Abemaciclib + Temozolomide for Brain Tumors

Recruiting at 124 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: < 65

Sex: Any

Trial Phase: Phase 2

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 11 months

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the drug abemaciclib, a CDK4/6 inhibitor, to the standard chemotherapy treatment, temozolomide, benefits people with newly diagnosed high-grade glioma, a type of brain tumor, after radiotherapy. Participants will be divided into two groups: one will receive only temozolomide, while the other will receive both abemaciclib and temozolomide. The trial seeks individuals diagnosed with specific types of high-grade gliomas. Those recently diagnosed with a high-grade glioma and who have completed radiotherapy may find this trial suitable. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abemaciclib can safely reach the brain and target certain proteins to slow tumor growth. Studies have found that patients usually tolerate abemaciclib well, with manageable side effects. Common side effects include tiredness and nausea, typical of many cancer treatments.

Temozolomide, a chemotherapy drug approved by the FDA for treating brain tumors, has a well-established safety profile. It is generally well-tolerated, though some patients might experience side effects like low blood counts or tiredness.

Researchers are studying whether abemaciclib and temozolomide work better together against brain tumors. Other studies have focused on the safety of this combination, and results suggest it is generally safe, with side effects similar to those seen with each drug alone. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain tumors?

Researchers are excited about combining Abemaciclib with Temozolomide for brain tumors because it offers a fresh approach to treatment. Unlike traditional therapies that primarily rely on Temozolomide alone, this combination introduces Abemaciclib, a CDK4/6 inhibitor, which targets cancer cell growth at a different level. Abemaciclib works by blocking proteins that drive the division of cancer cells, potentially enhancing the effectiveness of Temozolomide. This dual approach could offer a new avenue for tackling brain tumors more aggressively and effectively.

What evidence suggests that this trial's treatments could be effective for brain tumors?

This trial will compare the effectiveness of two treatment approaches for brain tumors. Participants in one arm will receive temozolomide alone. Studies have shown its effectiveness, with 52.6% of patients experiencing tumor shrinkage in certain types of brain tumors. In another arm, participants will receive a combination of abemaciclib and temozolomide. Early findings suggest that adding abemaciclib could enhance temozolomide's effectiveness, significantly improving survival in some brain tumors. While more research is needed, these early results offer encouragement for those considering this treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Temozolomide

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a phase II trial involving 38 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a high response rate, with 52.6% of patients showing a complete or partial response, indicating its efficacy as a first-line chemotherapy.

TMZ was generally well tolerated, with hematologic side effects being the most common, and only one patient discontinuing treatment due to toxicity, suggesting a favorable safety profile for chemotherapy-naive patients.

NCBI (Pubmed)

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. van den Bent, MJ., Taphoorn, MJ., Brandes, AA., et al.[2022]

Temozolomide, an oral chemotherapy drug, was found to be well tolerated in patients with brain metastases from metastatic melanoma, with only 3% of patients discontinuing treatment due to adverse effects.

In a study of 151 patients, temozolomide showed some efficacy, with 7% of previously untreated patients achieving an objective response and 29% having stable disease, although the median overall survival was 3.5 months for untreated patients and 2.2 months for those previously treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. Agarwala, SS., Kirkwood, JM., Gore, M., et al.[2018]

The combination of temozolomide and radiation therapy is safe and well tolerated in patients with newly diagnosed glioblastoma, with only mild to moderate nonhematologic toxicities observed during treatment.

Patients treated with this regimen had a median survival of 16 months, with 58% surviving at one year and 31% at two years, indicating that this treatment may effectively prolong survival, especially in younger patients and those who had surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. Stupp, R., Dietrich, PY., Ostermann Kraljevic, S., et al.[2022]

In a phase II clinical trial involving 21 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy resulted in a one-year survival rate of 58% and a median survival time of 15.7 months, indicating its efficacy in extending survival.

