Recruiting
Phase 1
Phase 2

Trabectedin & Ipilimumab & Nivolumab

Sponsor:

Sarcoma Oncology Research Center, LLC

Code:

NCT03138161

Conditions

Advanced Soft Tissue Sarcoma

Metastatic Soft Tissue Sarcoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Trabectedin

Ipilimumab

Nivolumab

Study Details

Brief summary:

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.

Conditions

Advanced Soft Tissue Sarcoma

Metastatic Soft Tissue Sarcoma

Study ID

NCT03138161

Start date

Apr 13, 2017

Status verified date

Feb, 2025

Completion date

Jul 31, 2031

Anticipated

Primary completion date

Dec 31, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Individuals must meet all of the inclusion criteria in order to be eligible to participate in the study, as follows:

  • Male or Female ≥ 18 years of age
  • Pathologically confirmed diagnosis of locally advanced unresectable or metastatic soft tissue sarcoma
  • For the Phase 1 Part of Study, previously treated patients will be enrolled. For the Phase 2 Part of Study, previously treated patients will be enrolled.
  • Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the investigator's IRB/Ethics Committee
  • Willingness to comply with all study procedures and availability for the duration of the study.
  • Measurable disease by RECIST v1.1
  • ECOG performance status ≤1
  • Life expectancy of at least 3 months
  • Acceptable liver function: Bilirubin ≤ 1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level ≤ 3.0 ULN);AST (SGOT), ALT (SGPT) and alkaline phosphatase ≤ 3 x ULN (≤ 5 x ULN if liver metastases)
  • Acceptable renal function: Creatinine ≤1.5 times ULN or ≥ 60 mL/min (using the Cockcroft Gault formula)
  • 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
  • All women of childbearing potential must have a negative pregnancy test and all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose.

Exclusion Criteria:

  • All individuals meeting any of the exclusion criteria at baseline will be excluded from study participation, as follows:

  • Subjects with untreated CNS metastases. Subjects are eligible if CNS metastases have been adequately treated and have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to treatment initiation. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment initiation.
  • Subjects with carcinomatous meningitis
  • Anticancer treatment with radiation therapy, chemotherapy, targeted therapy or other antitumor treatment within 2 weeks prior to study entry
  • Subjects who participated in an investigational drug or device study within 14 days prior to study entry
  • Females who are pregnant or breast-feeding
  • Unwillingness or inability to comply with the study protocol for any reason
  • Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment
  • • History of or known or suspected autoimmune disease (exception(s): patients with vitiligo, Type I diabetes, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at Screening are allowed). Other exceptions may be allowed following discussion with the Sponsor Medical Monitor for patients who have not received treatment for their autoimmune disorder in the past 3 years.
  • Systemic immunosuppression, including HIV positive status with or without AIDS
  • Skin rash (psoriasis, eczema) affecting ≥ 25% body surface area
  • Inflammatory bowel disease (Crohn's or ulcerative colitis)
  • Ongoing or uncontrolled diarrhea within 4 weeks of trial enrollment
  • Recent history of acute diverticulitis, intraabdominal abscess or gastrointestinal obstruction within 6 months of trial enrollment, which are known risk factors for bowel perforation
  • Patients with congestive heart failure or recent cardiac event
  • Evidence of severe or uncontrolled systemic disease or any other concurrent condition, including psychiatric, which in the principal investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the trial
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Inadequate hematologic, renal or hepatic function defined by any of the following screening laboratory values: WBC ≤2000/µL; Neutrophils ≤1500/µL; Platelets ≤ 100,000/µL; hemoglobin ≤9.0 g/dL; Serum creatinine ≥1.5 x ULN or creatinine clearance ≤ 60 mL/min (using the Cockcroft Gault formula); AST/ALT ≥3 x ULN (≥ 5 x ULN if liver metastases); Total Bilirubin ≥1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level ≥ 3.0 ULN)
  • Current, active or previous history of heavy alcohol abuse
  • Pituitary endocrinopathy
  • Adrenal insufficiency or excess

Study Design

Enrollment

250 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1

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.

Interventions

Trabectedin

Trabectedinis an alkylating drug indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen.

Ipilimumab

Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for (1) treatment of unresectable or metastatic melanoma, and (2) adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.

Nivolumab

A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand (PD-L2), which is primarily expressed on APCs (antigen presenting cells). This results in the activation of T-cells and cell-medicated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.

Primary outcome measure

  • Maximum tolerated dose [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

Erlinda M Gordon, MD

310-552-9999egordon@sarcomaoncology.com

Victoria Chua-Alcala, MD

310-552-9999vchua@sarcomaoncology.com

Locations

Sarcoma Oncology Research Center

Recruiting

Santa Monica, California, United States, 90403

Contacts

Erlinda M Gordon, MD

310-552-9999egordon@sarcomaoncology.com

Victoria Chua-Alcala

310-552-9999vchua@sarcomaoncology.com

Principal Investigator:

Erlinda M Gordon, MD

More Information

Sponsor

Sarcoma Oncology Research Center, LLC

Last update posted

Feb 24, 2025

Last verified

Feb, 2025

Keywords

  • cancer immunotherapy, combination chemo-/immunotherapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Sarcoma Oncology Research Center, LLC on 2025-02-24.