Doxorubicin for the Treatment of Elderly Patients with Advanced or Metastatic Soft Tissue Leiomyosarcoma

Inclusion Criteria

• 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 (RECIST 1.1). 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
• Absolute neutrophil count (ANC) ≥ 1,000/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 8 g/dL without erythropoietin (EPO) dependency
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN * Exception: Subjects with known history of Gilbert’s disease should be ≤ 1.5 X of the patient’s prior baseline
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin > 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Patients must consent and be willing to undergo tumor core needle biopsies at two timepoints: 1. baseline, 2. cycle 2 day 1 (+/- 7 days); a third biopsy for off- treatment or 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, peripherally inserted central catheter (PICC) line, or port

Exclusion Criteria

• Prior therapy with anthracycline
• Hypersensitivity to doxorubicin or any excipients
• Patients may not be receiving any other investigational agents (within 28 days prior to cycle 1, day 1)
• Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 21 days prior to cycle 1, day 1 or has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 21 days earlier. Subjects with ≤ grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study. Note: If a subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
• Patients with underlying immune deficiency, chronic infections including hepatitis, and known history of HIV or tuberculosis (TB)
• Patients with underlying hematologic issues including bleeding diathesis, such as known previous gastrointestinal (GI) bleeding requiring intervention within the past 6 months. Newly diagnosed pulmonary emboli or deep venous thrombosis must be clinically stable on anticoagulation regimen for ≥ 2 weeks as of cycle 1 day 1
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Subjects with previously treated brain metastases may participate provided they are stable based on the following: 1) MRI brain obtained during screening evaluations shows no radiographic evidence of progression or new lesions, 2) any neurologic symptoms have returned to baseline. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients without a known history of brain metastases do not require screening brain MRI prior to study enrollment
• Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
• Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Prolonged corrected QT (QTc) interval on screening electrocardiogram (EKG) > 475 ms
• Left ventricular ejection fraction < 50% by 2 dimensional (2D) ECHO or MUGA scan at screening
• Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the investigator(s) to interfere or limit compliance with study requirements/treatment, including New York Heart Association (NYHA) class II or greater heart disease