Study to Evaluate the Efficacy and Safety of Sirolimus in Subjects With Metastatic, Mismatch Repair Deficient Solid Tumors After Immunotherapy
کلید واژه ها
خلاصه
شرح
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%.
تاریخ
| آخرین تأیید شده: | 05/31/2020 |
| اولین ارسال: | 05/12/2020 |
| ثبت نام تخمینی ارسال شد: | 05/15/2020 |
| اولین ارسال: | 05/18/2020 |
| آخرین بروزرسانی ارسال شده: | 06/29/2020 |
| آخرین به روزرسانی ارسال شده: | 07/01/2020 |
| تاریخ شروع مطالعه واقعی: | 06/30/2020 |
| تاریخ تخمین اولیه اولیه: | 12/31/2020 |
| تاریخ برآورد مطالعه: | 12/31/2020 |
شرایط یا بیماری
مداخله / درمان
Drug: Sirolimus
فاز
گروههای بازو
| بازو | مداخله / درمان |
|---|---|
| Experimental: Sirolimus 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. | Drug: Sirolimus 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/nmass 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. |
معیارهای صلاحیت
| سنین واجد شرایط تحصیل | 18 Years به 18 Years |
| جنسیت واجد شرایط مطالعه | All |
| داوطلبان سالم را می پذیرد | آره |
| شاخص | 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. |
نتیجه
اقدامات اولیه
1. Overall Response Rate [6 months]
اقدامات ثانویه
1. Progression Free Survival (PFS) - median months [6 months]
2. Response Duration (months) [6 months]
3. Overall Survival (OS) - median months [6 months]
