Silmitasertib + Chemotherapy for Recurrent Solid Tumors

Recruiting at 4 trial locations

Overseen By BCC Enroll

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Investigational drugs, Anticancer agents, Statins, Warfarin

Disqualifiers: Uncontrolled infection, Significant organ dysfunction, Gastrointestinal disorders, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days for initial dose determination, followed by up to 2 years of treatment

104 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and optimal dose of an experimental drug, silmitasertib, combined with chemotherapy for treating solid tumors. It targets individuals with certain relapsed or hard-to-treat cancers, such as neuroblastoma and Ewing sarcoma, which have returned or not responded well to standard treatments. Participants should have a history of these specific tumors and have experienced relapse after standard therapy. This trial could be a potential fit for those interested in exploring new treatment options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including other investigational drugs, anticancer agents, Vitamin K antagonists (like warfarin), and statins (a type of cholesterol-lowering medication). If you are on any of these, you will need to stop them before participating.

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

Research has shown that silmitasertib has been tested with other treatments for various cancers. Patients generally tolerate it well when combined with chemotherapy drugs like irinotecan and temozolomide. Researchers have studied these combinations to assess patient responses and determine the safest doses.

In these studies, some patients experienced side effects, but they were often manageable. The FDA granted silmitasertib "orphan drug" status for treating cholangiocarcinoma (bile duct cancer), indicating potential benefits and a good safety profile.

Overall, while still under study, silmitasertib has shown promise in earlier research for being safe when combined with chemotherapy drugs. This suggests it might be well-tolerated by most patients, though individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Silmitasertib is unique because it targets a specific enzyme known as CK2, which plays a crucial role in cancer cell growth and survival. Unlike standard treatments like chemotherapy, which attack rapidly dividing cells generally, Silmitasertib's targeted approach aims to disrupt cancer cell signaling more precisely. Researchers are excited about its potential to enhance the effectiveness of existing chemotherapy drugs, like Irinotecan and Temozolomide, by making cancer cells more susceptible to their effects. This combination could offer a new strategy for treating stubborn cancers like relapsed neuroblastoma and Ewing sarcoma.

What evidence suggests that this trial's treatments could be effective for recurrent solid tumors?

Research has shown that silmitasertib, one of the treatments in this trial, when combined with chemotherapy, yields promising results for certain solid tumors. Studies indicate that this combination may slow tumor growth and improve survival rates in patients with recurrent or hard-to-treat cancers, such as neuroblastoma and Ewing sarcoma. Silmitasertib blocks a protein that aids cancer cell growth, potentially enhancing the effectiveness of chemotherapy. Early findings suggest that patients receiving silmitasertib with chemotherapy have experienced slower tumor progression. However, as with any new treatment, results can vary, and further studies are needed to confirm these effects. ^{1 5 6 7 8}

Who Is on the Research Team?

Chandrika Behura, MD

Principal Investigator

Penn State Health Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young patients under 30 years old initially diagnosed with specific solid tumors like Neuroblastoma, Ewing Sarcoma, Osteosarcoma, Rhabdomyosarcoma, or Liposarcoma that have not responded to treatment or have come back after treatment. Patients must have a confirmed diagnosis and meet certain criteria based on their type of cancer.

Inclusion Criteria

I was diagnosed before turning 30.

My cancer is one of the specified types and has come back or didn’t respond to treatment.

My neuroblastoma has come back or didn't respond to treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive silmitasertib in combination with chemotherapy to establish a recommended dose and test safety and tolerability

21 days for initial dose determination, followed by up to 2 years of treatment

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety, tolerability, and progression-free survival after treatment

2 years plus 30 days

What Are the Treatments Tested in This Trial?

Interventions

• Silmitasertib

Trial Overview The study tests Silmitasertib (a pill) combined with chemotherapy drugs Irinotecan, Temozolomide, and Vincristine in patients with relapsed or refractory solid tumors. It aims to find the right dose of Silmitasertib when used with these chemotherapies and assess its safety and effectiveness against the cancers.

How Is the Trial Designed?

Group I: Phase II- Relapsed/refractory Neuroblastoma Experimental Treatment 3 Interventions

Silmitasertib RP2D twice a day plus Irinotecan and Temozolomide

Group II: Phase II- Relapsed/refractory Ewing sarcoma Experimental Treatment 4 Interventions

Silmitasertib RP2D twice a day plus Vincristine, irinotecan and temozolomide

Group III: Phase I- Dose level 2 Experimental Treatment 4 Interventions

Silmitasertib 800 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide

Group IV: Phase I- Dose level 1 Experimental Treatment 4 Interventions

Silmitasertib 600 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide

Silmitasertib is already approved in United States for the following indications:

Approved in United States as Silmitasertib for:

• Orphan drug status for advanced cholangiocarcinoma
• Rare Pediatric Disease Designation for Neuroblastoma

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

In a phase I/II trial involving 32 patients with K-RAS mutated colorectal cancer, the combination of selumetinib and irinotecan showed promising efficacy, with a 9.7% partial response rate and 51.6% of patients achieving stable disease for at least 4 weeks.

