Trabectedin + Immunotherapy for Soft Tissue Sarcoma

Recruiting in Palo Alto (17 mi)

Overseen by Erlinda M Gordon, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Sarcoma Oncology Research Center, LLC

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, HIV, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is an open label, dose-seeking phase 1/2 study using escalating doses of TRABECTEDIN given intravenously with defined doses of IPILIMUMAB and NIVOLUMAB based on preliminary results of the Checkmate 012 trial for NSCLC (Hellman et al., 2016). For the Phase 1 Part of Study, only previously treated patients will be enrolled. For the Phase 2 Part of Study, previously treated patients will be enrolled.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had anticancer treatments like chemotherapy or radiation within 2 weeks before joining the study.

What data supports the effectiveness of the drugs Trabectedin, Ipilimumab, Yervoy, Nivolumab, and Opdivo for treating soft tissue sarcoma?

Research shows that the combination of nivolumab and ipilimumab has been effective in prolonging overall survival in patients with advanced non-small cell lung cancer (NSCLC) and melanoma, suggesting potential benefits in other cancers. Additionally, ipilimumab has shown significant overall survival benefits in melanoma, and nivolumab is favored for its favorable toxicity profile. ^{1 2 3 4 5}

Is the combination of Trabectedin and Immunotherapy safe for humans?

The combination of nivolumab and ipilimumab, which are types of immunotherapy, has been studied in cancer patients and shown to increase the risk of side effects like colitis (inflammation of the colon), pneumonitis (lung inflammation), and diarrhea compared to using nivolumab alone. Ipilimumab can also cause skin-related side effects like rashes and itching, but these are usually manageable with proper care. ^{6 7 8 9 10}

How is the drug combination of Trabectedin, Ipilimumab, and Nivolumab unique for treating soft tissue sarcoma?

This drug combination is unique because Trabectedin, which is effective in controlling tumors resistant to other treatments, is being combined with immunotherapy drugs Ipilimumab and Nivolumab to potentially enhance the immune system's ability to fight the cancer. Trabectedin also has a favorable safety profile compared to traditional chemotherapy drugs, making it a promising option for long-term tumor control with better quality of life. ^{11 12 13 14 15}

Research Team

Erlinda M Gordon, MD

Principal Investigator

Sarcoma Oncology Research Center

Eligibility Criteria

Adults over 18 with advanced soft tissue sarcoma, either previously treated (Phase 1) or untreated (Phase 2), who understand the study and consent to participate. They must have acceptable organ function, no severe skin conditions, heart failure, bowel diseases, recent serious infections or immunosuppression. Women of childbearing age need a negative pregnancy test and all participants must agree to use effective contraception.

Inclusion Criteria

My kidney function, measured by creatinine levels, is within the normal range.

Acceptable hematologic status (without hematologic support): WBC ≥2000/µL; ANC ≥ 1500 cells/μL; Platelet count ≥ 100,000/μL; Hemoglobin ≥ 9.0 g/dL; Normal PT, PTT, INR

I am not pregnant and agree to use effective birth control during and after the study.

Exclusion Criteria

I have previously been treated with specific immunotherapy drugs.

I am not pregnant or breastfeeding.

I have received immunotherapy targeting CTLA4 or PD-1.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Phase 1

Patients receive escalating doses of Trabectedin with Ipilimumab and Nivolumab to determine the maximum tolerated dose

Up to 54 weeks

Every 3 weeks for Trabectedin, every 12 weeks for Ipilimumab, every 2 weeks for Nivolumab

Expansion Phase 2

Patients receive the maximum tolerated dose of Trabectedin with Ipilimumab and Nivolumab to assess safety and efficacy

Up to 54 weeks

Every 3 weeks for Trabectedin, every 12 weeks for Ipilimumab, every 2 weeks for Nivolumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Ipilimumab (Checkpoint Inhibitor)
• Nivolumab (Monoclonal Antibodies)
• Trabectedin (Alkylating agents)

Trial Overview The trial is testing combinations of Trabectedin with Ipilimumab and Nivolumab in escalating doses for first-line treatment of advanced soft tissue sarcoma. It's an open-label study where everyone knows what treatment they're getting; Phase 1 seeks safe dosages while Phase 2 tests effectiveness in untreated patients.

Participant Groups

Group I: Phase 1 Experimental Treatment 3 Interventions

Phase 1: 3-6 will be treated with escalating doses of Trabectedin every 3 weeks up to 18 doses. Dose Level 1 is 1.0 mg/m2; Dose Level 2,1.2 mg/m2; Dose Level 3,1.5 mg/m2. Beginning 2 weeks after the first dose of Trabectedin, all patients will be treated with Ipilimumab at 1 mg/kg every 12 weeks up to 5 doses, and Nivolumab at 3 mg/kg every 2 weeks up to 26 doses. Phase 2: All patients will be treated with the maximum tolerated dose of Trabectedin every 3 weeks. Beginning 2 weeks after the first dose of Trabectedin, all patients will be treated with Ipilimumab at 1 mg/kg every 12 weeks up to 5 doses, and Nivolumab at 3 mg/kg every 2 weeks up to 26 doses.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Sarcoma Oncology Research Center Santa Monica, CA

Who Is Running the Clinical Trial?

Sarcoma Oncology Research Center, LLC

Lead Sponsor

Trials

9

Patients Recruited

910+

Bristol-Myers Squibb

Industry Sponsor

Trials

2731

Patients Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Findings from Research

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

In the phase III CheckMate 238 trial, 67.7% of patients receiving nivolumab experienced treatment-related adverse events (TRAEs), with the most common being pruritus and diarrhea, primarily occurring within the first 3 months of treatment.

Despite the high incidence of TRAEs, there was no significant association found between these adverse events and recurrence-free survival (RFS), indicating that the safety profile of nivolumab remains consistent and does not negatively impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. Mandala, M., Larkin, J., Ascierto, PA., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of dabrafenib in combination with trametinib versus competing adjuvant therapies for high-risk melanoma. [2020]

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

Targeted Therapy Given after Anti-PD-1 Leads to Prolonged Responses in Mouse Melanoma Models through Sustained Antitumor Immunity. [2022]

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

First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. [2022]

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

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

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

Adjuvant Therapy of Melanoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. [2022]

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

Ipilimumab in patients with cancer and the management of dermatologic adverse events. [2017]

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

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Clinical experience with ipilimumab 10 mg/kg in patients with melanoma treated at Italian centres as part of a European expanded access programme. [2023]

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

Trabectedin: novel insights in the treatment of advanced sarcoma. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Trabectedin (ET-743): evaluation of its use in advanced soft-tissue sarcoma. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Immunologic Gene Signature Analysis Correlates Myeloid Cells and M2 Macrophages with Time to Trabectedin Failure in Sarcoma Patients. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Current questions in soft tissue sarcoma: further steps with Yondelis®. [2018]

15. England pubmed.ncbi.nlm.nih.gov

13 years of trabectedin, 5 years of Yondelis®: what have we learnt? [2018]