ACTIVE_NOT_RECRUITING

An Open-Label Intervention Trial to Reduce Senescence and Improve Frailty in Adult Survivors of Childhood Cancer

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FrailtyChildhood Cancer

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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

This is a first-in survivor pilot study with the goal of establishing preliminary evidence of efficacy, safety, and tolerability of two senolytic regimens to reduce markers of cellular senescence (primary outcome: p16\^INK4a) and improve frailty (primary outcome: walking speed) in adult survivors of childhood cancer. If successful, this pilot would provide the preliminary evidence needed for a phase 2, randomized, placebo-controlled trial to establish efficacy. Primary Objective * The primary aim of this proposal is to test the efficacy of two, short duration senolytic regimens: 1) combination of Dasatinib plus Quercetin and 2) Fisetin alone, to improve walking speed and decrease senescent cell abundance in blood (p16\^INKA): * Primary endpoints of this trial will be change in walking speed and senescent cell abundance in blood (p16\^INK4A) determined at baseline and again at 60 days, within an individual arm. Extended follow up at 150 days will assess the permanence of change after completion of the trial. Secondary endpoints of this trial will be effect of intervention on additional measures of frailty (beyond walking speed; Fried criteria) and on other cell senescence markers, markers of inflammation, insulin resistance, bone resorption, and cognitive function. Secondary Objectives The secondary aim is to test the safety and tolerability of two different senolytic therapies. Exploratory Objectives * To compare the efficacy of the two senolytic regimens in improving walking speed and decreasing senescent cell abundance * To evaluate the longitudinal pattern in measures of frailty.

Official Title

SEN-SURVIVORS: An Open-Label Intervention Trial to Reduce Senescence and Improve Frailty in Adult Survivors of Childhood Cancer

Quick Facts

Study Start:2022-06-06
Study Completion:2027-12
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04733534

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:Yes
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Participant in SJLIFE and \> 5 years from diagnosis.
  2. * ≥18 years of age.
  3. * Frail (2 of 4 objectively measured Fried criteria adapted,(excluding self-reported fatigue as a criteria), including abnormal walking speed; muscle strength; activity level; and muscle mass). See Section 5 for details.
  4. * CD3+ T lymphocytes: p16INK4A detected at \<34 cycles by RT PCR.
  5. * Agrees to use contraception as Dasatinib is teratogenic.
  6. * Female participant has a negative pregnancy test.
  7. * QTc \<450 milliseconds in electrocardiogram.
  8. * Able to take oral medications.
  1. * Currently has HIV, Hepatitis B/C, invasive fungal infection
  2. * Anemia or as per clinical judgement.
  3. * Hypersensitivity to study drugs
  4. * New/active malignancy/taking chemotherapy and/or radiation except non-melanoma skin cancers
  5. * Currently taking medications that inhibit or induce CYP3A4 or that are sensitive to substrates or substrates with a narrow therapeutic range for CYP2C8, CYP2C9, or CYP2D6.
  6. * Taking anticoagulants or antimicrobial agents
  7. * Currently taking Quercetin or Fisetin
  8. * Pregnant or nursing at time of enrollment/during the study
  9. * Impaired cognition or motor performance due to congenital defects
  10. * Currently participating in another research intervention to aid walking speed or other measures of frailty including muscle strength; low activity; muscle mass or exhaustion/fatigue
  11. * Participant is a Non-English Speaker
  12. * Uncontrolled pleural/pericardial effusion or ascites
  13. * Subjects on anticoagulant or antiplatelet agents (Warfarin, Clopidogrel \[Plavix\]; Dipyridamole + Aspirin \[Aggrenox\]; Ticagrelor \[Brilintal\]; Prasugrel \[Effient\]; Ticlopidine \[Ticlid\]; or other) who are unable or unwilling to reduce or hold therapy prior to and during the 2-3 day drug dosing. Subjects may continue their previous regimen after drug dosing is complete.
  14. * Cognitive impairment defined by IQ \<80
  15. * Diagnosis of a psychotic disorder
  16. * Laboratory tests as indicated or as per clinical judgement
  17. * Severe hepatic dysfunction with ALT/AST \> 3 times upper limit of normal.
  18. * Total bilirubin \> 2 times upper limit of normal.
  19. * eGFR \<25 ml/min/1.73m2 or as per clinical judgement.
  20. * Hemoglobin \< 7 g/dl; white blood cell count ≤2,000/mm3 (≤2.0 x 109/L) or ≥20,000/mm3 (≥20 x 109/L); platelet count ≤40,000/μL (≤40 x 109/L); absolute neutrophil count ≤1 x 109/L; lymphocyte count \<0.3 x 109/L at screening as a marker of poor nutrition
  21. * Fasting glucose \>300.
  22. * Participant is unable to ambulate

Contacts and Locations

Principal Investigator

Gregory T. Armstrong, MD, MSCE
PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital

Study Locations (Sites)

St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
United States

Collaborators and Investigators

Sponsor: St. Jude Children's Research Hospital

  • Gregory T. Armstrong, MD, MSCE, PRINCIPAL_INVESTIGATOR, St. Jude Children's Research Hospital

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 Date2022-06-06
Study Completion Date2027-12

Study Record Updates

Study Start Date2022-06-06
Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

  • Frailty
  • Childhood Cancer