The recommended dose of selumetinib was established at 75 mg twice daily, and while the study was terminated early, the results suggest that further research into MEK inhibitors for treating metastatic colorectal cancer is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer. Hochster, HS., Uboha, N., Messersmith, W., et al.[2022]

In a study of 187 metastatic colorectal cancer patients, those treated with raltitrexed plus S-1 (RS) had a significantly longer overall survival (OS) of 13.4 months compared to 10.1 months for those treated with regorafenib, indicating RS may be a more effective treatment option.

Both treatment regimens showed similar progression-free survival (PFS) rates, but RS had a higher objective response rate (12.8% vs 5.1%) and manageable adverse events, suggesting it is a safe and effective choice for patients with refractory metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of raltitrexed plus S-1 versus regorafenib in patients with refractory metastatic colorectal cancer: a real-world propensity score matching study. Zhou, YW., Wang, JL., Li, QF., et al.[2022]

Regorafenib is an oral multi-kinase inhibitor that has shown significant survival benefits in metastatic colorectal cancer and has been FDA approved for this use since 2012.

The drug also improves progression-free survival in patients with metastatic gastrointestinal stromal tumors and advanced hepatocellular carcinoma, leading to its FDA approval for these conditions as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2018]

The fRida trial, involving 123 patients with untreated metastatic triple-negative breast cancer, found that adding the CXCR1 inhibitor Reparixin to weekly paclitaxel did not improve progression-free survival compared to paclitaxel alone, with median PFS of 5.5 months for the Reparixin group and 5.6 months for the placebo group.

Both treatment groups experienced similar rates of serious adverse events and grade ≥3 adverse reactions, indicating that the combination therapy was safe but did not provide the expected therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer (fRida). Goldstein, LJ., Mansutti, M., Levy, C., et al.[2022]

In a phase II trial involving 46 patients with RAS-mutant metastatic colorectal cancer, regorafenib showed a median overall survival of 18.9 months and a disease control rate of 54.6%, indicating its potential effectiveness in this patient population.

Although the study did not meet its primary endpoint of progression-free patients after 6 months, regorafenib was well tolerated with manageable side effects, and patients with favorable characteristics (like a single metastatic site) experienced better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib monotherapy as second-line treatment of patients with RAS-mutant advanced colorectal cancer (STREAM): an academic, multicenter, single-arm, two-stage, phase II study. Cardone, C., De Stefano, A., Rosati, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06541262

Study Details | NCT06541262 | Silmitasertib (CX-4945) in ... The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid ...

2. childrensmercy.org childrensmercy.org/childrens-mercy-research-institute/studies-and-trials/results/Details?id=d561d42733abea50d8b0d4e45d5c7b82

A study of Silmitasertib (CX-4945) for relapsed or refractory ... The goal of this study for both Phases I & II is to find what effects, good and/or bad, the drug silmitasertib has on children and young adults with relapsed or ...

3. nicklauschildrens.org nicklauschildrens.org/medical-services/research-institute-(clinical-trials)/clinical-trials/onc24057-(bcc021)

The Nicklaus Children's Research Institute The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs ...

4. cancer.gov cancer.gov/clinicaltrials/NCI-2024-09844

Silmitasertib (CX-4945) in Combination With ... The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid ...

5. ufhealth.org ufhealth.org/clinical-trials/bcc021ph-i-ii-silmitasertib-cx-4945w-chemo-in-children-and-young-adults-w-relapsed-refractory-st

BCC021:Ph I/II Silmitasertib (CX-4945)w/chemo in children ... The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid ...

6. careacross.com careacross.com/clinical-trials/trial/NCT06541262

Silmitasertib CX4945 in Combination With Chemotherapy ... Standard of care therapy for sarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy. 5. Measurable or ...

7. targetedonc.com targetedonc.com/view/fda-receives-ind-submission-for-phase-1-2-trial-of-silmitasertib-in-solid-tumors

FDA Receives IND Submission for Phase 1/2 Trial of ... The trial will be conducted in 2 phases with the first phase looking to determine the safety and dosage of silmitasertib when used for treating ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10041529/

Silmitasertib (CX-4945), a Clinically Used CK2-Kinase ... It was granted orphan drug designation by the FDA for cholangiocarcinoma (bile duct cancer) in 2017 and is developed as a drug candidate in ...