Abemaciclib + Temozolomide for Brain Tumors

Recruiting at 63 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

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

Trial Summary

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. ^{1 2 3 4 5}

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. ^{1 6 7 8 9}

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. ^{1 3 5 10 11}

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.

Research Team

Contact Lilly at 1-800-LillyRx (1-800-545-5979)

Principal Investigator

Eli Lilly and Company

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

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]

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 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]

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 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]

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]

References

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

Future directions for temozolomide therapy. [2019]

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

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. [2023]

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]

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]

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]

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

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]

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

Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. [2018]

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]

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

Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study. [2018]

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]

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

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018]