NCT04393454

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

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Albert Einstein College of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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), an 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%.

Conditions

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

Interventions

Type	Name	Description
DRUG	Sirolimus 2mg Tablet	Sirolimus (oral) will be started at 2 mg daily. Sirolimus dosing will be titrated to meet serum trough levels of \>8 ng/ml, assayed at 7 days after starting a new dose, by chromatography/mass spectrometry. Once adequate serum levels are met (≥8 ng/ml), the same dosing will be continued until progression of disease as evidenced by imaging, or unacceptable toxicity.

Timeline

• Start date: 2020-11-16
• Primary completion: 2023-05-16
• Completion: 2023-05-16
• First posted: 2020-05-19
• Last updated: 2024-07-25
• Results posted: 2024-07-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study