RECRUITING

Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study

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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

To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis

Official Title

Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study

Quick Facts

Study Start:2024-11-26

Study Completion:2028-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05879146

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
1. Age ≥ 18 years. Individuals younger than 18 years old are excluded. More than 99% of the population evaluated at MDACC with a diagnosis of DT is older than 18. Sixty-three percent of the population with a diagnosis of DT evaluated at MDACC are 10 - 54 years old. The remaining 37 percent are older than 54 years old. Additionally, most of the robust data related to dosing or adverse event data currently available on the use of nirogacestat is in adults 2. Histologically documented DT with evidence of radiographic tumor progression (≥ 10% or absolute increase in dimensions of ≥ 10 mm in maximal diameter) in unidimensional measurement within the previous 18 months. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam 1. Recurrent or primary disease 2. Symptomatic disease or impending morbidity (as defined by physician) and patient and physician agree treatment would be of benefit 3. Treatment naïve or progression on or after any prior therapy for DT. Participant must have discontinued prior therapy for at least 28 days or 5 half-lives of the drug, whichever is greater. All toxicities from prior therapy must be resolved to Grade ≤ 1 or clinical baseline. There is no limit on the number of previous systemic treatments received 4. Able to tolerate radiographic progression (up to 20% increase in tumor longest diameter) as determined by treating oncologist based on morbidity and tumor growth is not threatening vital structures 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 6. Are appropriate for systemic therapy 7. Have accessible tumors for serial biopsies 8. Agree to provide new tumor tissue. Tumor tissue from the archival (tumor bank) may be used if the biopsy is performed after discontinuation of prior therapy and the participant must have discontinued prior therapy for at least 28 days or five half-lives of the drug, whichever is greater 9. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated 10. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load 11. Adequate organ and bone marrow function as defined by the following screening laboratory values: 1. Absolute neutrophil count ≥ 1500 cells/μL; 2. Platelets ≥ 100,000 μL; 3. Hemoglobin ≥ 9 g/dL; 4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (isolated bilirubin \> 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%); 5. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase) ≤ 2 × ULN; and 6. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Grade ≤1) 12. Can swallow tablets and have no gastrointestinal conditions affecting absorption 13. Agree to the use of adequate contraception during the treatment period and for at least 4 months for men and women after the last dose of the study treatment (see Appendix 1 for more information) 14. Have the ability to understand and the willingness to sign a written informed consent document 15. English and non-English speaking patients 16. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study 17. Participants with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification; to be eligible for this study, participants should be class 2B or better 18. Ability to understand and the willingness to sign a written informed consent document	1. Unable to undergo serial biopsies 2. Participants with familial adenomatous polyposis 3. Unable to tolerate MRI or for whom MRI is contraindicated 4. Pregnant or breastfeeding women are excluded from this study. Based on findings in animal studies, oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than adult human exposures at the recommended dose of 150 mg twice daily. Nirogacestat should be avoided during pregnancy 5. Known hypersensitivity to nirogacestat or any of its excipients 6. Participants requiring the use of any excluded concomitant medications listed in Table 2 during the course of the study 7. Unable to comply with study-related procedures in the opinion of the investigator 8. Patients with cognitive impairment requiring a legally authorized representative for consent 9. Patients with uncontrolled intercurrent illness (Indicate clearly what type or extent) 10. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with positive viral load will be excluded 11. Patients with psychiatric illness/social situations that would limit compliance with study requirements 12. Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia 13. Patients who are receiving any other investigational agents 14. Patients with an additional malignancy and brain metastases. There is not enough evidence of the effects of nirogacestat in other malignancies at this time 15. Participant has experienced any of the following within 6 months of signing informed consent: 15.1 clinically significant cardiac disease (New York Heart Association Class III or IV); 15.2 myocardial infarction; 15.3 severe/unstable angina; 15.4 coronary/peripheral artery bypass graft; 15.5 symptomatic congestive heart failure; 15.6 cerebrovascular accident; 15.7 transient ischemic attack; or 15.8 symptomatic pulmonary embolism.

