RECRUITING

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

Conditions

SCLC Small Cell Cancer Advanced Solid Tumor High Grade Neuroendocrine Cancers HGNC M6620

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2021-06-01

Study Completion:2027-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04802174

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.

Inclusion Criteria

Exclusion 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.

Contacts and Locations

Study Contact

Danielle F Pinkiert, R.N.

CONTACT

(240) 858-7566

danielle.pinkiert@nih.gov

Anish Thomas, M.D.

CONTACT

(240) 760-7343

anish.thomas@nih.gov

Principal Investigator

Anish Thomas, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-06-01

Study Completion Date2027-12-01

Study Record Updates

Study Start Date2021-06-01

Study Completion Date2027-12-01

Terms related to this study

Keywords Provided by Researchers

SCLC
HGNC
M6620

Additional Relevant MeSH Terms

SCLC
Small Cell Cancer
Advanced Solid Tumor
High Grade Neuroendocrine Cancers