Prexasertib + Chemotherapy for Brain Cancer

Recruiting in Palo Alto (17 mi)

Dr. Giles W. Robinson, MD | Memphis, TN ...

Overseen ByGiles Robinson, MD

Age: < 65

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: St. Jude Children's Research Hospital

No Placebo Group

Trial Summary

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).

Eligibility Criteria

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

I am between 1 and 24 years old.

I received my last chemotherapy dose more than 3 weeks ago.

I am between 1 and 24 years old.

My medulloblastoma has come back or is not responding to treatment.

I am of childbearing age and have a negative pregnancy test.

Exclusion Criteria

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

I have been treated with a CHK1 inhibitor before.

I am currently breastfeeding.

I have a history of serious heart disease that is not under control.

Participant Groups

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.

2Treatment groups

Experimental Treatment

Group I: B: prexasertib + gemcitabineExperimental Treatment4 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 + cyclophosphamideExperimental Treatment4 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: