Silmitasertib + Chemotherapy for Recurrent Solid Tumors

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

114 Participants Needed

Trial Summary

What is the purpose of this trial?

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 tumors. An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat. The goals of this part of the study are: * Establish a recommended dose of silmitasertib in combination with chemotherapy * Test the safety and tolerability of silmitasertib in combination with chemotherapy in subjects with cancer * To determine the activity of study treatments chosen based on: * How each subject responds to the study treatment * How long a subject lives without their disease returning/progressing

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.

What makes the drug Silmitasertib unique for treating recurrent solid tumors?

Silmitasertib is unique because it targets a specific enzyme called CK2, which is involved in cancer cell growth and survival, making it different from other treatments that may not target this enzyme. This approach could potentially offer a new way to treat recurrent solid tumors that have not responded to standard therapies. ^{1 2 3 4 5}

Research Team

Chandrika Behura, MD

Principal Investigator

Penn State Health Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England 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. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Regorafenib. [2018]

3. Netherlands 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). [2022]

4. England 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. [2023]

5. Germany 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. [2022]