Combined Treatment With Nivolumab and Trabectedin in Patients With Metastatic or Inoperable Soft Tissue Sarcomas

NCT03590210 | Completed Phase 2 DMC

• 2 other identifiers: GISG-152017-001083-38
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 9

Brief Summary

The "NiTraSarc" trial evaluates the efficacy and feasibility (as determined by the safety and tolerability) of combined treatment with trabectedin and nivolumab in patients with metastatic or inoperable soft tissue sarcomas

Conditions

Metastatic Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• progression free survival rate at 6 months - PFSR6

  The primary efficacy endpoint of the trial is the progression-free survival rate after 6 months (PFSR6), assessed by applying RECIST 1.1.

  after 6 months of treatment

• safety, as measured by: - Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, and deaths - Incidence of clinical laboratory test abnormalities

  The primary safety endpoint is to assess the feasibility of combined treatment with trabectedin and nivolumab in patients with metastatic or inoperable soft tissue sarcomas as determined by the safety and tolerability of the combination treatment.

  through study completion, an average of 24 months

Secondary Outcomes (5)

• overall response rate (ORR)

  through study completion, an average of 24 months

• overall survival (OS)

  through study completion, an average of 24 months

• progression-free survival (PFS)

  through study completion, an average of 24 months

• duration of disease stabilization (DoDS)

  through study completion, an average of 24 months

• PDL-1 expression

  through study completion, an average of 24 months

Study Arms (2)

Group A - L-sarcoma

EXPERIMENTAL

Patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen will receive drug treatment with trabectedin (1 cycle mono-therapy) followed by trabectedin/nivolumab combination (up to 15 additional cycles); 16 cycles in total

Drug: Trabectedin; Drug: Nivolumab

Group B - non-L-sarcoma

EXPERIMENTAL

Patients with unresectable or metastatic soft tissue sarcoma other than liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen (GIST excluded) will receive drug treatment with trabectedin (1 cycle mono-therapy) followed by trabectedin/nivolumab combination (up to 15 additional cycles); 16 cycles in total

Drug: Trabectedin; Drug: Nivolumab

Interventions

Trabectedin DRUG

Cycle 1 to 16 1.5mg/m² IV over 24 hours, q3w

Also known as: Yondelis

Group A - L-sarcoma; Group B - non-L-sarcoma

Nivolumab DRUG

Cycle 2 to 16 240 mg IV over 30 minutes, q3w

Also known as: Opdivo

Group A - L-sarcoma; Group B - non-L-sarcoma

Eligibility Criteria

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

You may qualify if:

• Group A:
• Patients must have histologically confirmed liposarcoma or leiomyosarcoma
• Group B:
• Patients must have histologically confirmed soft tissue sarcoma (STS) other than liposarcoma or leiomyosarcoma (GIST excluded)
• Both Groups (A and B):
• ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy (anthracycline-containing regimen)
• Signed Written Informed Consent
• Men and women aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Measurable disease (according to RECIST criteria version 1.1)
• Locally advanced/unresectable or metastatic disease
• No prior therapy with ipilimumab or nivolumab, or any agent targeting programmed cell death 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
• No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation ≤ 28 days before study registration; no treatment with nitrosourea or mitomycin ≤ 42 days before study registration
• Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 4.0, grade 1 or less
• Patients must have a formalin-fixed, paraffin-embedded (FFPE) tumor block OR 1 representative hematoxylin and eosin (H\&E) and 20 unstained sarcoma tissue slides available for submission to central pathology review. If no archival tissue is available, a fresh biopsy has to be performed during screening.

You may not qualify if:

• Prior exposure to trabectedin
• Active known or suspected autoimmune disease (e.g. autoimmune colitis, autoimmune panhypopituitarism, autoimmune adrenal insufficiency)
• EXCEPT:
• i) Subjects with vitiligo, type 1 diabetes mellitus, resolved childhood asthma or atopy are permitted to enroll.
• ii) Subjects with suspected autoimmune thyroid disorders may be enrolled if they are currently euthyroid or with residual hypothyroidism requiring only hormone replacement.
• iii) Subjects with psoriasis requiring systemic therapy must be excluded from enrollment.
• Patients with human immunodeficiency virus (HIV) infection are excluded unless cluster of differentiation (CD)4+ cells are \> 350 and no viral load is detectable
• Symptomatic, untreated, or uncontrolled brain metastases present
• Known significant chronic liver disease, such as cirrhosis or active hepatitis B or C
• Hepatitis B can be defined as (all of the following conditions must be met):
• Hepatitis B surface antigen (HBsAg) \> 6 months
• Serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥2,000 IU/ml (104 copies/ml)
• Persistent or intermittent elevation in alanine aminotransferase (ALT)/alanine aminotransferase (AST) levels
• Liver biopsy showing chronic hepatitis with moderate or severe necroinflammation
• Hepatitis C can be defined as:

Sponsors & Collaborators

• University Medicine Greifswald: lead
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: collaborator
• PharmaMar: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (9)

Helios Klinikum Bad Saarow, Klinik für Hämatologie, Onkologie und Palliativmedizin, Sarkomzentrum Berlin-Brandenburg

Bad Saarow, 15526, Germany

Location

Helios Klinikum Berlin Buch, Klinik für interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg

Berlin, 13125, Germany

Location

Charité Universitätsmedizin Berlin, Campus Virchow Klinikum Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie (CC14)

Berlin, 13353, Germany

Location

Medizinische Fakultät "Carl Gustav Carus" der TU Dresden, Medizinische Klinik I

Dresden, 01307, Germany

Location

Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie

Greifswald, 17475, Germany

Location

Universitätsklinikum Medizinische Fakultät Mannheim der Universität Heidelberg, Interdisziplinäres Tumorzentrum Mannheim (ITM)

Mannheim, 68167, Germany

Location

Universitätsklinikum Münster, Medizinische Klinik A Hämatologie / Onkologie / Pneumologie

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen, Innere Medizin II - Medizinische Onkologie und Pneumologie

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Hämatologie / Onkologie

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Trabectedin; 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

• Daniel Pink, MD

  Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie, Transplantationszentrum, Universitätsmedizin Greifswald

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two group, non-randomized

Study Record Dates

• First Submitted: June 21, 2018
• First Posted: July 18, 2018
• Study Start: June 8, 2018
• Primary Completion: February 12, 2022
• Study Completion: February 12, 2022
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)