Abemaciclib + Temozolomide for Brain Tumors

Recruiting in Palo Alto (17 mi)

+59 other locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Eli Lilly and Company

Must be taking: Temozolomide

Must not be taking: ALK inhibitors, BRAF inhibitors, NTRK inhibitors

Disqualifiers: Diffuse intrinsic pontine glioma, recurrent HGG, secondary HGG, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure the benefit of adding abemaciclib to the chemotherapy, temozolomide, for newly diagnosed high-grade glioma following radiotherapy. Your participation could last approximately 11 months and possibly longer depending upon how you and your tumor respond.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, any current systemic steroid use must be stable or decreasing at least 7 days before starting the trial.

What data supports the effectiveness of the drug combination Abemaciclib and Temozolomide for brain tumors?

Temozolomide has shown effectiveness in treating high-grade gliomas and glioblastoma multiforme, especially when used with radiation therapy. Additionally, it has been evaluated in combination with other drugs for brain metastases, indicating its potential in treating various brain tumors.

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Is the combination of Abemaciclib and Temozolomide safe for humans?

Temozolomide is generally well-tolerated, with common side effects like fatigue, nausea, and low blood cell counts. Severe blood-related side effects are rare. No specific safety data for the combination with Abemaciclib is provided, but Temozolomide alone has been studied for safety in various conditions.

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What makes the drug combination of Abemaciclib and Temozolomide unique for treating brain tumors?

The combination of Abemaciclib and Temozolomide is unique because it pairs a targeted therapy (Abemaciclib, which inhibits specific proteins involved in cancer cell growth) with an oral chemotherapy drug (Temozolomide, which damages the DNA of cancer cells), potentially offering a novel approach to treating brain tumors by attacking the cancer in two different ways.

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Eligibility Criteria

This trial is for young individuals with a high-grade glioma, a type of brain tumor, who have completed radiotherapy. The study aims to see if adding abemaciclib to standard chemotherapy (temozolomide) after radiation can be beneficial.

Inclusion Criteria

My biopsy shows I have a high-grade brain tumor (Grade 3-4).

Contraceptive use consistent with local regulations

I started radiotherapy within the required time frame.

Exclusion Criteria

Current enrollment in another incompatible trial

Preexisting medical condition(s) precluding study participation

Pregnant, breastfeeding, or intend to become pregnant during the study

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

Participants receive radiotherapy as part of the initial treatment for high-grade glioma

6 weeks

Treatment

Participants receive either temozolomide monotherapy or a combination of abemaciclib and temozolomide

11 months

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Participant Groups

The study compares the effectiveness of two treatments: one group receives temozolomide alone, while the other group gets both temozolomide and abemaciclib. Participants will be monitored for about 11 months or more depending on their response.

Group I: Abemaciclib + Temozolomide - Arm A Experimental Treatment 2 Interventions

Participants will receive abemaciclib administered orally in addition to temozolomide administered orally or intravenously (IV).

Group II: Temozolomide - Arm B Active Control 1 Intervention

Participants will receive temozolomide administered orally or IV.

Abemaciclib is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

🇪🇺 Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Phoenix Children's Hospital Phoenix, AZ

Lucile Packard Children's Hospital Palo Alto, CA

Childrens National Medical Center Washington, United States

Spectrum Health Grand Rapids, MI

More Trial Locations

Who Is Running the Clinical Trial?

Eli Lilly and Company Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. [2019] Although the initial indications of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) therapy are for refractory central nervous system malignancies (anaplastic astrocytoma in the United States and Europe, glioblastoma multiforme in Europe), a number of clinical trials are planned or ongoing to evaluate the efficacy and safety of temozolomide in newly diagnosed glioma, oligodendroglioma, pediatric glioma, brain metastases, metastatic melanoma, and other systemic tumors. Also under investigation are modifications to the temozolomide dosing schedule, other routes of administration, and treatment regimens that include temozolomide in combination with other chemotherapeutic and biologic agents. Temozolomide has the potential to be a useful agent in the treatment of a variety of cancers.

2. United States pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. [2023] Label="OBJECTIVES" NlmCategory="OBJECTIVE">To report on the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma METHODS: Single-center retrospective series of glioma patients treated with olaparib/TMZ September 2018-December 2021 RESULTS: Twenty patients (median age: 42, median Karnofsky Performance Status: 90) received olaparib/TMZ for diagnoses of IDH-mutant oligodendroglioma (n=5), IDH-mutant astrocytoma grade 2-3 (n=4), IDH-mutant astrocytoma grade 4 (n=7), or IDH-wildtype glioma (n=4). One patient was treated upfront and 19 at recurrence (median=3). Olaparib 150mg was administered three times/week concurrent with TMZ 50-75mg/m2 daily. Fatigue, gastrointestinal symptoms, and hematologic toxicity were common. 6/20 patients required dose reduction (n=4) or discontinuation (n=2) due to toxicity. Radiographic response was evaluable in 16 and observed (complete + partial) in 4/8 with IDH-mutant grade 2-3 glioma. No responses were seen in patients with grade 4 IDH-mutant astrocytomas (0/5) or IDH-wildtype gliomas (0/3). Progression-free survival was 7.8, 1.3, and 2.0 months, respectively.

3. United States pubmed.ncbi.nlm.nih.gov

Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. [2022] Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM.

4. New Zealand pubmed.ncbi.nlm.nih.gov

A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of Temozolomide 200&#160;mg/m2 (Dralitem&#174; vs. Temodal&#174; Capsules) in Patients with Primary Tumors of the Central Nervous System Under Fasting Conditions. [2018] Temozolomide is an antineoplastic agent of proven efficacy against high-grade gliomas.

5. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. [2018] A combination regimen of temozolomide (TMZ) and pegylated liposomal doxorubicin has been evaluated in the treatment of brain metastases from solid tumours.

6. England pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022] Temozolomide (TMZ) is an oral alkylating agent principally indicated for neurological malignancies including glioblastoma (GBM) and astrocytoma. Most common side effects are mild to moderate, and include fatigue, nausea, vomiting, thrombocytopenia and neutropenia. Severe or prolonged myelosuppression, causing delayed treatment or discontinuation, is uncommon. Major haematological adverse effects such as myelodysplastic syndrome or aplastic anaemia (AA) have rarely been reported.

7. United States pubmed.ncbi.nlm.nih.gov

Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. [2018] Temozolomide is a well-tolerated oral alkylating agent with activity in the CNS. A multicenter, open-label, phase II study was conducted to assess the safety and efficacy of temozolomide in patients with brain metastases from metastatic melanoma (MM) who did not require immediate radiotherapy.

8. United States pubmed.ncbi.nlm.nih.gov

Phase I study of vorinostat in combination with temozolomide in patients with high-grade gliomas: North American Brain Tumor Consortium Study 04-03. [2021] A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG).

9. United States pubmed.ncbi.nlm.nih.gov

Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study. [2018] Temozolomide plus thalidomide is a promising oral combination regimen for the treatment of metastatic melanoma. The current Phase II study examined the efficacy and safety of this combination in chemotherapy-naive patients with brain metastases.

10. United States pubmed.ncbi.nlm.nih.gov

Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. [2022] Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy.

11. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018] Continuous research into new strategies and chemotherapy agents for the treatment of malignant high-grade gliomas have led to the synthesis of a new chemotherapy drug, temozolomide (TMZ), with a lower toxicity profile compared to conventional chemotherapy agents, such as nitrosoureas. Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high-grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability, TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM. We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ, followed by six cycles of adjuvant chemotherapy with TMZ, in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only.