Prexasertib + Chemotherapy for Brain Cancer

Overseen By Tabatha E. Doyle, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: CHK1 inhibitors

Disqualifiers: Heart disease, QTc prolongation, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for medulloblastoma, a type of brain cancer that has returned or isn't responding to treatment. Researchers are examining how well prexasertib works with two chemotherapy drugs—cyclophosphamide (also known as Cytoxan, Neosar, or Endoxan) and gemcitabine (also known as Gemzar)—to determine the best dose and assess its effectiveness in controlling the cancer. The trial is open to individuals with this specific type of brain cancer, particularly if it recurs or resists standard treatments. Participants should have measurable disease and must have previously undergone treatments like chemotherapy or radiation without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not be on any other investigational agents and should have stopped myelosuppressive anticancer chemotherapy at least 3 weeks before enrolling. It's best to discuss your current medications with the trial team.

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

Earlier studies have tested prexasertib with chemotherapy drugs like cyclophosphamide and gemcitabine. These studies examine the safety and manageability of these combinations for patients. Early results indicate that combining prexasertib with these drugs is generally well-tolerated.

Patients have experienced some side effects common with cancer treatments, such as low blood cell counts, which doctors often manage with additional treatments. This close monitoring is essential in these trials.

Since prexasertib is used with cyclophosphamide and gemcitabine, each with its own safety concerns, researchers monitor for any new side effects. Importantly, these studies aim to determine the safest doses for patients, enhancing understanding of how people respond to the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain cancer because they involve prexasertib, a novel inhibitor that targets the DNA damage response in cancer cells. This is different from the standard of care options like temozolomide and radiation, which primarily target rapidly dividing cells. In Stratum A, prexasertib is combined with cyclophosphamide, aiming to enhance the efficacy by potentially sensitizing cancer cells to DNA damage. In Stratum B, prexasertib is paired with gemcitabine, a chemotherapy drug that also disrupts DNA replication. These combinations could lead to more effective treatments by exploiting the cancer cells’ vulnerabilities in new ways.

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

Research shows that prexasertib, combined with chemotherapy drugs like cyclophosphamide or gemcitabine, might help treat medulloblastoma, a type of brain cancer. In this trial, participants will receive either prexasertib with cyclophosphamide or prexasertib with gemcitabine. Prexasertib blocks proteins that aid cancer cells in dividing and repairing, making these cells more susceptible to damage. Early results suggest that combining prexasertib with these chemotherapy drugs can halt tumor growth or even shrink them temporarily. Prexasertib has also shown promise in stopping tumor growth in other cancer studies, indicating potential effectiveness for patients with difficult-to-treat medulloblastoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Giles Robinson, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 1 to less than 25 with recurrent or stubborn Group 3/Group 4 or SHH medulloblastoma brain tumors. They should have measurable disease, be at least three weeks out from chemotherapy, four weeks from radiation, and not on increasing steroids. Participants need a certain level of physical ability and life expectancy, as well as proper organ function. Pregnant women can't join; those who can have kids must use birth control.

Inclusion Criteria

Participants of childbearing or child fathering potential must be willing to use medically acceptable form of birth control during treatment and for 16 weeks after stopping treatment

I am between 1 and 24 years old.

You must have a disease that can be measured or assessed according to the study's rules.

Exclusion Criteria

I have a history of serious heart disease or abnormal heart rhythm.

I do not have any serious health issues that could affect my participation in the study.

You have a history of a heart condition that causes a specific type of heart rhythm problem.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination treatment with prexasertib and either cyclophosphamide or gemcitabine in 28-day cycles

Up to 24 months

Weekly visits during the first cycle, regular intervals thereafter

Dose-limiting toxicity evaluation

Evaluation of dose-limiting toxicity during the first cycle until day 1 of cycle 2

28 days

At least weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year after treatment completion

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Gemcitabine
• Prexasertib

Trial Overview The SJELIOT phase 1 trial tests prexasertib combined with cyclophosphamide (Stratum A) or gemcitabine (Stratum B) in young patients with tough-to-treat brain tumors. It aims to find the safest dose that works and understand how the body processes these drugs while looking for early signs of effectiveness.

How Is the Trial Designed?

Group I: B: prexasertib + gemcitabine Experimental Treatment 4 Interventions

Stratum B: Participants receive combination treatment with gemcitabine given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, gemcitabine may be given on day 16 and prexasertib may be given on day 17.

Group II: A: prexasertib + cyclophosphamide Experimental Treatment 4 Interventions

Stratum A: Participants receive combination treatment with cyclophosphamide given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, cyclophosphamide may be given on day 16 and prexasertib may be given on day 17.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Eli Lilly and Company

Industry 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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04023669

Study Details | NCT04023669 | Evaluation of LY2606368 ... SJELIOT is a phase 1 trial that aims to explore the combination of prexasertib with established DNA-damaging agents used in medulloblastoma to evaluate ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/PMC11184039

MDB-65. RESULTS FROM THE SJ-ELIOT PHASE 1 ... - PubMed A phase 1 trial that explored the combination of the checkpoint kinase inhibitor, prexasertib with the DNA-damaging agents, cyclophosphamide and gemcitabine.

3. withpower.com withpower.com/trial/phase-1-brain-neoplasms-7-2019-f03d9

Prexasertib + Chemotherapy for Brain Cancer SJELIOT is a phase 1 trial that aims to explore the combination of prexasertib with established DNA-damaging agents used in medulloblastoma to evaluate ...

4. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/prexasertib

Prexasertib - an overview | ScienceDirect Topics As shown in Table 12, Prexasertib (LY-2606368) is an effective CHK1 kinase inhibitor with IC50 of <1 nM for CHK1 and 8 nM for CHK2 [75]. Currently, prexasertib ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9090141/

A Phase 1 Study of Prexasertib (LY2606368), a CHK1/2 ... The primary objectives of this pediatric Phase 1 trial were to establish the maximum tolerated dose (MTD) and/or RP2D of prexasertib, and to characterize the ...

6. researchgate.net researchgate.net/publication/381539778_MDB-65_RESULTS_FROM_THE_SJ-ELIOT_PHASE_1_CLINICAL_TRIAL_EVALUATING_PREXASERTIB_LY2606368_IN_COMBINATION_WITH_CYCLOPHOSPHAMIDE_OR_GEMCITABINE_FOR_CHILDREN_AND_ADOLESCENTS_WITH_REFRACTORY_OR_RECURRENT_M

MDB-65. RESULTS FROM THE SJ-ELIOT PHASE 1 ... Conclusions Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11816256/

Advances in the Repurposing and Blood–Brain Barrier ... Everolimus is safe for patients with diffuse midline glioma of the pons and high-grade glioma in combination with other targeted therapies.