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Not yet recruitingNCT07716735Updated Aug 6, 2026

Mercaptopurine for the Treatment of Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC), Uterine/Cutaneous Leiomyomas, and Kidney Cancer

A Phase 1 interventional study of Biopsy Procedure and Biospecimen Collection in Advanced Kidney Carcinoma, Advanced Renal Cell Carcinoma and Hereditary Leiomyomatosis and Renal Cell Carcinoma, sponsored by Jonsson Comprehensive Cancer Center. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-06.

Sponsored by Jonsson Comprehensive Cancer Center · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
18
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase I/II trial studies the side effects and best dose of mercaptopurine, and to see how well it works in treating patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC). HLRCC is a rare inherited disorder that increases the risk of developing benign (not cancer) tumors of the skin and the uterus (leiomyomas) and malignant (cancer) tumors of the uterus (leiomyosarcoma) and the kidney. Mercaptopurine is in a class of medications called purine antagonists. It works by stopping the growth of cancer cells.

Read the detailed description

PRIMARY OBJECTIVE:

I. To identify the safety, side effects, and best dose of mercaptopurine (6-MP).

SECONDARY OBJECTIVES:

I. To assess clinical activity in treating metastatic fumarate hydratase (FH) Deficient Kidney Cancer.

II. To assess how treatment impacts uterine fibroid clinical symptoms. III. To determine the change in menstrual bleeding. IV. To evaluate changes in pain due to leiomyomas. V. To evaluate the overall improvement in leiomyoma symptoms.

EXPLORATORY OBJECTIVES:

I. Associate changes in serum thiopurine metabolites (6-methylmercaptopurine [6-MMP] and 6-thioguanine [6-TG]) with efficacy endpoints for kidney cancer, cutaneous leiomyoma, and uterine fibroids.

II. Generate in vitro and in vivo models of cutaneous leiomyomas and kidney cancer that may be useful to predict clinical activity to treatment with 6-MP or purine restriction.

III. Bank clinical specimens (urine, tissue, blood) and tissue for future HLRCC research.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

Patients receive 6-MP orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 26 cycles/2 years (for kidney cohort) or up to 13 cycles/1 year (for skin or uterine cohorts) in the absence of disease progression or unacceptable toxicity. Patients may also undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study (kidney and uterine cohorts only), tumor biopsy on study (kidney cohort only), skin biopsy on study (skin cohort only), and blood sample collection throughout the study (all cohorts).

After completion of study treatment, patients are followed up within 45 days and then every 12 months for 2 years.

02

Conditions studied

  • Advanced Kidney Carcinoma
  • Advanced Renal Cell Carcinoma
  • Hereditary Leiomyomatosis and Renal Cell Carcinoma
  • Metastatic Kidney Carcinoma
  • Metastatic Renal Cell Carcinoma
  • Skin Leiomyoma
  • Stage III Renal Cell Cancer AJCC v8
  • Stage IV Renal Cell Cancer AJCC v8
  • Uterine Corpus Leiomyoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age ≥ 18
  • Disease-causing, germline FH mutation including variants considered either:

    • a) Pathogenic/likely pathogenic OR
    • b) variants of unknown significance (VUS) with immunohistochemical staining showing loss of FH or high 2-SC expression in tumor tissue
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
  • Thiopurine S-methyltransferase (TPMT) and NUDT15 homozygous, wild-type genotype

    • TPMT*1/TPMT*1 and NUDT15*1/ NUDT15*1
  • Calculated creatinine clearance ≥ 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula OR serum creatinine \< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN if liver metastases are present)
  • Total bilirubin \< 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin up to 3.0 mg/dL)
  • Albumin ≥ 2.2 mg/dL
  • White blood cells (WBC) > 2,000/mm\^3
  • Hemoglobin (Hb) ≥ 9
  • Neutrophils > 1,500/mm\^3
  • Platelets > 100,000/mm\^3
  • Inclusion into ≥ 1 of the following symptomatic, disease states listed below:

    • Inclusion allows entry into that cohort for efficacy assessments. Patients can be in ≥ 1 cohort if they have more than one disease manifestation fitting the below criteria. If a patient fits inclusion/exclusion into one cohort and has disease manifestations that are excluded from another cohort, they can still participate in the trial but will not be assessed for efficacy for that specific disease manifestation
  • KIDNEY CANCER COHORT: Advanced, metastatic kidney cancer disease
  • KIDNEY CANCER COHORT: Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • KIDNEY CANCER COHORT: ≥ 1 lines of systemic therapy (not considering adjuvant)
  • UTERINE FIBROIDS COHORT: Age ≥ 18
  • UTERINE FIBROIDS COHORT: Female biologic sex
  • UTERINE FIBROIDS COHORT: Any pre-menopausal patient
  • UTERINE FIBROIDS COHORT: Fibroid-associated symptoms including symptomatic menorrhagia and/or pelvic pain/pressure
  • UTERINE FIBROIDS COHORT: Estimated ≤ 15-week uterus by bimanual exam OR by radiographic parameters (≤ 10 cm max dimension of largest fibroid or estimated weight ≤ 400 g)
  • UTERINE FIBROIDS COHORT: Be willing to use non hormonal contraception if needed
  • CUTANEOUS LEIOMYOMAS COHORT: ≥ 5 cutaneous leiomyomas
  • CUTANEOUS LEIOMYOMAS COHORT: Leiomyoma-associated pain or paresthesia causing weekly pain ≥ 4/10 on a pain scale

