RECRUITING

NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors

Conditions

Solid Tumor KRAS Mutation-Related Tumors

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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

The goal of this clinical trial is to learn about the safety of NEROFE and doxorubicin and how well it works in patients with advanced/unresectable or metastatic solid KRAS-mutated and ST-positive solid tumors. The main question it aims to answer is to find the recommended dose and scheduled for the combination of NEROFE and doxorubicin. Participants will receive weekly doses of NEROFE and doxorubicin.

Official Title

Phase I Study of NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors

Quick Facts

Study Start:2023-04-12

Study Completion:2026-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05661201

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
* Advanced/unresectable or metastatic solid tumor with a pathogenic KRAS mutation via polymerase chain reaction (PCR), next-generation sequencing (NGS), or other standard test (blood-based DNA testing is allowed) * Presence of tumor ST2 expression via immunochemistry assay * Progression or intolerance to all standard therapies, patient may decline standard therapies and retain eligibility (patients must not have available curative options) * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 * Laboratory	* Age \< 18 years * Prior exposure to anthracycline chemotherapy * Receiving any active anti-cancer therapy while on study treatment * Brain metastases unless they have been previously treated with surgery and/or radiation at least 4 weeks prior to C1D1 and have a baseline MRI that shows no evidence of active/progressing intracranial disease * Anti-tumor therapy within 3 weeks of C1D1 (defined as, but not limited to, cytotoxic chemotherapy, immunotherapy, biological therapy, radiotherapy, and investigational agents), the "wash-out period" * Concurrent severe illness or uncontrolled medical condition that, in the investigator's judgement, would cause unacceptable safety risks * Women who are pregnant or breastfeeding * Concurrent use of an aromatase inhibitor * Psychiatric illness or social situation that would limit compliance with study requirements * Concurrent malignancy or malignancy within 2 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer, or a malignancy that the investigator deems has been definitively treated (e.g. early stage prostate cancer) * Active hepatitis B, C, or HIV (patients with hepatitis C infection are eligible if they have an undetectable viral load following definitive treatment, patients with HIV are eligible if they have an undetectable viral load and a CD4 count above 500 cells/mm3) * Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following: * History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Documented cardiomyopathy * Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening * Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block) * QTcF (using Fridericia's correction) of \> 480 msec * Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: 1. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. 2. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication 3. Inability to determine the QT interval on screening (QTcF, using Fridericia's correction) * Systolic blood pressure (SBP) \>160 mmHg or \<90 mmHg at screening

Inclusion Criteria

Exclusion Criteria

* Advanced/unresectable or metastatic solid tumor with a pathogenic KRAS mutation via polymerase chain reaction (PCR), next-generation sequencing (NGS), or other standard test (blood-based DNA testing is allowed)
* Presence of tumor ST2 expression via immunochemistry assay
* Progression or intolerance to all standard therapies, patient may decline standard therapies and retain eligibility (patients must not have available curative options)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* Laboratory

* Age \< 18 years
* Prior exposure to anthracycline chemotherapy
* Receiving any active anti-cancer therapy while on study treatment
* Brain metastases unless they have been previously treated with surgery and/or radiation at least 4 weeks prior to C1D1 and have a baseline MRI that shows no evidence of active/progressing intracranial disease
* Anti-tumor therapy within 3 weeks of C1D1 (defined as, but not limited to, cytotoxic chemotherapy, immunotherapy, biological therapy, radiotherapy, and investigational agents), the "wash-out period"
* Concurrent severe illness or uncontrolled medical condition that, in the investigator's judgement, would cause unacceptable safety risks
* Women who are pregnant or breastfeeding
* Concurrent use of an aromatase inhibitor
* Psychiatric illness or social situation that would limit compliance with study requirements
* Concurrent malignancy or malignancy within 2 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer, or a malignancy that the investigator deems has been definitively treated (e.g. early stage prostate cancer)
* Active hepatitis B, C, or HIV (patients with hepatitis C infection are eligible if they have an undetectable viral load following definitive treatment, patients with HIV are eligible if they have an undetectable viral load and a CD4 count above 500 cells/mm3)
* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
* History of documented congestive heart failure (New York Heart Association functional classification III-IV)
* Documented cardiomyopathy
* Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)
* QTcF (using Fridericia's correction) of \> 480 msec
* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
1. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
2. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication
3. Inability to determine the QT interval on screening (QTcF, using Fridericia's correction)
* Systolic blood pressure (SBP) \>160 mmHg or \<90 mmHg at screening

Contacts and Locations

Study Contact

Jennifer Montcalm

CONTACT

202-687-8974

jem257@georgetown.edu

Principal Investigator

Benjamin Weinberg, MD

STUDY_CHAIR

Georgetown University

Study Locations (Sites)

Georgetown Lombardi Comprehensive Cancer Center

Washington, District of Columbia, 20007

United States

Collaborators and Investigators

Sponsor: Georgetown University

Benjamin Weinberg, MD, STUDY_CHAIR, Georgetown University

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 Date2023-04-12

Study Completion Date2026-01

Study Record Updates

Study Start Date2023-04-12

Study Completion Date2026-01

Terms related to this study

Additional Relevant MeSH Terms

Solid Tumor
KRAS Mutation-Related Tumors