Temsirolimus Infusion for Brain Tumor

Overseen By Phase 0 Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nader Sanai

Disqualifiers: Interstitial lung disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how temsirolimus affects individuals with recurrent high-grade glioma, a type of brain tumor. Researchers are concentrating on tumors with changes in the mTOR pathway, which influences cell growth. Participants will receive a single infusion of temsirolimus, either directly into an artery or through an IV, on the same day as their planned tumor-removal surgery. The trial seeks individuals with high-grade glioma in the frontal lobe who have completed the Stupp regimen and have tumors meeting specific genetic criteria. As an Early Phase 1 trial, the research focuses on understanding the treatment's effects, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that temsirolimus has been used safely in past studies. Researchers have administered it to patients with advanced cancer to determine the safest dose. These studies help clarify how the body processes the drug and identify potential side effects.

In another study, researchers administered temsirolimus to patients with brain tumors. This study aimed to evaluate the drug's effectiveness and monitor any side effects.

The FDA has already approved temsirolimus for treating certain types of kidney cancer, indicating thorough safety testing for that condition. However, its use for brain tumors remains under investigation.

This trial is in an early phase, focusing primarily on ensuring the drug's safety for participants. Early phase trials typically involve fewer participants and concentrate on determining the correct dose and monitoring side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain tumors, which often involve surgery, radiation, and chemotherapy, Temsirolimus is unique because it targets the mTOR pathway, a crucial driver in tumor cell growth and survival. Researchers are particularly excited about its delivery method; it can be administered via a super-selective intra-arterial infusion, allowing for a higher concentration of the drug to reach the tumor directly. This targeted approach could potentially enhance the treatment's effectiveness while minimizing side effects, setting it apart from more traditional methods.

What evidence suggests that temsirolimus might be an effective treatment for brain tumors?

Research has shown that temsirolimus, the treatment under study in this trial, may help treat brain tumors, including aggressive types like high-grade glioma. One study found that 36% of patients who received temsirolimus had tumors that appeared smaller or less aggressive on scans. This improvement correlated with a longer period before the disease worsened. Temsirolimus blocks the mTOR pathway, which often contributes to tumor growth. It has been particularly effective in tumors with a faulty PTEN gene, a common issue in these cancers. Some early patients have shown encouraging results, with one individual experiencing a partial response for over a year. These findings suggest that temsirolimus could help slow the growth of certain brain tumors. ^{1 2 3 6 7}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

Chief Scientific Officer/Director

Are You a Good Fit for This Trial?

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.

Has voluntarily agreed to participate by giving written informed consent. Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Temsirolimus

Trial Overview 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.

How Is the Trial Designed?

Group I: Single infusion of Temsirolimus Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

Barrow Neurological Institute

Collaborator

Trials

27

Recruited

7,100+

Ivy Brain Tumor Center

Collaborator

Trials

12

Recruited

910+

Published Research Related to This Trial

Temsirolimus is effective for treating relapsed/refractory mantle cell lymphoma (MCL), but it has a different safety profile compared to its use in renal cell carcinoma, with hematological adverse events being the most common but manageable through dose adjustments.

Gastrointestinal toxicities, particularly diarrhea, are frequent but usually mild, and serious adverse events like grade 3 pneumonitis are rare, especially when temsirolimus is used alone rather than in combination with rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temsirolimus in the treatment of mantle cell lymphoma: frequency and management of adverse effects. Bouabdallah, K., Ribrag, V., Terriou, L., et al.[2022]

The combination therapy of sorafenib and temsirolimus was found to have a maximum tolerated dose (MTD) of 800 mg daily for sorafenib and 25 mg weekly for temsirolimus, with grade 3 thrombocytopenia being the main dose-limiting toxicity.

Despite the safety established in the phase I component, the phase II component showed minimal efficacy, with no patients remaining progression-free at 6 months and a median progression-free survival of only 8 weeks, leading to the study's early termination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02. Lee, EQ., Kuhn, J., Lamborn, KR., et al.[2023]

Temsirolimus demonstrated an objective response rate of 9.2% in patients with advanced breast cancer, indicating some level of antitumor activity, particularly in a heavily pretreated population of 109 patients.

The lower dose of 75 mg showed a more tolerable safety profile compared to the higher 250 mg dose, which was associated with increased toxicity, including a notable incidence of grade 3 or 4 depression in 10% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. Chan, S., Scheulen, ME., Johnston, S., et al.[2022]

In a Phase 1 study involving 10 Japanese patients with advanced solid tumors, the maximum-tolerated dose of temsirolimus was determined to be 15 mg/m², with significant toxicities observed at higher doses, including Grade 3 stomatitis and diarrhea.