Exclusion criteria

Exclusion Criteria:

  • Absolute contraindication to the use of contrast-enhanced imaging for efficacy assessment. If moderate allergy, patients could be allowed if pre-medication can be given to limit adverse reactions. (*Not relevant for skin-only cohort)
  • Presence of untreated brain metastases. Treated brain metastases must be stable for 4 weeks after treatment, have no clinical symptoms, and not be on corticosteroids > 10 mg/day of prednisone-equivalent > 2 weeks prior to treatment. Patients with known leptomeningeal metastases are excluded
  • Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications within 14 days prior to first dose of study drug. An exception is allowed for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry
  • Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results
  • Individuals who are pregnant; negative serum pregnancy tests in patients of childbearing potential and consent to an effective contraceptive method (if needed Centers for Disease Control and Prevention [CDC] guidelines provided) until a minimum of 30 days after cessation of therapy
  • Individuals who wish to continue actively breast-feeding must agree to not breastfeed during the study or for 180 days after the last dose of study treatment
  • An untreated non-renal malignancy with the following exceptions:

    • low risk prostate cancer on active surveillance (National Comprehensive Cancer Network [NCCN] very low/low risk)
    • non-melanoma skin cancer
  • Any prior treated, non-renal malignancy except for those meeting the following characteristics:

    • Treated stage I or II cancer from which the patient is currently in complete remission
    • Stage III cancer in remission for > 2 years and is not receiving any current treatment
    • A hematologic malignancy from which the patient is considered to be in complete remission
  • UTERINE FIBROIDS COHORT: Hormonal management ≤ 2 months of starting treatment. Including gonadotrophin releasing hormone (GnRH) analog, progestins or estrogen (pills or intrauterine devices), or ulipristal acetate
  • UTERINE FIBROIDS COHORT: GnRH analog usage ≤ 12 months of starting treatment
  • UTERINE FIBROIDS COHORT: History of uterine artery embolization
  • UTERINE FIBROIDS COHORT: Prior radiofrequency ablation to a target lesion
  • UTERINE FIBROIDS COHORT: History of MR guided focused ultrasound
  • UTERINE FIBROIDS COHORT: Myomectomy ≤ 1 year of starting therapy
  • UTERINE FIBROIDS COHORT: Concern for gynecologic malignancy
  • UTERINE FIBROIDS COHORT: Any Federation of Gynecology and Obstetrics (FIGO) 1 or FIGO 2 myomas requiring immediate treatment
  • UTERINE FIBROIDS COHORT: Planning pregnancy in the next 6 months
  • UTERINE FIBROIDS COHORT: History of endometrial ablation
  • UTERINE FIBROIDS COHORT: Hormonal intrauterine device (IUD) in place
  • CUTANEOUS LEIOMYOMAS COHORT: Willingness/ability to have all cutaneous lesions completely removed
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
18 participants (estimated)

Study arms

  • Experimental
    Treatment (6-MP)

    Patients receive 6-MP PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 26 cycles/2 years (for kidney cohort) or up to 13 cycles/1 year (for skin or uterine cohorts) in the absence of disease progression or unacceptable toxicity. Patients may also undergo CT or MRI throughout the study (kidney and uterine cohorts only), tumor biopsy on study (kidney cohort only), skin biopsy on study (skin cohort only), and blood sample collection throughout the study (all cohorts).

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Mercaptopurine · Other: Questionnaire Administration · Procedure: Skin Biopsy

Interventions

  • ProcedureBiopsy Procedure

    Undergo tumor biopsy

    Also known as: Biopsy, BIOPSY_TYPE, Bx

  • ProcedureBiospecimen Collection

    Undergo collection of blood

    Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

  • ProcedureComputed Tomography

    Undergo CT

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

  • ProcedureMagnetic Resonance Imaging

    Undergo MRI

    Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

  • DrugMercaptopurine

    Given PO

    Also known as: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine, 6-Mercaptopurine, 6-Mercaptopurine Monohydrate, 6-MP, 6-Purinethiol, 6-Thiopurine, 6-Thioxopurine, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Alti-Mercaptopurine, Azathiopurine, Bw 57-323H, Flocofil, Ismipur, Leukerin, Leupurin, Mercaleukim, Mercaleukin, Mercaptina, Mercaptopurinum, Mercapurin, Mern, NCI-C04886, Puri-Nethol, Purimethol, Purine, 6-mercapto-, Purine-6-thiol (8CI), Purine-6-thiol, monohydrate, Purinethiol, Purinethol, U-4748, WR-2785

