Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High-Grade Neuroendocrine Cancers

Description

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.

Conditions

SCLC, Small Cell Cancer, Advanced Solid Tumor, High Grade Neuroendocrine Cancers

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Study Overview

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Study Details

Study overview

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.

A Phase I/II Trial of Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High Grade Neuroendocrine Cancers

Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High-Grade Neuroendocrine Cancers

Condition
SCLC
Intervention / Treatment

-

Contacts and Locations

Bethesda

National Institutes of Health Clinical Center, Bethesda, Maryland, United States, 20892

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * 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.
  • * Histologically confirmed advanced solid cancers will be eligible.
  • * At least one prior chemotherapy
  • * Individuals with tumor amenable to potentially curative therapy.
  • * Currently receiving any other investigational agents.
  • * Received chemotherapy, or undergone major surgery within the prior 2 weeks and radiotherapy within the last 24 hours.
  • * History of allergic reactions attributed to compounds of similar chemical or biologic composition to (study agent) or other agents used in study.
  • * Symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, individuals who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for 1 week or on physiologic doses of steroids may be enrolled.
  • * Requirement for any medications or substances that are strong inhibitors or inducers of CYP3A during the course of the study are ineligible.
  • * Evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the past 6 months, or psychiatric illness/social situations which would jeopardize compliance with the protocol.
  • * HIV-positive on or off combination antiretroviral therapy are ineligible.
  • * Pregnant individuals are excluded from this study.

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

National Cancer Institute (NCI),

Anish Thomas, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

2027-12-01