Alisertib for Rhabdoid Tumors

(SJATRT Trial)

Not currently recruiting at 9 trial locations

Overseen By Tabatha E. Doyle, RN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Enzyme inducers

Disqualifiers: Uncontrolled infection, Sleep apnea, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 35

Duration: Up to 105 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether alisertib, a drug that inhibits the protein Aurora A, can help treat children with certain aggressive and rare rhabdoid tumors. The study targets individuals under 22 years old with tumors that have either returned, not responded to previous treatments, or are newly diagnosed. It tests alisertib alone or in combination with chemotherapy and radiation to determine its effectiveness in controlling the cancer. Ideal candidates are children with a confirmed diagnosis of atypical teratoid rhabdoid tumors (AT/RT) or malignant rhabdoid tumors (MRT) who have not previously received alisertib. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like enzyme-inducing antiepileptic drugs or St. John's wort within 7 days before starting alisertib. It's best to discuss your current medications with the study team.

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

Research shows that alisertib, when used alone, is generally safe for children with rare tumors such as atypical teratoid rhabdoid tumors (AT/RT) and malignant rhabdoid tumors (MRT). Studies have found that although children taking alisertib experienced some side effects, these were manageable.

While alisertib hasn't been effective in every study, its safety record remains encouraging. This suggests that although it might not work for everyone, it is safe enough for ongoing trials. Researchers are also testing alisertib alongside chemotherapy and radiation, which are common cancer treatments.

These findings suggest that alisertib could be a safe option for more children, but further research is needed to fully understand its safety and effectiveness. For those considering joining a clinical trial, knowing that alisertib has been well-tolerated in past studies may provide reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for rhabdoid tumors?

Unlike the standard of care for rhabdoid tumors, which typically involves extensive chemotherapy and radiation, Alisertib offers a fresh angle by specifically inhibiting a protein called Aurora A kinase, which is crucial for cell division. This targeted approach may lead to more effective tumor control with potentially fewer side effects. Researchers are excited because Alisertib, both alone and in combination with other treatments, could offer new hope, especially for patients with recurrent or hard-to-treat forms of rhabdoid tumors.

What evidence suggests that alisertib could be an effective treatment for rhabdoid tumors?

Research has shown that alisertib, a type of drug, may help treat rhabdoid tumors. In studies with children who have recurring AT/RT, about one-third experienced either no tumor growth or a slight reduction in tumor size when taking alisertib alone. This indicates that the treatment stopped the tumor from growing or made it smaller in some patients. Evidence also suggests that these positive effects lasted for a significant time. In this trial, some participants will receive alisertib alone, while others will receive it in combination with chemotherapy and radiation therapy. Due to these findings, researchers are further studying alisertib as a possible treatment for rhabdoid tumors in young patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Amar Gajjar, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for patients under 22 years old with rhabdoid tumors, including AT/RT or MRT. They must have a confirmed diagnosis and measurable disease or tumor cells in CSF. Participants need proper organ function, no prior alisertib treatment, and a life expectancy over 8 weeks. Females of childbearing age must test negative for pregnancy and agree to birth control use.

Inclusion Criteria

I have been recently diagnosed with AT/RT.

My tumor lacks INI1 or BRG1, confirmed by tests.

My neurological condition is stable, and I've been on a consistent dose of corticosteroids for over a week.

Exclusion Criteria

Other severe acute or chronic medical or psychiatric condition that would make the patient inappropriate for enrollment in this study

Clinically significant medical disorders that could compromise the ability to tolerate protocol therapy or that would interfere with the study procedures or results history

Patients who are receiving other investigational drugs 14 or fewer days before enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Alisertib is administered as a single agent or in combination with chemotherapy and radiation therapy, depending on the stratum. For recurrent patients, alisertib is given on days 1-7 of each 21-day cycle.

Up to 105 weeks

35 cycles of 3 weeks each

Follow-up

Participants are monitored for safety and effectiveness after treatment, with progression-free survival and overall survival being key measures.

Up to 5 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they show sustained response or stabilization.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Alisertib

Trial Overview The study tests alisertib's effectiveness on pediatric patients with recurrent or newly diagnosed rhabdoid tumors. It will be given alone or with chemotherapy/radiation depending on the patient's condition and age. The trial aims to measure response rates, progression-free survival (PFS), overall survival (OS), drug toxicity, local/distant failure patterns, and pharmacokinetics.

How Is the Trial Designed?

