trabectedin plus olaparib in metastatic or advanced sarcomas (tomas)

Conditions: Soft Tissue Sarcoma; Bone Tumor

Summary: this is a phase 1b, multi-site, open-label, non-randomized clinical trial evaluating the safety, tolerability, and pharmacokinetics of escalating doses of olaparib and trabectedin in patients with unresectable advanced/metastatic sarcomas. patients will continue to be treated on this combination regimen in the absence of disease progression, intolerable toxicity or patient's decision.


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 \ 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

Keywords: trabectedin olaparib sarcoma bone tumor