CDK4/6 Inhibitor for Liposarcoma

Recruiting at 9 trial locations

Overseen By Dinah M Jaunakais, M.Ed.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Shanghai Pharma Biotherapeutics USA Inc.

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: CDK4 negative, CNS metastases, 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

Compensation: Varies

Number of Visits: 19

Duration: 36 weeks

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests SPH4336, a chemotherapy pill, in patients with CDK4-positive liposarcomas. The drug works by blocking an enzyme that cancer cells need to grow, aiming to stop tumor growth.

Will I have to stop taking my current medications?

The trial requires that you do not take strong CYP3A4 inhibitors or inducers at the start of the study. If you are on such medications, you may need to stop them before participating.

What data supports the effectiveness of the drug SPH4336 for treating liposarcoma?

Research shows that drugs similar to SPH4336, which inhibit CDK4/6, have been effective in reducing tumor growth in liposarcoma by targeting the CDK4 gene, which is often amplified in these tumors. Studies with other CDK4/6 inhibitors like LEE011 and palbociclib have shown promising results in slowing down or stopping the growth of liposarcoma cells. ^{1 2 3 4 5}

Is the CDK4/6 inhibitor safe for humans?

In studies with CDK4/6 inhibitors like LEE011 and palbociclib, treatment in mice and humans showed tumor growth reduction without harmful effects on mouse weight, but moderate blood-related side effects were noted in humans. ^{1 2 3 5 6}

How is the drug SPH4336 different from other treatments for liposarcoma?

SPH4336 is a CDK4/6 inhibitor, which targets the CDK4 gene that is highly amplified in most well-differentiated and dedifferentiated liposarcomas, making it a promising option compared to conventional chemotherapy that has limited effectiveness for this condition. ^{1 2 3 4 5}

Research Team

Kenneth W Locke, PhD

Principal Investigator

Shanghai Pharma Biotherapeutics USA Inc.

Eligibility Criteria

Adults over 18 with advanced liposarcomas, either dedifferentiated or well-differentiated/dedifferentiated, who have had no more than three prior treatments and show tumor progression. Participants must be in good physical condition (ECOG 0 or 1), not have major organ dysfunction, agree to use effective contraception, and provide tissue samples for research.

Inclusion Criteria

My sarcoma is confirmed and has spread or is advanced.

I am fully active or can carry out light work.

I have had 3 or fewer previous cancer treatments.

Exclusion Criteria

I have been treated with a CDK4/6 inhibitor before.

I currently have COVID-19.

Any other medical or psychiatric condition, or laboratory abnormality that would result in an unacceptable risk with study participation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Initial 10 subjects are evaluated for safety after completing at least 1 cycle

4 weeks

1 visit (in-person)

Treatment

Participants receive SPH4336 orally once daily in 28-day cycles

36 weeks

Visits every 6 weeks for tumor assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Visits every 12 weeks

Treatment Details

Interventions

• SPH4336

Trial Overview The trial is testing SPH4336, a selective enzyme blocker designed to treat specific types of liposarcomas. It's an open-label study meaning everyone gets the drug; there's no placebo group. The focus is on safety, how the body processes the drug (pharmacokinetics), and its initial effectiveness against tumors.

Participant Groups

Group I: SPH4336 Experimental Treatment 1 Intervention

400 mg (2 - 200 mg tablets) PO QD

Who Is Running the Clinical Trial?

Shanghai Pharma Biotherapeutics USA Inc.

Lead Sponsor

Trials

2

Recruited

40+

Findings from Research

In a phase 2 clinical trial involving 60 patients with advanced well-differentiated or dedifferentiated liposarcomas (WD/DDLS), palbociclib at a new dose of 125 mg daily for 21 days every 28 days resulted in a progression-free survival (PFS) rate of 57.2% at 12 weeks, indicating its efficacy in this patient population.

The treatment was associated with manageable hematologic toxic effects, primarily neutropenia, suggesting that this dosing schedule may be safer compared to the previously tested regimen of 200 mg for 14 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial. Dickson, MA., Schwartz, GK., Keohan, ML., et al.[2022]

A genomic analysis of 56 liposarcoma samples revealed that while there were few gene mutations, over half of the samples exhibited gene amplifications, particularly of MDM2, CDK4, and receptor tyrosine kinases (RTKs).

In laboratory tests, combining CDK4 and IGF1R inhibitors effectively suppressed the growth of a well-differentiated liposarcoma cell line with IGF1R amplification, suggesting that this combination therapy could be a promising treatment for patients with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. Asano, N., Yoshida, A., Mitani, S., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Antiproliferative effects of CDK4/6 inhibition in CDK4-amplified human liposarcoma in vitro and in vivo. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting CDK4 (cyclin-dependent kinase) amplification in liposarcoma: A comprehensive review. [2020]

6. Ireland pubmed.ncbi.nlm.nih.gov

Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells. [2021]