The treatment regimen was well-tolerated, with only mild to moderate non-hematological side effects and minimal severe hematological toxicity, suggesting that TMZ has a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Lanzetta, G., Campanella, C., Rozzi, A., et al.[2018]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

In a phase II trial involving 19 patients, the combination of temozolomide (TMZ) and pegylated liposomal doxorubicin showed an overall response rate of 36.8%, with three patients achieving a complete response and four a partial response, indicating promising efficacy in treating brain metastases from solid tumors.

The treatment was well tolerated, with manageable toxicities, and resulted in a median overall survival of 10.0 months and a median progression-free survival of 5.5 months, along with significant improvements in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. Caraglia, M., Addeo, R., Costanzo, R., et al.[2018]

A study involving 16 patients with primary CNS tumors demonstrated that Dralitem® capsules of temozolomide are bioequivalent to the reference product, Temodal®, meaning they are absorbed in the body at similar rates and extents under fasting conditions.

The most common side effects reported were mild, including vomiting and abdominal pain, with no serious adverse events, indicating that Dralitem® is a safe alternative to Temodal® for treating high-grade gliomas.

NCBI (Pubmed)

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. Muggeri, A., Vago, M., Pérez, S., et al.[2018]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

In a Phase II study involving 26 chemotherapy-naive patients with brain metastases from metastatic melanoma, the combination of temozolomide and thalidomide showed activity, with 12% of patients achieving a complete or partial response in brain tumors.

The treatment was associated with significant safety concerns, as 11 patients discontinued due to serious adverse events, including intracranial hemorrhage and pulmonary embolism, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study. Hwu, WJ., Lis, E., Menell, JH., et al.[2018]

In a study of 20 patients with various types of glioma, the combination of olaparib and temozolomide (TMZ) showed a 50% objective radiographic response rate in patients with recurrent IDH-mutant grade 2-3 gliomas, indicating potential efficacy for this specific group.

While the treatment was generally manageable, common side effects included fatigue and gastrointestinal issues, with 30% of patients requiring dose adjustments due to toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. Schaff, LR., Kushnirsky, M., Lin, AL., et al.[2023]

The maximum tolerated dose (MTD) of vorinostat when combined with temozolomide (TMZ) was determined to be 500 mg daily in the first part of the study, with dose-limiting toxicities including severe anorexia and thrombocytopenia.

Vorinostat was found to be well tolerated in patients with high-grade glioma, showing no significant pharmacokinetic interactions with TMZ, and it effectively caused hyperacetylation of histones, indicating its mechanism of action.

NCBI (Pubmed)

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. Lee, EQ., Puduvalli, VK., Reid, JM., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04238819

NCT04238819 | A Study of Abemaciclib (LY2835219) in ... The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.

2. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=22-C-0003&&query=Adult%20Brain%20Glioma

NIH Clinical Center: Search the Studies To see if researchers can measure how much abemaciclib is in a person's brain tumor and brain fluid after they take the drug for a few days. Eligibility: People ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-01113

Abemaciclib for the Treatment of Patients with Recurrent ... This phase I clinical trial investigates whether it is possible to safely measure how much of the anti-cancer drug, abemaciclib remains in the brain tumor ...

4. withpower.com withpower.com/trial/abemaciclib-temozolomide-for-brain-tumors-c6986

Abemaciclib + Temozolomide for Brain Tumors In a phase II trial involving 38 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a high response rate, with 52.6% of patients ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2073

Combining abemaciclib, temozolomide, and radiation in ... Our study demonstrates that the combination of Abemaciclib, TMZ, and XRT offers a novel, synergistic approach for DIPG, significantly improving survival in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02981940

A Study of Abemaciclib in Recurrent Glioblastoma In laboratory studies, Abemaciclib was able to enter the brain, stop CDK 4 and CDK 6 from making cells, and slow growth of mice Glioblastoma. In this research ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/26/20/5310/82934/A-Phase-II-Study-of-Abemaciclib-in-Patients-with

A Phase II Study of Abemaciclib in Patients with Brain ... Secondary outcomes included additional intra- and extracranial outcomes, as well as the safety and pharmacokinetics of abemaciclib and its metabolites.