A Phase II Study on Efficacy and Tolerability of Weekly Doxorubicin in Elderly Patients With Advanced or Metastatic Leiomyosarcoma of Soft Tissue
The overall goal of this Phase 2 study is to determine the efficacy of a lower dose weekly schedule of doxorubicin in patients with unresectable leiomyosarcomas aged 65-100 years old. While doxorubicin is the standard of care therapy for sarcomas not removable by surgery, older or more frail patients may struggle to tolerate side effects of the treatment including immune cell suppression. Previous studies have suggested that similar anti-tumor activity can be obtained using a lower dose, weekly administration schedule of doxorubicin. In this study, the investigators will determine progression-free survival rate at 12 weeks, with secondary endpoints including quality of life and adverse events in this population. Importantly, doxorubicin can also induce immune stimulatory effects when administered at lower doses, based on animal data. Thus, correlative samples including blood and tumor biopsies will also explore the effects of immune cells and foreignness of the tumor prior to and during treatment in study patients.
• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Be male or female aged 65-100 years at the time of signing informed consent.
• Have a histological diagnosis of advanced or metastatic soft tissue leiomyosarcoma (LMS) (by local pathology review), not curable by surgery, for which treatment with weekly doxorubicin is deemed appropriate by the investigator.
• Have measurable or non-measurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors. Tumors within a previously irradiated field will be designated as nontarget lesions unless progression is documented, or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy.
• Have received 0 to 4 prior systemic therapies for metastatic sarcoma and NO prior anthracyclines. Re-treatment with the same drug or regimen after interruption (i.e. chemotherapy holiday) is not considered a new line of treatment, and those patients are eligible.
• Adequate organ function
• ECOG performance status of 0, 1 or 2.
• Patients must consent and be willing to undergo tumor core needle biopsies at two time points: 1. Baseline, 2. Cycle 2 Day 1 (+/- 7 days); a third biopsy for off-study/progression is optional but advised. At least one tumor site must be amenable to biopsy in the judgment of the interventional radiologist.
⁃ Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Prior history of vasectomy does NOT replace requirement for contraceptive use.
⁃ Female subjects will be post-menopausal.
⁃ Subjects must either possess or undergo placement of central venous catheter, including pheresis or trifusion catheter, PICC line, or port.