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

NCT03138161 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SOC-1702
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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

Keywords

cancer immunotherapy, combination chemo-/immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (3)

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

  24 months

• Progression free survival (PFS), 6 month PFS rate

  24 months

• Overall survival (OS), 6 month OS rate

  24 months

Other Outcomes (2)

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

  30 months

• Dexamethasone and immune related events

  30 months

Study Arms (1)

Phase 1

EXPERIMENTAL

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.

Drug: Trabectedin; Drug: Ipilimumab; Drug: Nivolumab

Interventions

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.

Also known as: Yondelis

Phase 1

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.

Also known as: Yervoy

Phase 1

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.

Also known as: Opdivo

Phase 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarcoma Oncology Research Center, LLC: lead

Study Sites (1)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

RECRUITING

Related Publications (4)

• Gordon EM, Sankhala KK, Chawla N, Chawla SP. Trabectedin for Soft Tissue Sarcoma: Current Status and Future Perspectives. Adv Ther. 2016 Jul;33(7):1055-71. doi: 10.1007/s12325-016-0344-3. Epub 2016 May 27.

  PMID: 27234989 BACKGROUND

• Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. doi: 10.1200/JCO.2015.62.4734. Epub 2015 Sep 14.

  PMID: 26371143 BACKGROUND

• Hellman MD, Gettinger SN, Goldman JW, et al. CheckMate 012: Safety and efficacy of first-line (1L) NIVOLUMAB (nivo;N) and IPILIMUMAB (ipi;I) in advanced (adv) NSCLC. J Clin Oncol 2016, 34: (suppl; abstr 3001).

  BACKGROUND

• Gordon EM, Sankhala KK, Stumpf N, Tseng WW, Chawla SP. Cancer immunotherapy with sequential administration of trabectedin and nivolumab in advanced soft tissue sarcoma. Presented at the Society of Immunotherapy for Cancer/ ITOC, Prague, Czech Republic, March, 2017

  BACKGROUND

MeSH Terms

Conditions

Sarcoma

Interventions

Trabectedin; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Erlinda M Gordon, MD

  Sarcoma Oncology Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erlinda M Gordon, MD

CONTACT

310-552-9999; egordon@sarcomaoncology.com

Victoria Chua-Alcala, MD

CONTACT

310-552-9999; vchua@sarcomaoncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2017
• First Posted: May 3, 2017
• Study Start: April 13, 2017
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): July 31, 2031
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)