Lurbinectedin + Doxorubicin In Leiomyosarcoma

Exclusion Criteria

• •Participants who have received prior anthracycline or trabectedin (Yondelis, ET-743), including prior exposure to doxorubicin or liposomal doxorubicin.
• •Participants who have received more than 2 prior lines of cytotoxic chemotherapy for the phase 1b study and no more than 1 prior line of cytotoxic chemotherapy for the phase 2 study. There is no limit on the number of prior lines of non-cytotoxic chemotherapy (e.g., pazopanib, immunotherapy).
• •Prior exposure to lurbinectedin (PM01183).
• •Participants who have received prior radiation treatment of \> 45 Gy to the pelvis.
• •Participants who have received or undergone prior chemotherapy within 14 days of cycle 1 day 1, therapeutic radiation therapy within 21 days of cycle 1 day 1 or major surgery within 21 days of cycle 1 day 1.
• •Participants who have received prior palliative radiation therapy within 7 days of cycle 1 day 1.
• •Participants who have received prior antibody-based therapy (e.g., nivolumab) within 4 weeks or 3 half-lives (whichever is shorter) of cycle 1 day 1.
• •Participants who have received prior oral small molecule or tyrosine kinase inhibitor (TKI) therapy within 2 weeks or 3 half-lives (whichever is shorter) of cycle 1 day 1.
• •Participants who have not recovered to ≤ Grade 1 or baseline from adverse events attributed to any prior anti-cancer therapy, with the exceptions of alopecia, controlled endocrine toxicity (e.g., hypothyroidism), and cutaneous toxicity which will be permitted at Grade 2.
• •Participants who are receiving any other investigational agents.
• •Participants with known CNS disease involvement, with the exception of patients with brain metastases that have been previously treated and have remained stable on MRI ≥ 28 days prior to cycle 1 day 1 without use of steroids or anti-epileptic medications.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to lurbinectedin or doxorubicin.
• •Participants receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP3A, CYP2D6, or P-gp are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant must be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• •Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic indwelling drains, or psychiatric illness/social situations that would limit compliance with study requirements.
• •History of interstitial pneumonitis or pulmonary fibrosis.
• •Known cardiomyopathy.
• •Pregnant women are excluded from this study because lurbinectedin and doxorubicin are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lurbinectedin or doxorubicin, breastfeeding must be discontinued if the mother is treated with lurbinectedin or doxorubicin. A negative pregnancy test is required for women of childbearing potential prior to the first dose of study medication.
• •Immunocompromised patients, including patients who are known to be seropositive for human immunodeficiency virus (HIV) due to the increased risk of lethal infections when treated with marrow-suppressive therapy. HIV testing is not required as part of screening.