metastatic or inoperable soft tissue sarcoma MedDRA version: 20.0 Level: PT Classification code 10024191 Term: Leiomyosarcoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10024194 Term: Leiomyosarcoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10024629 Term: Lipos
Conditions
Interventions
Trade Name: Opdivo®
Product Name: Nivolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NIVOLUMAB
CAS Number: 946414-94-4
Other descriptive name: NIVOLUMAB
Concentr
Sponsors
Universitätsmedizin Greifswald
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Group A: 1 Patients must have histologically confirmed liposarcoma or leiomyosarcoma • Group B: 1 Patients 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) 3 Signed Written Informed Consent 4 Men and women aged = 18 years. 5 Eastern Cooperative Oncology Group (ECOG) performance status = 1. 6 Measurable disease (according to RECIST criteria version 1.1) 7 Locally advanced/unresectable or metastatic disease 8 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 9 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 10 Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 4.0, grade 1 or less 11 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. 12 Absolute neutrophil count (ANC) = 1,500/mm3 13 Platelet count = 100,000/mm3 14 Creatine phosphokinase (CPK) =2,5 x ULN 15 Creatinine = 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance = 60 mL/min (calculated by using the Cockcroft-Gault formula) 16 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). 17 AST/ALT = 2.5 x upper limit of normal (ULN) 18 AP = 2.5 x upper limit of normal (ULN) 19 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. 20 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 21 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. 22 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 a
Exclusion criteria
Exclusion criteria: 1 Prior exposure to trabectedin 2 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. 3 Patients 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 5 Known significant chronic liver disease, such as cirrhosis or active hepatitis B or C o 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 (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 o Hepatitis C can be defined as: • Hepatitis C antibody (Ab) positive • Presence of hepatitis C virus (HCV) ribonucleic acid (RNA) 6 Known active pulmonary disease with hypoxia defined as: o Oxygen saturation 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration 8 Myocardial 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 9 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 10 Unwilling or unable to have a central venous catheter 11 Known allergies, hypersensitivity, or intolerance to trabectedin, dexamethasone, or their excipients, or monoclonal antibodies (biologics) therapy 12 Pregnant or breast-feeding 13 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 14 On-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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy endpoint of the trial is the progression-free survival rate after 6 months (PFSR6), assessed by applying RECIST 1.1. 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;Secondary Objective: Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), duration of disease stabilization (DoDS) and PDL-1-Expression. Safety parameters: · Discontinuation rate and dose reductions for Nivolumab plus trabectedin treatment · Treatment duration (number of cycles) · Delay of treatment · Reason for discontinuation of treatment · Assessment of adverse events according to CTCAE 4.0 ;Primary end point(s): The primary efficacy endpoint of the trial is the progression-free survival rate after 6 months (PFSR6), assessed by applying RECIST 1.1. 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 as determined by the nature and frequency of AEs according to CTCAE 4.0;Timepoint(s) of evaluation of this end point: Primary efficacy endpoint will be assessed 6 months after start of treament Primary safety endpoint: AEs / SAEs / Treatment Emergent Adverse Events according to CTCAE 4.0 will be analyzed at the end of study. An Interim safety analysis will be done after the treatment of 18 patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), duration of disease stabilization (DoDS) and PDL-1-Expression. Safety parameters: · Discontinuation rate and dose reductions for Nivolumab plus trabectedin treatment · Treatment duration (number of cycles) · Delay of treatment · Reason for discontinuation of treatment · Assessment of adverse events according to CTCAE 4.0 ;Timepoint(s) of evaluation of this end point: Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), duration of disease stabilization (DoDS) and PDL-1-Expression will be assessed at the end of study. Safety parameters: · Discontinuation rate and dose reductions for Nivolumab plus trabectedin treatment · Treatment duration (number of cycles) · Delay of treatment · Reason for discontinuation of treatment will be assessed at the end of study. · Adverse events according to CTCAE 4.0 will be analyzed after the end of study. | — |
Countries
Germany
Contacts
Public ContactProf. Dr. Salah-Eddin Al-Batran
Institut für Klinisch-Onkologische Forschung
Outcome results
None listed