Temsirolimus Infusion for Brain Tumor
Recruiting in Palo Alto (17 mi)
Overseen byNader Sanai, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Nader Sanai
Disqualifiers: Interstitial lung disease, Pregnancy, others
No Placebo Group
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a single-center, open-label, dose-escalating Phase 0 trial that will enroll participants with a confirmed diagnosed recurrent high-grade glioma (grade 3 or 4 per WHO criteria) targeting the mTOR pathway. Eligible participants will be administered a single infusion of temsirolimus through super-selective intra-arterial infusion or intravenous infusion. Participants will receive the study drug administration on the same day as the planned surgical resection of the tumor.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, if you are on another investigational drug, you must stop it at least 30 days before starting the trial treatment.
What data supports the effectiveness of the drug Temsirolimus for brain tumors?
Temsirolimus, an mTOR inhibitor, has shown promise in treating various cancers, including breast cancer and renal cell carcinoma, with response rates of 10-20% in some studies. It is also being evaluated for melanoma and has shown effectiveness in mantle-cell lymphoma with a 40% response rate.
12345Is temsirolimus safe for humans?
Temsirolimus has been studied in various clinical trials, showing some side effects like rash, mouth sores, and fatigue. In combination with other drugs, it can cause low platelet counts, which are cells that help blood clot. The maximum tolerated dose varies depending on the formulation and combination with other treatments.
12467How is the drug Temsirolimus unique for treating brain tumors?
Temsirolimus is unique because it is an mTOR inhibitor, which means it blocks a specific protein that helps cancer cells grow. It is given through an infusion (a slow injection into a vein) and is being studied for its potential to treat brain tumors, which is different from many standard treatments that might not target this specific pathway.
12589Eligibility Criteria
Adults over 18 with a specific type of brain tumor called high-grade glioma that's come back after initial treatment can join. They must have completed the Stupp regimen, not be pregnant or able to become pregnant, and agree to use effective contraception. People with serious medical conditions like active infections or lung disease, recent other trials, or live vaccinations are excluded.Inclusion Criteria
My cancer shows specific genetic changes related to mTOR signaling.
My bone marrow and organs are functioning well.
I have a tumor that can be measured and is at least 1 cm in size.
+11 more
Exclusion Criteria
Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, active infection, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance]
Pregnancy or lactation
Known hypersensitivity to temsirolimus or its metabolites, polysorbate 80, or to any other component of temsirolimus
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a single infusion of temsirolimus via super-selective intra-arterial infusion or IV on the same day as the planned surgical resection of the tumor
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
This trial tests Temsirolimus delivered directly into the artery feeding the tumor or through an IV on the same day as surgery to remove the tumor. It's for those whose tumors show certain changes in their mTOR pathway and is designed to find out how different doses affect patients.
1Treatment groups
Experimental Treatment
Group I: Single infusion of TemsirolimusExperimental Treatment1 Intervention
Single infusion of Temsirolimus via super-selective intra-arterial infusion or IV
Temsirolimus is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Torisel for:
- Renal cell carcinoma
🇺🇸 Approved in United States as Torisel for:
- Advanced renal cell carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
St. Joseph's Hospital and Medical CenterPhoenix, AZ
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Who Is Running the Clinical Trial?
Nader SanaiLead Sponsor
Barrow Neurological InstituteCollaborator
Ivy Brain Tumor CenterCollaborator
References
A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. [2014]Patients with advanced cancer received temsirolimus (Torisel, CCI-779), a novel inhibitor of mammalian target of rapamycin, i.v. once daily for 5 days every 2 weeks to determine the maximum tolerated dose, toxicity profile, pharmacokinetics, and preliminary antitumor efficacy.
A Phase 1 clinical study of temsirolimus (CCI-779) in Japanese patients with advanced solid tumors. [2014]Temsirolimus (CCI-779) is a novel inhibitor of the mammalian target of rapamycin. This Phase 1 study was aimed at investigating the maximum-tolerated dose, toxicity, pharmacokinetics and antitumor activity in Japanese patients with advanced solid tumors.
[Update on clinical activity of CCI779 (temsirolimus), mTOR inhibitor]. [2021]Temsirolimus (CCI779), an intravenous analog of rapamycin, presents immunosuppressive properties and also antiproliferative activity. Its principal target is the mTOR serine/threonin kinase which controls the initiation of the transcription of many ARNm implicated in carcinogenesis. Breast cancers, glioblastoma and renal cell carcinoma were particularly studied with response rates from 10 to 20 %. In haematology, mantle-cell lymphoma is of particular interest because of constitutional activation of cyclin D1 (response rate of 40 %). As a whole these data define temsirolimus as a promising new drug. Current and further developments are based on its association with chemotherapy in a concomitant or sequential way.
Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. [2022]In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated.
Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. [2021]Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor and rapamycin analogue that is approved for treating advanced renal cell carcinoma (RCC). It is being actively evaluated in clinical trials for melanoma. The mTOR inhibitors are also immunosuppressants and are used clinically to prevent rejection following solid-organ transplant. Novel immunotherapies are being actively developed for immunoresponsive tumours, such as RCC and melanoma.
Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer. [2021]An oral formulation of temsirolimus (Torisel), an inhibitor of the mammalian target of rapamycin, was evaluated on an intermittent schedule (once daily for 5 days every 2 weeks) in patients with advanced cancer. The maximum tolerated dose was determined to be 75 mg after dose-limiting toxicities of grade 3 elevated aminotransferases (1 patient) and grade 3 rash (1 patient) occurred with a 100-mg dose. The most common temsirolimus-related adverse events were mucositis, rash/maculopapular rash, and asthenia. Six of 12 patients who received the 75-mg dose required dose reductions due to temsirolimus-related adverse events. Two patients who received 75-mg temsirolimus and did not have dose reductions had minor tumor responses. Relative exposure from contributions of both temsirolimus and sirolimus, the principal metabolite, was 17.9% of the 75-mg dose. Thus, oral temsirolimus, 75 mg administered once daily for 5 days every 2 weeks, was further evaluated in patients with metastatic breast cancer.
Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02. [2023]The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor-β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents.
Temsirolimus in the treatment of mantle cell lymphoma: frequency and management of adverse effects. [2022]Temsirolimus (Torisel) is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). The recommended dosage in this indication (175 mg once weekly for 3 weeks and then 75 mg once weekly as maintenance) is higher than that for renal cell carcinoma; thus, the safety profile is quite different in the two indications. The aim of this review is to examine safety data for temsirolimus in MCL and provide guidance on the incidence and management of adverse events. Medline and EMBASE searches using the search terms 'temsirolimus' and 'mantle cell lymphoma'.
Population pharmacokinetics of temsirolimus and sirolimus in children with recurrent solid tumours: a report from the Children's Oncology Group. [2021]Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR). Pharmacokinetic (PK) characterization of temsirolimus in children is limited and there is no paediatric temsirolimus population PK model available. The objective of this study was to simultaneously characterize the PK of temsirolimus and its metabolite sirolimus in paediatric patients with recurrent solid or central nervous system tumours and to develop a population PK model.