SAINT:Trabectedin, Ipilimumab and Nivolumab for Previously Treated Advanced Soft Tissue Sarcoma

ConditionsAdvanced Soft Tissue Sarcoma Metastatic Soft Tissue Sarcoma

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorSarcoma Oncology Research Center, LLC

About 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

Trabectedin
Drug
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
Drug
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
Drug
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.

Treatment groups

250 Participants

are divided into 1 treatment group

Group A: Phase 1Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

Maximum tolerated dose

Dose escalation study, determination of maximum tolerated dose (MTD) in previoiusly treated patients with soft tissue sarcoma followed by expansion to previously untreated patients with advanced STS

Time frame

6 months

Secondary outcomes

Objective response rate (ORR), disease control rate (DCR)

Effect of triple therapy with trabectedin, ipilimumab and nivolumab on ORR and DCR in advanced soft tissue sarcoma

Time frame

24 months

Progression free survival (PFS), 6 month PFS rate

Effect of triple therapy with trabectedin, ipilimumab and nivolumab on progression free survival (PFS), 6 month PFS rate

Time frame

24 months

Overall survival (OS), 6 month OS rate

Effect of triple therapy with trabectedin, ipilimumab and nivolumab on overall survival in advanced soft tissue sarcoma

Time frame

24 months

Other outcomes

Tumor response and PD-1, PD-L1 expression in tumors

Correlation of response with PD-L1 expression and other biomarkers in patients' tumors

Time frame

30 months

Dexamethasone and immune related events

• Correlation of the timing and effect of dexamethasone use (necessarily given with TRABECTEDIN) on absolute lymphocyte count and the immune response, including immune related adverse events

Time frame

30 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sarcoma Oncology Research Center, LLC

Lead sponsor

Source ClinicalTrials.gov

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