Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Group A:

1 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.
Absolute neutrophil count (ANC) ≥ 1,500/mm3
Platelet count ≥ 100,000/mm3
Creatine phosphokinase (CPK) ≤2,5 x ULN
Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance ≥ 60 mL/min (calculated by using the Cockcroft-Gault formula)
Total bilirubin ≤ upper limit of normal (ULN). If total bilirubin is greater than (>) ULN, measure indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin is within normal range, participant may be eligible).
AST/ALT ≤ 2.5 x upper limit of normal (ULN)
AP ≤ 2.5 x upper limit of normal (ULN)
Hemoglobin ≥ 9 g/dl. If hemoglobin <9 g/dl, blood transfusion is permitted. If hemoglobin cannot be enhanced to ≥ 9 g/dl, patient cannot be included into the study.
Thyroid stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH if free T4 is normal and patient is clinically euthyroid, patient is eligible
Not pregnant and not nursing; for women of childbearing potential who are sexually active, a negative pregnancy test (urinary or serum beta-HCG) at screening (performed ≤7 days prior to registration) is required.
Female participants must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the investigator), or if sexually active, follow the contraceptive guidance in Appendix 4 throughout the duration of study treatment and for a minimum of 5 months after the last dose of study medication. Male participants must agree to use an adequate contraception method as deemed appropriate by the investigator (e.g., vasectomy, double-barrier, partner using effective contraception) and to not donate sperm for a minimum of 7 months after the last dose of study medication.

Exclusion Criteria:

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:

Hepatitis C antibody (Ab) positive
Presence of hepatitis C virus (HCV) ribonucleic acid (RNA)

Known active pulmonary disease with hypoxia defined as:

Oxygen saturation < 85% on room air or
Oxygen saturation < 88% despite supplemental oxygen
Systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration
Myocardial infarct within 6 months before enrollment, New York Heart Association Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection, or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures
Unwilling or unable to have a central venous catheter
Known allergies, hypersensitivity, or intolerance to trabectedin, dexamethasone, or their excipients, or monoclonal antibodies (biologics) therapy
Pregnant or breast-feeding
Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements
On-treatment participation in another clinical study in the period 30 days prior to start of study treatment and during the study.
History of allogeneic solid organ or tissue transplant including allogeneic hematopoetic stem cell transplantation.