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

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

SJELIOT is a phase 1 trial that aims to explore the combination of prexasertib with established DNA-damaging agents used in medulloblastoma to evaluate tolerance and pharmacokinetics in recurrent or refractory disease. Additionally, a small expansion cohort will be incorporated into the trial at the combination MTD/RP2D (maximum tolerated dose/recommended phase two dose) to detect a preliminary efficacy signal. Stratum A: Prexasertib and Cyclophosphamide Primary Objectives * To determine the safety and tolerability and estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of combination treatment with prexasertib and cyclophosphamide in participants with recurrent/refractory Group 3 and Group 4 medulloblastoma and recurrent/refractory sonic hedgehog (SHH) medulloblastoma. * To characterize the pharmacokinetics of prexasertib in combination with cyclophosphamide. Secondary Objectives * To estimate the rate and duration of objective response and progression free survival (PFS) associated with prexasertib and cyclophosphamide treatment in this patient population. * To characterize the pharmacokinetics of cyclophosphamide and metabolites. Stratum B: Prexasertib and Gemcitabine Primary Objectives * To determine the safety and tolerability and estimate the MTD/RP2D of combination treatment with prexasertib and gemcitabine in participants with recurrent/refractory Group 3 and Group 4 medulloblastoma. * To characterize the pharmacokinetics of prexasertib in combination with gemcitabine. Secondary Objectives * To estimate the rate and duration of objective response and PFS associated with prexasertib and gemcitabine treatment in this patient population. * To characterize the pharmacokinetics of gemcitabine and gemcitabine triphosphate (only at St. Jude Children's Research Hospital).

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