Inclusion Criteria

Exclusion Criteria

1. Age ≥ 18 years. Individuals younger than 18 years old are excluded. More than 99% of the population evaluated at MDACC with a diagnosis of DT is older than 18. Sixty-three percent of the population with a diagnosis of DT evaluated at MDACC are 10 - 54 years old. The remaining 37 percent are older than 54 years old. Additionally, most of the robust data related to dosing or adverse event data currently available on the use of nirogacestat is in adults
2. Histologically documented DT with evidence of radiographic tumor progression (≥ 10% or absolute increase in dimensions of ≥ 10 mm in maximal diameter) in unidimensional measurement within the previous 18 months. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
1. Recurrent or primary disease
2. Symptomatic disease or impending morbidity (as defined by physician) and patient and physician agree treatment would be of benefit
3. Treatment naïve or progression on or after any prior therapy for DT. Participant must have discontinued prior therapy for at least 28 days or 5 half-lives of the drug, whichever is greater. All toxicities from prior therapy must be resolved to Grade ≤ 1 or clinical baseline. There is no limit on the number of previous systemic treatments received
4. Able to tolerate radiographic progression (up to 20% increase in tumor longest diameter) as determined by treating oncologist based on morbidity and tumor growth is not threatening vital structures
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Are appropriate for systemic therapy
7. Have accessible tumors for serial biopsies
8. Agree to provide new tumor tissue. Tumor tissue from the archival (tumor bank) may be used if the biopsy is performed after discontinuation of prior therapy and the participant must have discontinued prior therapy for at least 28 days or five half-lives of the drug, whichever is greater
9. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
10. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
11. Adequate organ and bone marrow function as defined by the following screening laboratory values:
1. Absolute neutrophil count ≥ 1500 cells/μL;
2. Platelets ≥ 100,000 μL;
3. Hemoglobin ≥ 9 g/dL;
4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (isolated bilirubin \> 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%);
5. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase) ≤ 2 × ULN; and
6. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Grade ≤1)
12. Can swallow tablets and have no gastrointestinal conditions affecting absorption
13. Agree to the use of adequate contraception during the treatment period and for at least 4 months for men and women after the last dose of the study treatment (see Appendix 1 for more information)
14. Have the ability to understand and the willingness to sign a written informed consent document
15. English and non-English speaking patients
16. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study
17. Participants with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification; to be eligible for this study, participants should be class 2B or better
18. Ability to understand and the willingness to sign a written informed consent document

1. Unable to undergo serial biopsies
2. Participants with familial adenomatous polyposis
3. Unable to tolerate MRI or for whom MRI is contraindicated
4. Pregnant or breastfeeding women are excluded from this study. Based on findings in animal studies, oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than adult human exposures at the recommended dose of 150 mg twice daily. Nirogacestat should be avoided during pregnancy
5. Known hypersensitivity to nirogacestat or any of its excipients
6. Participants requiring the use of any excluded concomitant medications listed in Table 2 during the course of the study
7. Unable to comply with study-related procedures in the opinion of the investigator
8. Patients with cognitive impairment requiring a legally authorized representative for consent
9. Patients with uncontrolled intercurrent illness (Indicate clearly what type or extent)
10. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with positive viral load will be excluded
11. Patients with psychiatric illness/social situations that would limit compliance with study requirements
12. Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia
13. Patients who are receiving any other investigational agents
14. Patients with an additional malignancy and brain metastases. There is not enough evidence of the effects of nirogacestat in other malignancies at this time
15. Participant has experienced any of the following within 6 months of signing informed consent:
15.1 clinically significant cardiac disease (New York Heart Association Class III or IV); 15.2 myocardial infarction; 15.3 severe/unstable angina; 15.4 coronary/peripheral artery bypass graft; 15.5 symptomatic congestive heart failure; 15.6 cerebrovascular accident; 15.7 transient ischemic attack; or 15.8 symptomatic pulmonary embolism.

Contacts and Locations

Study Contact

Keila Torres, MD,PHD

CONTACT

(713) 792-4242

ketorres@mdanderson.org

Principal Investigator

Keila Torres, MD,PHD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Keila Torres, MD,PHD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

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 Date2024-11-26

Study Completion Date2028-01-31

Study Record Updates

Study Start Date2024-11-26

Study Completion Date2028-01-31

Terms related to this study

Additional Relevant MeSH Terms

Tumor