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Sirolimus for the Treatment of Metastatic Mismatch Repair Deficient Solid Tumors after Progression on Immunotherapy

Trial Status: Active

This phase II trial studies the effect of sirolimus in treating mismatched repair deficient solid tumors that have spread to other places in the body (metastatic) and have been previously treated with immunotherapy (which is standard of care). Sirolimus is used to decrease the body's immune response and may increase blood cell counts. Giving sirolimus may work better in treating patients with solid tumors that lack a molecular system required to correct errors in deoxyribonucleic acid (DNA) (mismatch-repair deficient tumors).

Inclusion Criteria

  • Metastatic solid cancer tumor after immunotherapy (either due to progression of disease or inability to tolerate treatment)
  • dMMR by immunohistochemistry (IHC) defined as the loss of expression in any of the four major MMR proteins (MLH1, MSH2, MSH6 and PMS2) or by next generation sequencing (NGS)
  • Age older than 18 at the time of informed consent
  • Eastern Cooperative Oncology Group performance status of 0-2
  • >= 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
  • Absolute neutrophil count (ANC) >= 1,500 mm^3
  • Platelet count >= 75,000 mm^3
  • Hemoglobin >= 9 g/dl
  • Aspartate aminotransferase (AST) =< 3.0 times the upper normal limit (UNL)
  • Alanine aminotransferase (ALT) =< 3.0 times the upper normal limit (UNL)
  • Bilirubin =< 1.5 times the UNL
  • Serum creatinine =< 1.5 times the UNL

Exclusion Criteria

  • Received immunotherapy in the prior 21 days
  • Have not recovered from toxicities of prior treatments to at least grade 1
  • Symptomatic central nervous system (CNS) metastases
  • Pregnancy or breast-feeding

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: ACTIVE
Contact: Sanjay Goel
Phone: 718-405-8404

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of sirolimus by estimating the overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients with metastatic mismatch repair deficiency (dMMR) solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment).

SECONDARY OBJECTIVES:

I. To assess potential tissue biomarkers (Akt, pAkt, FOXO3a, pFOXO3a, 8OxoG expression by immunohistochemistry, tumor mutational burden/gene mutations by next-generation sequencing), the effect of sirolimus treatment on these biomarkers, and possible correlation between these biomarkers and clinical response.

II. To evaluate other clinical end-points such as progression-free survival, response duration and overall survival of sirolimus in patients with metastatic dMMR solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment).

III. To evaluate tolerability and safety of sirolimus using Common Terminology Criteria for Adverse Events (CTCAE) grading scale.

OUTLINE:

Patients receive sirolimus orally (PO) daily on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT after 8, 16, and 24 weeks of treatment. Patients may continue sirolimus treatment in the absence of disease progression or unacceptable toxicity if disease is controlled during imaging.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Montefiore Medical Center-Weiler Hospital

Principal Investigator
Sanjay Goel

  • Primary ID 2019-10724
  • Secondary IDs NCI-2021-00208
  • Clinicaltrials.gov ID NCT04393454