUD). Intrauterine hormone-releasing system (IUS). Bilateral tubal occlusion. Vasectomized partner. Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient). Female subjects who are breast feeding should discontinue nursing prior to the first day of study treatment and until 6 months after the last study treatment. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
+2 more
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).
Trial Timeline
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
Participant Groups
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).
2Treatment groups
Experimental Treatment
Group I: Standard armExperimental Treatment1 Intervention
Surgery alone
Group II: Experimental armExperimental Treatment1 Intervention
Preoperative chemotherapy and surgery
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutchinson Cancer CenterSeattle, WA
Stony Brook University Medical CenterStony Brook, NY
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
University of Illinois at Chicago MBCCOPChicago, IL
More Trial Locations
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Who Is Running the Clinical Trial?
European Organisation for Research and Treatment of Cancer - EORTCLead Sponsor
Eastern Cooperative Oncology GroupCollaborator
ECOG-ACRIN Cancer Research GroupCollaborator
Canadian Cancer Trials GroupCollaborator
Japan Clinical Oncology GroupCollaborator
Australia and New Zealand Sarcoma AssociationCollaborator
Anticancer Fund, BelgiumCollaborator
References
[New therapeutic results in osteosarcoma]. [2022]Primary systemic chemotherapy and delayed surgery, if it is surgically feasible with preservation of the limb, has produced better results in osteogenic sarcomas than primary surgery with loss of time due to the postoperative therapy free interval. Histologic examination of the resected tumor determines the effect of preoperative chemotherapy and identifies patients at high risk. These patients not having a favorable effect on preoperative chemotherapy can be placed on an alternative postoperative regimen before relapsing clinically. These earlier changes of chemotherapeutic strategy in patients with histologically proven ineffective chemotherapy has yielded further improvement in treatment results in patients with osteogenic sarcomas with a 93% disease free survival (median 20 months) to date using an individualized taylored treatment approach at the Memorial Sloan Kettering Cancer Center/New York. Now that effective chemotherapy is available for many other malignant tumors this model of "neo-adjuvant" chemotherapy could also serve as a model for the treatment of other highly malignant tumours.
Preoperative chemotherapy in soft tissue sarcoma. [2013]The preoperative use of chemotherapy in the management of soft tissue sarcoma is a recent concept in the multidisciplinary management of neoplasia related to the development of more effective drug combinations. The reason for chemotherapy preoperatively is to define the effectiveness of drug treatment, permitting a rational basis for long term adjuvant treatment. In addition, major surgical morbidity may be precluded if chemotherapy is effective, allowing lesser surgical procedures, such as limb-sparing local resection. Patient selection for this approach must be individualized and is based upon the major determinants of prognosis, including the stage of the tumor according to the TNM and G--grade--classification. Radiation therapy is an essential component of the multimodality approach to soft tissue sarcomas, and the interaction of all three therapeutic modalities must provide optimal tumor control and minimal morbidity.
Progression after chemotherapy is a novel predictor of poor outcomes after pulmonary metastasectomy in sarcoma patients. [2022]Sarcoma patients with pulmonary metastases frequently receive chemotherapy before resection. We hypothesized that measurable progression after chemotherapy is a novel predictor of poor outcomes in sarcoma patients undergoing pulmonary metastasectomy.
[Prognostic factors of bone and soft tissue sarcomas]. [2006]Prognostic factors of bone and soft tissue sarcomas were analyzed and common factors observed were the size of tumor, histological malignancy and metastasis. When these factors were viewed in advance of treatment, however, the prognosis of the sarcomas has definitely improved with chemotherapy and radical surgery of primary and metastatic lesions, combined and not combined with radiotherapy. Preoperative adjuvant chemotherapy now plays an important role in the whole strategic regimen of cancer treatment. Of various prognostic factors, the dominance of the sensitivity of each patient to preoperative adjuvant chemotherapy was indicated.
Pulmonary resection for metastatic sarcoma. [2019]Surgical resection plays an important role in the treatment of sarcoma that is metastatic to the lung. Multiple bilateral metastases are not contraindications to surgery. The rapidity of growth and the response to chemotherapy can be accurately determined by the tumor doubling time. Preoperative chemotherapy provides an in vivo measurement of tumor sensitivity, and the response to chemotherapy correlates with prognosis. Since residual microscopic pulmonary disease appears to be responsible for most failures after thoracotomy, attention should be directed toward delivering more effective adjuvant therapy to the lungs.
Real-world evidence on perioperative chemotherapy in localized soft tissue sarcoma of the extremities and trunk wall; a population-based study. [2022]Data from the real-world setting on perioperative chemotherapy in high-risk, localized soft tissue sarcoma (STS) is limited. Real-world data (RWD) includes data derived from patients treated outside clinical trials and often captures long-term follow-up not recorded in clinical trials. The aim of this study was to provide population-based, real-world evidence on perioperative chemotherapy in localized STS.
