Clinical Trials /

Study to Evaluate the Efficacy and Safety of Sirolimus in Subjects With Metastatic, Mismatch Repair Deficient Solid Tumors After Immunotherapy

NCT04393454

Description:

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 dMMR solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04393454

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Efficacy and Safety of Sirolimus in Subjects With Metastatic, Mismatch Repair Deficient Solid Tumors After Immunotherapy
  • Official Title: Phase II Study to Evaluate the Efficacy and Safety of Sirolimus in Subjects With Metastatic, Mismatch Repair Deficient Solid Tumors After Immunotherapy

Clinical Trial IDs

  • ORG STUDY ID: 2019-10724
  • NCT ID: NCT04393454

Conditions

  • Metastatic dMMR Solid Cancer
  • Solid Tumor
  • Cancer
  • Metastatic Solid Tumor

Interventions

DrugSynonymsArms
Sirolimus 2Mg TabSirolimus

Purpose

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 dMMR solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment).

Detailed Description

      Despite recent therapeutic strategies, including immunotherapy, treatment alternatives for
      patients with metastatic mismatch-repair deficient (dMMR) solid tumors remain scarce.
      Pre-clinical data suggests that dMMR tumors are susceptible to rapamycin (sirolimus), a mTOR
      inhibitor. In these tumors, characterized by higher levels of oxidative stress, sirolimus can
      exert a cytotoxic effect, led by the failure to repair DNA damage by inhibition of
      antioxidant enzymes such as FOXO3a triggered by Akt hyperactivation.

      This proposal presents a phase 2 clinical trial designed to evaluate the efficacy of
      sirolimus in patients with dMMR solid tumors after immunotherapy. The investigators
      hypothesize that sirolimus will increase the overall response rate (ORR) by 20%.

Trial Arms

NameTypeDescriptionInterventions
SirolimusExperimentalParticipants will be instructed to take 2 mg every day for 28 days (1 cycle). They will be evaluated in the oncology clinic every 2 weeks to make sure they are tolerating the medication well.
  • Sirolimus 2Mg Tab

Eligibility Criteria

        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 RECIST, version 1.1 (16)

          -  Absolute neutrophil count (ANC) ≥1,500 mm3

          -  Platelet count ≥75,000 mm3

          -  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.
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:6 months
Safety Issue:
Description: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 dMMR solid cancer after immunotherapy (either due to disease progression or to inability to tolerate treatment).

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) - median months
Time Frame:6 months
Safety Issue:
Description: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).
Measure:Response Duration (months)
Time Frame:6 months
Safety Issue:
Description: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).
Measure:Overall Survival (OS) - median months
Time Frame:6 months
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Albert Einstein College of Medicine

Last Updated

May 20, 2021