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

NCT07716735 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 25-2484NCI-2026-04727
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

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

  Up to cycle 2 (Cycles = 28 days)

Secondary Outcomes (8)

• Best overall response (Kidney Cancer Cohort)

  Up to 2 years after completion of study treatment

• Progression-free survival (PFS) (Kidney Cancer Cohort)

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

• Tumor volume changes (Uterine Fibroids Cohort)

  Up to 1 year

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

  Baseline up to 1 year

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

  Baseline up to 1 year

Study Arms (1)

Treatment (6-MP)

EXPERIMENTAL

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

Mercaptopurine DRUG

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

Treatment (6-MP)

Biospecimen Collection PROCEDURE

Undergo collection of blood

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

Treatment (6-MP)

Computed Tomography PROCEDURE

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

Treatment (6-MP)

Magnetic Resonance Imaging PROCEDURE

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

Treatment (6-MP)

Questionnaire Administration OTHER

Ancillary studies

Treatment (6-MP)

Skin Biopsy PROCEDURE

Undergo skin biopsy

Also known as: Biopsy of Skin

Treatment (6-MP)

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (6-MP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• The V Foundation: collaborator
• Phase One Foundation: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Hereditary leiomyomatosis and renal cell cancer; Carcinoma, Renal Cell; Myofibroma

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Mercaptopurine; azathiopurine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Brian Shuch

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2034
• Study Completion (Estimated): December 1, 2035
• Last Updated: July 21, 2026

Record last verified: 2026-07

Locations

US (1)