Combined treatment with Nivolumab and Trabectedin in patients with metastatic or inoperable soft tissue Sarcomas
- Conditions
- metastatic or inoperable soft tissue sarcomaMedDRA version: 20.0Level: PTClassification code 10024191Term: Leiomyosarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10024194Term: Leiomyosarcoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10024629Term: Liposarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10024632Term: Liposarcoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10068595Term: Sarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001083-38-DE
- Lead Sponsor
- niversitätsmedizin Greifswald
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 92
•Group A:
1Patients must have histologically confirmed liposarcoma or leiomyosarcoma
•Group B:
1Patients must have histologically confirmed soft tissue sarcoma (STS) other than liposarcoma or leiomyosarcoma (excluding GIST)
•Both Groups (A and B):
2= 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy (anthracycline-containing regimen)
3Signed Written Informed Consent
4Men and women aged = 18 years.
5Eastern Cooperative Oncology Group (ECOG) performance status = 1.
6Measurable disease (according to RECIST criteria version 1.1)
7Locally advanced/unresectable or metastatic disease
8No 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
9No 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
10Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 4.0, grade 1 or less
11Patients 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.
12Absolute neutrophil count (ANC) = 1,500/mm3
13Platelet count = 100,000/mm3
14Creatine phosphokinase (CPK) =2,5 x ULN
15Creatinine = 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance = 60 mL/min (calculated by using the Cockcroft-Gault formula)
16Total 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).
17AST/ALT = 2.5 x upper limit of normal (ULN)
18AP = 2.5 x upper limit of normal (ULN)
19Hemoglobin = 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.
20Thyroid 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
21Not 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.
22Female 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 a
1Prior exposure to trabectedin
2Active 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.
3Patients with human immunodeficiency virus (HIV) infection are excluded unless cluster of differentiation (CD)4+ cells are > 350 and no viral load is detectable
4 Symptomatic, untreated, or uncontrolled brain metastases present
5Known significant chronic liver disease, such as cirrhosis or active hepatitis B or C
oHepatitis 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 (10exp4 copies/ml)
•Persistent or intermittent elevation in alanine aminotransferase (ALT)/alanine aminotransferase (AST) levels
•Liver biopsy showing chronic hepatitis with moderate or severe necroinflammation
oHepatitis C can be defined as:
•Hepatitis C antibody (Ab) positive
•Presence of hepatitis C virus (HCV) ribonucleic acid (RNA)
6Known active pulmonary disease with hypoxia defined as:
oOxygen saturation < 85% on room air or
oOxygen saturation < 88% despite supplementaloxygen
7Systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration
8Myocardial infarct within 6 months before enrollment, New York Heart Association Class III 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
9Uncontrolled 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
10Unwilling or unable to have a central venous catheter
11Known allergies, hypersensitivity, or intolerance to trabectedin, dexamethasone, or their excipients, or monoclonal antibodies (biologics) therapy
12Pregnant or breast-feeding
13Any 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
14On-treatment participation in another clinical study in the period 30 days prior to start of study treatment and during the study
15 History of allogeneic solid organ or tissue transplant including allogeneic hematopoetic stem cell transplantation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method