Clinical trial NCT02398058 (phase 1, status: unknown status)
Conditions: soft tissue sarcoma, bone tumor
ICD codes: C46.1
Drugs: trabectedin, olaparib
SMILES: [H][C@@]12[C@@H]3SC[C@]4(NCCC5=C4C=C(OC)C(O)=C5)C(=O)OC[C@H](N1[C@@H](O)[C@@H]1CC4=CC(C)=C(OC)C(O)=C4[C@H]2N1C)C1=C2OCOC2=C(C)C(OC(C)=O)=C31, OC1=NN=C(CC2=CC(C(=O)N3CCN(CC3)C(=O)C3CC3)=C(F)C=C2)C2=CC=CC=C12
Eligibility criteria:

        Inclusion Criteria:

          -  written informed consent

          -  histologically documented and not surgically resectable or metastatic sarcomas which
             progressed after first or further line treatments for relapsing disease

          -  Measurable disease as defined by RECIST v1.1.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0/1. ECOG PS 2 are
             eligible if depends solely on orthopedic problems

          -  Estimated life expectancy of ≥ 4 months

          -  Age ≥18 years

          -  Adequate organ function: Hemoglobin > 10.0 g/dl; Absolute neutrophil count (ANC)
             >1,500/mm3; Platelet count >= 100,000/μl; Total bilirubin < 1.5 times the upper limit
             of normal (ULN); ALT and AST < 2.5 x ULN (< 5 x ULN for patients with liver
             involvement of their cancer); Alkaline phosphatase < 2.5 x ULN; PT-INR/PTT < 1.5 x
             ULN; Serum creatinine < 1.5 x ULN or creatinine clearance ≥ 50 ml/min; Albumin > 25
             g/l; Creatine phosphokinase (CPK) < 2.5 x ULN

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study

          -  Previous enrolment in the present study

          -  Participation in another clinical study with an investigational product during the
             last month

          -  Persistent toxicities (≥CTCAE grade 2) with the exception of alopecia, caused by
             previous anticancer therapies

          -  Dementia or significantly altered mental status

          -  Patients with any severe and/or uncontrolled medical conditions

          -  HIV infection

          -  Active clinically serious infections (> grade 2 NCI-CTCAE version 4.03).

          -  Active viral hepatitis (HBV or HCV infection)

          -  Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months
             from definitive therapy, does not require corticosteroid treatment, has a negative
             imaging study within 4 weeks of study entry and is clinically stable with respect to
             the tumor at the time of study entry).

          -  Patients with seizure disorders requiring medication (such as steroids or
             anti-epileptics)

          -  Pregnant or breast-feeding patients. Women of childbearing potential must have a
             negative pregnancy test performed within 7 days before the start of treatment. Both
             men and women enrolled in this trial must use adequate barrier birth control measures
             during the course of the trial and 5 months after last dose of study drug

          -  Patients with evidence or history of bleeding diathesis

          -  Patients undergoing renal dialysis

          -  Patients unable to swallow oral medications

          -  Uncontrolled diabetes (fasting glucose > 2 x ULN)

          -  Patients receiving chronic, systemic treatment with corticosteroids or another
             immunosuppressive agent (except corticosteroids with a daily dosage equivalent to
             prednisone ≤ 20 mg for adrenal insufficiency). Topical or inhaled corticosteroids are
             permitted

          -  Patients with a history of another malignancy within 5 years prior to study entry,
             except curatively treated non-melanotic skin cancer or in-situ cervical cancer or
             other solid tumors curatively treated with no evidence of disease for ≥5 years.

          -  Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of
             treatment start

          -  Radiotherapy during study or within 3 weeks of start of study drug. (Palliative
             radiotherapy allowed)

          -  Major surgery within 4 weeks of start of study

          -  Prior exposure to the study drugs or their analogues

          -  Patients with known hypersensitivity to trabectedin, olaparib or to their excipients

          -  Patients can receive a stable dose of bisphosphonates for bone metastases before and
             during the study as long as these were started at least 4 weeks prior to treatment
             with the study drugs

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the patient's participation in the study or evaluation of the study results

          -  A history of noncompliance to medical regimens or inability or unwillingness to return
             for scheduled visits

          -  Corrected QT interval on the 12-lead ECG (QTc) >470 msec (Bazett Formula)

          -  use of strong CYP3A4 inhibitors/inducers

          -  Patients with myelodysplastic syndrome/acute myeloid leukemia