Randomized Phase III Study of Oral Cyclophosphamide vs Doxorubicin in 65 Years or Older Patients With Advanced or Metastatic Soft Tissue Sarcoma: a UNICANCER/GERICO Multicenter Program
Most advanced or metastatic soft tissue sarcoma (STS) are unfortunately incurable, making the preservation of the patient's quality of life a major goal, along with prolonging survival. Age is not a criterion for not providing effective treatment, but the goals of treatment change with age and must be integrated into the treatment decision. Elderly patients prioritise a life free of dependency, preservation of their cognitive functions and quality of life related to their state of health. They are therefore reluctant to receive a treatment that does little to improve life expectancy at the cost of significant functional losses. Patients aged 65 years and older account for one third of all patients with STS. In the absence of dedicated recommendations, these elderly patients are currently receiving doxorubicin-based chemotherapy as first-line treatment (as recommended for younger patients), with a substantial risk of toxicity (especially cardiac). In this specific population, previous studies have shown that oral cyclophosphamide seems to have a promising activity, but also a very acceptable toxicity. Thus, the GERICO study aims to compare standard doxorubicin chemotherapy with oral cyclophosphamide for the treatment of elderly patients with STS.
• Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trust person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent
• Age ≥65 years (inclusions will be managed to ensure that at least 50% of the randomized patients are ≥75 years old)
• Diagnosis of soft-tissue sarcoma histologically confirmed by Réseau de Référence en Pathologie des Sarcomes et des Viscères (RRePS)
• Metastatic or locally advanced disease not amenable to surgery, radiation, or combined modality treatment with curative intent. Palliative radiation therapy is permitted only if direct on nontarget lesion
• Documentation of disease progression within the last 6 months before randomization
• Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT-scan as defined by response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)
• Life expectancy of at least 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• G8 score \>14
⁃ Left ventricular ejection fraction (LVEF) value by echocardiogram or Multiple gated acquisition scanning (MUGA) ≥55%
⁃ Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation:
∙ Absolute neutrophil count (ANC) ≥1,500/mm³
‣ Platelets ≥100,000/mm³
‣ Hemoglobin ≥9.0 g/dL
‣ Serum creatinine ≤2 x upper limit of normal (ULN)
‣ Glomerular filtration rate (GFR) ≥50 ml/min/1.73m² (calculated with MDRD)
‣ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (≤5.0 × ULN for patients with liver involvement of their cancer )
‣ Total bilirubin ≤1.5 X ULN
‣ Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN with liver involvement of their cancer)
‣ serum albumin \>25 g/L
∙ Prothrombin time (PT)/International normalized ratio (INR) ≤1.5 x ULN Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until PT/INR is stable based on a measurement that is pre-dose as defined by the local standard of care
⁃ Male patients must agree to use adequate contraception for the duration of trial participation and up to 6 months after completing treatment/therapy. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care
⁃ Patients must be affiliated to a Social Security System (or equivalent)
⁃ Patient is willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures including follow-up