Sequential Neoadjuvant Ifosfamide and Doxorubicin in Localized High-grade Soft Tissue Sarcoma of Extremities and Trunk Wall
Nearly half of patients with high-grade, localized soft tissue sarcoma (STS) of extremities and trunk wall develop disease recurrence after local therapy. Adjuvant chemotherapy with ifosfamide and doxorubicin may improve long-term disease-free survival, but the benefit of adjuvant treatment is limited and predictive factors for treatment response are lacking. The aim of this study is to explore sequential treatment with ifosfamide and doxorubicin in a neoadjuvant setting and to investigate biomarkers predictive of treatment response.
• ≥ 18 years of age at the time of informed consent.
• Histological diagnosis of soft tissue sarcoma belonging to one of the following histotypes:
∙ Leiomyosarcoma
‣ Malignant peripheral nerve sheath tumor
‣ Undifferentiated pleomorphic sarcoma
‣ Myxofibrosarcoma
‣ Synovial sarcoma
‣ Pleomorphic liposarcoma
‣ Pleomorphic rhabdomyosarcoma
‣ Unclassified spindle cell sarcoma
• Malignancy grade ≥ 2 according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system.
• Tumor localized in extremity, girdle and/or trunk wall.
• Primary tumor size ≥5.0 cm as measured in the longest diameter on diagnostic MRI or CT scan.
• Primary tumor location below the superficial fascia or involving the superficial fascia, i.e. deep-seated according to the World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone (4th edition, 2013).
• The primary tumor must be available for biopsy collection at protocol inclusion.
• Patients must have a measurable tumor according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
⁃ Before patient registration, written informed consent must be given according to national and local regulations.
⁃ Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments:
• Hemoglobin ≥ 8.0 g/dL
∙ Neutrophil count ≥ 1.0 x 109/L
∙ Platelet count ≥ 75 x 109/L
∙ Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
∙ Creatinine clearance ≥ 60 ml/min based on Cockcroft Gault estimation or direct measurement
⁃ Negative Hepatitis B and C and HIV serology.
⁃ Adequate contraception in women of childbearing potential (WOCBP) and their fertile partners during the study and until 6 months after end of study treatment. WOCBP should have a negative highly sensitive serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. A woman is considered fertile following menarche and until becoming post-menopausal unless permanently sterile. WOCBP should be willing to use one of the mentioned highly effective methods of birth control mentioned below or be surgically sterile, or abstain from heterosexual activity for the course of the study through 1 year after the last dose of study medication. Methods considered as highly effective birth control methods include combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal, injectable, implantable or transdermal), intrauterine device (including hormone-releasing), male condom, bilateral tubal occlusion, vasectomised partner or sexual abstinence (see appendix 5 for definitions).