Chemotherapy: Does Neoadjuvant or Adjuvant Therapy Improve Outcomes? [2018]Since preoperative chemotherapy has been clearly shown to improve outcomes for patients with Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma, practitioners have attempted to extend the use of adjuvant/neoadjuvant chemotherapy to other types of adult soft tissue sarcoma. Given the high risk of distant recurrence and disease-specific death for patients with soft tissue sarcoma tumors larger than 10 cm, these patients should be considered candidates for neoadjuvant chemotherapy as well as investigational therapies. Yet, potential toxicity from cytotoxic chemotherapy is substantial, and there remains little consensus and wide variation regarding the indications for use of chemotherapy in the adjuvant/neoadjuvant setting.
Neoadjuvant treatment of soft tissue sarcoma. [2021]The aim of this study was to evaluate disease-free survival (DFS), overall survival and toxicity of patients who underwent preoperative therapy for soft tissue sarcoma.
Perioperative chemotherapy with ifosfamide and doxorubicin for high-grade soft tissue sarcomas in the extremities (JCOG0304). [2022]The efficacy of perioperative chemotherapy for soft tissue sarcomas is controversial and only a few prospective studies of pre-operative chemotherapy for soft tissue sarcomas in the extremities have been reported. We therefore carried out Phase II study of perioperative chemotherapy for patients with soft tissue sarcomas in the extremities.
Evidence-based recommendations for local therapy for soft tissue sarcomas. [2022]There has been a gradual migration in the local treatment of soft tissue sarcomas from amputation and similar radical resectional approaches to more conservative, function-preserving surgery combined with radiotherapy. This progress has been made possible by small, single-institution, randomized trials that demonstrated the superiority of this more conservative, combined-modality approach. In the new millennium, attention has shifted to defining subsets of patients who might be adequately treated by surgery alone and defining the optimal sequence of surgery and radiation for patients who require both types of local therapy. There remains considerable discussion and debate surrounding the issue of pre- and postoperative chemotherapy for patients with localized soft tissue sarcomas. Adjuvant chemotherapy is a standard of care for adults who have the subtypes of soft tissue sarcomas that typically occur in pediatric patients (Ewing sarcoma, rhabdomyosarcoma), and just as clearly, adjuvant chemotherapy is not warranted in patients with low- and intermediate-risk disease (stages I and II). For patients with higher risk disease (stage III), the available randomized trials do not convincingly demonstrate a clinical benefit to adjuvant chemotherapy. As such, a complete accounting of potential risks and benefits is appropriate when discussing adjuvant chemotherapy with patients who have stage III disease.
[Preoperative adjuvant chemotherapy of skeletal and soft tissue sarcomas]. [2016]Preoperative adjuvant chemotherapy for skeletal and soft tissue sarcomas requires: (1) correct identification of the effective postoperative adjuvant chemotherapy, (2) eradication of any of the micrometastatic foci that may have already occurred in many of the patients with these sarcomas, (3) easier and safer limb-salvage procedure, being clearly defined, with shrinkage of the primary lesion. For this purpose, a preoperative adjuvant chemotherapy regimen making practical use of intra-arterial CDDP (cis-dichlorodiammineplatinum II) infusion is desired in multi-drug combined chemotherapeutic treatment, including HDMTX (high-dose methotrexate), ADR (adriamycin) and CDDP. In this paper, the clinical application of preoperative adjuvant chemotherapy to skeletal and soft tissue sarcomas with combination of HDMTX and CDDP is presented in the light of the observations of tumor response to these anticancer agents, and the possibility of to establishing a new preoperative adjuvant protocol is discussed.
Perioperative chemotherapy for primary sarcoma of bone. [2015]Preoperative chemotherapy for primary osteosarcoma has usually been accompanied by a prolonged delay between withdrawal before operation and resumption after. This is because animal studies showed impaired wound healing associated with perioperative chemotherapy. Clinical studies, however, have not shown this to be the case. The authors describe their experience in eight patients who had osteosarcoma and Ewing's sarcoma of the extremities and received one to three cycles of chemotherapy preoperatively. Chemotherapy consisted of Adriamycin, cis-platinum and vincristine. Definitive surgery on the primary tumour was done 1 to 4 days after the last dose. Amputation was performed on seven patients and tumour resection for limb salvage on one. No wound healing or infectious complications were encountered. The ensuing course of chemotherapy was not delayed by the surgical procedure. The authors conclude that it is feasible to combine neoadjuvant chemotherapy and early surgery in the management of high-grade primary bone sarcoma.
[Application of preoperative chemotherapy to postoperative chemotherapy in malignant bone and soft tissue tumors]. [2006]We analyzed the effectiveness of preoperative chemotherapy mainly with radiographic images in 9 patients with osteosarcoma, 5 patients with other malignant bone tumor and 14 patients with malignant soft tissue tumor. Judging from the application of preoperative to postoperative chemotherapy and outcome, its evaluation was useful in osteosarcoma and malignant soft tissue tumors. Changes in radiographic images by preoperative chemotherapy were the same in malignant bone and soft tissue tumors, but the reactivity of the latter was more evident. In malignant bone and soft tissue tumors, the effects of preoperative chemotherapy should be evaluated for the cases with resection of primary tumor. Malignant bone tumors excepting osteosarcoma also should be assessed through further accumulation of many more cases.