Group I: (C) Alisertib, chemotherapy, radiation therapy Experimental Treatment 6 Interventions

Stratum C: Children ≥36 months old with newly diagnosed AT/RT. Participants with synchronous extraneural AT/RT (Stratum D4) will also be treated as those assigned to Stratum C. Interventions: Craniospinal radiation therapy; followed by consolidation chemotherapy using alisertib, vincristine, cisplatin (or carboplatin), cyclophosphamide; followed by maintenance alisertib, surgical resection, if indicated.

Group II: (B) Alisertib, chemotherapy, radiation therapy Experimental Treatment 10 Interventions

Stratum B: Children \< 36 months old with newly diagnosed AT/RT. AT/RT those with synchronous extraneural AT/RT (Stratum D1) may also be treated on this arm. Interventions: * B1 or D1: Induction chemotherapy using methotrexate, vincristine, cisplatin (or carboplatin), cyclophosphamide; followed by focal radiation therapy; followed by induction therapy using alisertib, vincristine, cisplatin (or carboplatin), cyclophosphamide; followed by maintenance alisertib. Those \<12 months who are not ready for focal radiation therapy will receive consolidation chemotherapy using alisertib, cyclophosphamide, carboplatin and etoposide while RT is delayed. Surgical resection, if indicated. * B2, B3, D2 or D3: Induction chemotherapy using alisertib, vincristine, cisplatin (or carboplatin), cyclophosphamide; followed by consolidation with topotecan and cyclophosphamide or optional craniospinal irradiation; followed by maintenance alisertib. Surgical resection, if indicated.

Group III: (A) Alisertib alone Experimental Treatment 2 Interventions

Stratum A: Patients with recurrent/progressive AT/RT or extra-CNS malignant rhabdoid tumors (MRT). Interventions: alisertib, 35 cycles of 3 weeks each (up to 105 weeks). Surgical resection, if indicated.

Alisertib is already approved in United States, European Union for the following indications:

Approved in United States as Alisertib for:

• Acute myeloid leukemia (AML)

Approved in European Union as Alisertib for:

• None approved; under investigation for various cancers

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Takeda Pharmaceuticals U.S.A., Inc.

Collaborator

Trials

1

Recruited

130+

Millennium Pharmaceuticals, Inc.

Industry Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Published Research Related to This Trial

In a phase I study involving 45 patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, the combination of alisertib with rituximab was found to be well tolerated, with a recommended phase II dose of 50 mg b.i.d. for alisertib alone and 40 mg b.i.d. when combined with vincristine.

The treatment showed promising efficacy, particularly in non-germinal center diffuse large B-cell lymphoma, with 45% of patients responding at the recommended dose, including complete and partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma. Kelly, KR., Friedberg, JW., Park, SI., et al.[2020]

In a phase I trial involving 10 postmenopausal patients with endocrine-resistant ER+ metastatic breast cancer, the combination of alisertib and fulvestrant was well tolerated, with no severe toxicities reported during the first treatment cycle.

The treatment showed promising antitumor activity, with a median progression-free survival of 12.4 months and a 6-month clinical benefit rate of 77.8%, indicating potential effectiveness even in patients who had previously progressed on fulvestrant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer. Haddad, TC., D'Assoro, A., Suman, V., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9925713/

Phase II study of alisertib as a single agent for treating ... Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35652336/

Phase II study of alisertib as a single agent for treating ... Single-agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02114229

Phase 2 Study of Alisertib Therapy for Rhabdoid Tumors This study incorporates alisertib, the small-molecule inhibitor of Aurora A activity, in the treatment of patients younger than 22 years of age.

4. academic.oup.com academic.oup.com/noa/article/4/1/vdac090/6603574

Sustained and durable response with Alisertib monotherapy in ... Sustained and durable response with Alisertib monotherapy in the treatment of relapsed Atypical Teratoid Rhabdoid Tumor (ATRT) Open Access · Case Report.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1476558623000052

Recent progress and novel approaches to treating atypical ... We here review prior AT/RT clinical trials and highlight promising pre-clinical results that may inform novel clinical approaches to this aggressive cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6897379/

A Phase 2 Study of Alisertib in Children with Recurrent ... We conducted a phase 2 trial of alisertib in pediatric patients with refractory or recurrent solid tumors or acute leukemias.

7. cancer.gov cancer.gov/clinicaltrials/NCI-2014-00901

Alisertib Alone or in Combination with Chemotherapy and ... Giving alisertib alone or with chemotherapy and radiation therapy may be effective in treating patients with rhabdoid tumors. Eligibility Criteria. Inclusion ...

8. academic.oup.com academic.oup.com/neuro-oncology/article/17/6/882/1115214

Alisertib is active as single agent in recurrent atypical teratoid ... Malignant rhabdoid tumors (MRTs) are rare, highly aggressive tumors that occur in young children, which were initially reported in association ...