  • OtherQuestionnaire Administration

    Ancillary studies

  • ProcedureSkin Biopsy

    Undergo skin biopsy

    Also known as: Biopsy of Skin

05

What researchers measure

Primary outcomes

  1. Maximum tolerated dose (MTD)

    Will be determined using Common Terminology Criteria for Adverse Events version 5.0 grading.

    Time frame: Up to cycle 2 (Cycles = 28 days)

Secondary outcomes

  1. Best overall response (Kidney Cancer Cohort)

    Will be assessed per Response Evaluation Criteria in Solid Tumors. A descriptive summary will report the proportion of patients with complete response, partial response, stable disease, or progressive disease. Patients who are unevaluable will be summarized separately.

    Time frame: Up to 2 years after completion of study treatment

  2. Progression-free survival (PFS) (Kidney Cancer Cohort)

    Kaplan-Meier survival curves will be generated to estimate the distribution of PFS, including median survival and confidence intervals. Landmark analyses will be conducted at 1-year and 2-year time points to estimate the proportion of patients remaining progression-free at these intervals, providing both longitudinal and milestone-based insights into disease control.

    Time frame: From study enrollment to documented disease progression or death from any cause, assessed up to 2 years after completion of study treatment

  3. Tumor volume changes (Uterine Fibroids Cohort)

    Will be assessed via pelvic magnetic resonance imaging. A descriptive summary will report maximal volume reduction from baseline, including the proportion of patients achieving partial or complete response, stable disease, or progression, based on predefined thresholds. Mean and median volume changes will be calculated, and overall response rates will be summarized.

    Time frame: Up to 1 year

  4. Changes in Pictorial Blood Loss Assessment Chart (PBAC) scores (Uterine Fibroids Cohort)

    Will be summarized from baseline to follow-up. Response will be defined as a ≥ 50% reduction in PBAC score. The proportion of responders and non-responders will be reported, along with changes in mean and median scores.

    Time frame: Baseline up to 1 year

  5. Changes in symptom severity (SSS) and health-related quality of life (HRQoL) domains (Uterine Fibroids Cohort)

    Will be assessed using the Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QOL) questionnaire. Response will be defined as a ≥ 10-point improvement in SSS and ≥ 20-point improvement in HRQoL scores. Descriptive statistics will summarize changes from baseline, and response rates will be reported.

    Time frame: Baseline up to 1 year

  6. Changes in leiomyoma pain with/without ice provocation (Cutaneous Leiomyomas Cohort)

    A descriptive summary of the Visual Analogue Scale will be provided from baseline to follow-up scans both with and without ice provocation. The number of responders (improvement in 2 points or 30% reduction) and non-responders will be reported. Similarly, changes in the Brief Pain Inventory-Short Form (BPI-SF) pain severity (average of the 4 questions) will identify the number of responders (2-point reduction or 30% improvement) and non-responders.

    Time frame: Baseline up to 1 year

  7. Changes in leiomyoma-associated interference (Cutaneous Leiomyomas Cohort)

    Will be evaluated using BPI-SF interference scores across all time points. Descriptive statistics will summarize changes from baseline to each follow-up, as well as from baseline to maximal improvement. Response rates will be calculated based on predefined thresholds (≥ 2-point or ≥ 30% improvement), and changes in mean and median scores will be reported.

    Time frame: Baseline up to 1 year

  8. Changes in Patient-Reported Global Change (Cutaneous Leiomyomas Cohort)

    The Patient's Global Impression of Change (PGIC) will be analyzed descriptively to assess perceived improvement in overall skin symptoms. The maximal PGIC score change from baseline will be summarized, and PGIC scores will be visualized across visits using spider plots to illustrate individual and cohort-level trends over time.

    Time frame: Baseline up to 1 year

06

Study locations

1 site
  • UCLA / Jonsson Comprehensive Cancer Center
    Los Angeles, California 90095, United States
07

Registry details

Key details

Study ID
NCT07716735
Lead sponsor
Jonsson Comprehensive Cancer Center
Collaborators
The V Foundation, Phase One Foundation
Responsible party
Sponsor
First posted
Jul 21, 2026
Start date
Dec 1, 2026 (estimated)
Primary completion
Dec 1, 2034 (estimated)
Completion
Dec 1, 2035 (estimated)
Last update
Aug 6, 2026

Study contacts

Brian Shuch
principal investigator · UCLA / Jonsson Comprehensive Cancer Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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