A Phase I/II Trial of Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High Grade Neuroendocrine Cancers
Background: Small cell lung cancer (SCLC) and high-grade neuroendocrine cancers (HGNEC) are aggressive neuroendocrine cancers. At first, SCLC and HGNEC respond to chemotherapy. But then they relapse quickly and become resistant to treatment. Researchers want to see if a combination of drugs can help.
Objective: To see if the combination of lurbinectedin and berzosertib may be effective to shrink SCLC and HGNEC tumors, and to find the best dose of the combination.
Eligibility: Adults ages 18 and older with a solid tumor, SCLC, or HGNEC.
Design: Participants will get lurbinectedin by intravenous (IV) catheter on Day 1 of each cycle (1 cycle = 21 days). They will get berzosertib by IV on Days 1 and 2 of each cycle. Participants will continue to receive treatment as long as they are benefiting from treatment. Participants will have physical exams and blood tests. Their symptoms, medicines, and ability to perform their normal activities will be reviewed. Participants will have electrocardiograms to test heart function. Sticky pads will be placed on their chest, arms, and legs. Participants will give blood and hair samples for research. They may have optional tumor biopsies. Participants will have computed tomography (CT) scans to see if the treatment is effective. Participants will have a follow-up visit 1 month after treatment ends. Then they will be followed by email or phone for the rest of their life.
• Both Phase I and Phase II:
• \>= 18 years of age.
• ECOG performance status \<= 2
• Measurable disease, per RECIST 1.1. Individuals with evaluable, but not measurable disease will be eligible for Phase I.
• Adequate organ functions
‣ Hemoglobin \>= 9.0 g/dL
⁃ Absolute neutrophil count \>= 1.5x10\^9/L
⁃ Platelets \>= 100x10\^9/L
⁃ Total Bilirubin \<= 2.0 mg/dL
⁃ Transaminases \<= 2 x ULN or if liver metastases were present, \<= 3 x ULN
⁃ Creatinine \<= 1.5 mg/dL or creatinine clearance by Cockcroft-Gault formula \>= 60 mL/min
• Ability to understand and the willingness to sign a written informed consent document.
• Individuals of child-bearing potential (IOCBP) and individuals able to father a child must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during study participation and for 6 months after the last dose of berzosertib/lurbinectedin for IOCBP and for 4 months after lurbinectedin or 3 months after berzosertib for individuals able to father children.
∙ Phase I:
• Histologically confirmed advanced solid cancers will be eligible.
• At least one prior chemotherapy
∙ Phase II:
∙ \- Histological confirmation of SCLC or HGNEC. Although NCI confirmation of pathology is not required prior to starting treatment, every effort will be made to obtain outside pathology to be reviewed by an NCI pathologist.