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).
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
Drug | Synonyms | Arms |
---|
Sirolimus 2Mg Tab | | Sirolimus |
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
Name | Type | Description | Interventions |
---|
Sirolimus | Experimental | Participants 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. | |
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