Temsirolimus demonstrated dose-dependent pharmacokinetics, with peak blood concentrations of both temsirolimus and its active metabolite sirolimus increasing with higher doses, indicating a need for careful dose management in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 clinical study of temsirolimus (CCI-779) in Japanese patients with advanced solid tumors. Fujisaka, Y., Yamada, Y., Yamamoto, N., et al.[2014]

Temsirolimus, an mTOR inhibitor, significantly enhances the anti-tumor effects of cancer vaccines in murine models for renal cell carcinoma and melanoma, indicating its potential as a powerful adjunct in immunotherapy.

The combination of temsirolimus with HSP-based cancer vaccines leads to stronger immune responses, including increased production of interferon-γ and enhanced formation of CD8 memory T cells, suggesting a robust immune-mediated mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. Wang, Y., Wang, XY., Subjeck, JR., et al.[2021]

This study developed the first population pharmacokinetic (PK) model for temsirolimus and its metabolite sirolimus in pediatric patients with recurrent solid tumors, based on data from 19 patients.

The findings indicate that body weight significantly affects the clearance of temsirolimus, which will help in personalizing dosing for children and improving future clinical trial designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of temsirolimus and sirolimus in children with recurrent solid tumours: a report from the Children's Oncology Group. Mizuno, T., Fukuda, T., Christians, U., et al.[2021]

In a study involving 63 patients with advanced cancer, temsirolimus was found to be generally well tolerated, with a maximum tolerated dose established at 15 mg/m²/day for heavily pretreated patients and 19 mg/m²/day for minimally pretreated patients.

The treatment showed promising preliminary antitumor activity, with one patient achieving a confirmed partial response lasting 12.7 months, and several others showing stable disease for over 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. Hidalgo, M., Buckner, JC., Erlichman, C., et al.[2014]

The maximum tolerated dose of oral temsirolimus for patients with advanced cancer was determined to be 75 mg, with some patients experiencing dose-limiting toxicities such as elevated liver enzymes and rash at higher doses.

Despite some adverse events like mucositis and fatigue, two patients showed minor tumor responses at the 75 mg dose, suggesting potential efficacy that warrants further investigation in metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer. Buckner, JC., Forouzesh, B., Erlichman, C., et al.[2021]

Temsirolimus, an intravenous drug that targets the mTOR kinase, shows immunosuppressive and antiproliferative effects, particularly in cancers like breast cancer, glioblastoma, and renal cell carcinoma, with response rates between 10% to 20%.

In mantle-cell lymphoma, temsirolimus has a higher response rate of 40%, indicating its potential effectiveness, especially when used in combination with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Update on clinical activity of CCI779 (temsirolimus), mTOR inhibitor]. Mounier, N., Vignot, S., Spano, JP.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15998902/

Phase II trial of temsirolimus (CCI-779) in recurrent ... - PubMed Radiographic improvement was observed in 36% of temsirolimus-treated patients, and was associated with significantly longer TTP. High levels of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02238496

Perifosine and Torisel (Temsirolimus) for Recurrent ... The purpose of this study is to test the effectiveness of a drug called temsirolimus in combination with a drug called perifosine in treating brain tumors ...

3. withpower.com withpower.com/trial/early-phase-1-high-grade-glioma-hgg-3-2023-ad01b

Temsirolimus Infusion for Brain Tumor The treatment showed promising preliminary antitumor activity, with one patient achieving a confirmed partial response lasting 12.7 months, and several others ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/12/19/5755/192851/A-Phase-I-and-Pharmacokinetic-Study-of

A Phase I and Pharmacokinetic Study of Temsirolimus (CCI ... Temsirolimus inhibited the growth of a variety of tumor cells and was particularly effective in tumors with a defective PTEN gene (27–33). Temsirolimus also was ...

5. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2005.23.622

Phase II Trial of Temsirolimus (CCI-779) in Recurrent ... The goals of this study were to examine the efficacy of temsirolimus in the treatment of patients with recurrent glioblastoma multiforme, to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4348698/

A PHASE 2 CONSORTIUM STUDY - PMC The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/ ...

7. aetna.com aetna.com/cpb/medical/data/800_899/0873.html

Temsirolimus (Torisel) - Medical Clinical Policy Bulletins Hess and colleagues concluded that temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate ...