JCOG2214INT: A randomized phase III study of neoadjuvant chemotherapy followed by surgery versus surgery alone for patients with High Risk RetroPeritoneal Sarcoma

JRCT ID: jRCTs031230482

Registered date:28/11/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Primary high risk leiomyosarcoma or dedifferentiated liposarcoma of the retroperitoneum.
• Date of first enrollment: 28/11/2023
• Target sample size: 250
• Countries of recruitment: Australia,Japan,Canada,Japan,Cyprus,Japan,Czechia,Japan,Denmark,Japan,France,Japan,Germany,Japan,Italy,Japan,Netherlands,Japan,Poland,Japan,Slovakia,Japan,Spain,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Patients in the standard arm (surgery alone) will undergo large en- bloc curative intent surgery will be performed within 4 weeks following randomization.

Patients in the experimental arm will receive 3 cycles of neoadjuvant chemotherapy starting within 2 weeks from randomization.
Dedifferentiated liposarcoma: Doxorubicin 75 mg/m2 + Ifosfamide 9 g/m2 Q3 weeks.
Leiomyosarcoma: Doxorubicin 75 mg/m2 + Dacarbazine 1g/m2 Q3 weeks.

Outcome(s)

• Primary Outcome: Disease free survival

Secondary Outcome

* Overall survival
* Recurrence free survival
* Distant metastases free survival
* Cumulative incidence of local recurrences
* Cumulative incidence of distant metastases
* Radiological response to neoadjuvant chemotherapy according to RECIST
* Radiological response to neoadjuvant chemotherapy according to CHOI
* Pathological response
* Safety and toxicity of neoadjuvant chemotherapy
* Perioperative complications
* Late complications
* Health-Related Quality of life (EORTC QLQ-C30 + Item list from QLQ-STO22)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

* Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis (LPS: Grade 3 DDLPS OR confirmed Grade 2 DDLPS on biopsy only if FNCLCC score = 5 AND clear necrosis on imaging. LMS: Any grade and size > 5 cm)
* Unifocal tumour
* Resectable tumour
* Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging within the 28 days prior to randomization.
* Collection of tumor tissue and blood samples for central pathology review and translational research are mandatory.
* >= 18 years old (no upper age limit)
* WHO performance status <= 2
* Adequate haematological and organ function assessed within 21 days prior to randomization
* American Society of Anaesthesiologist (ASA) score < 3
* Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization.
* For men in the experimental arm: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm.
* Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclude criteria

* Sarcoma originating from bone structure, abdominal or gynecological viscera
* Extension through the sciatic notch or across the diaphragm
* Metastatic disease
* Any previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy for the present tumour
* Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients
* Congestive heart failure
* Angina pectoris
* Myocardial infarction within 1 year before randomization
* Uncontrolled arterial hypertension defined as blood pressure >= 150/100 mm Hg despite optimal medical therapy
* Uncontrolled cardiac arrhythmia
* Previous treatment with maximum cumulative doses (450mg/m2 Doxorubicin or equivalent 900mg/m2 Epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones
* Active and uncontrolled infections
* Vaccination with live vaccines within 30 days prior to study entry
* Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow.
* Other invasive malignancy within 5 years, with the exception of adequately treated non-melanoma skin cancer, localized cervical cancer, localized and Gleason <= 6prostate cancer.
* Uncontrolled severe illness, infection, medical condition (including uncontrolled diabetes), other than the primary LPS or LMS of the retroperitoneum.
* Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control method.
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial
* Known contraindication to imaging tracer and to MRI

Related Information

• Primary Sponsor: OZAKI Toshifumi
• Source(s) of Monetary Support: National Cancer Center Japan
• Secondary ID(s): NCT04031677