Clinical trial NCT03127215: Study of Olaparib/Trabectedin vs. Doctor's Choice in Solid Tumors
Official title: A Randomized Phase-2 Study of Trabectedin/Olaparib Compared to Physician's Choice in Subjects With Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancers With DNA Repair-Deficiency
Lead sponsor: National Center for Tumor Diseases, Heidelberg
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: PharmaMar
name: German Cancer Research Center
First posted: 2017-04-25
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized
Primary purpose: TREATMENT

Brief summary: Evaluation of the efficacy of the combination of olaparib and trabectedin in adult patients with locally advanced/metastatic solid tumors that failed standard treatment and whose molecular sequencing tumor profiles show homologous recombination repair (HRR) defects. The primary objective is to show superior disease control rate in patients with HRR-deficient tumors treated with olaparib and trabectedin compared to treatment according to current guidelines (physician's choice). This trial aims to establish whether the PARP-dependency of HRR-deficient tumors across entities can be exploited for therapeutic benefit.


Eligibility criteria: Main Inclusion Criteria:

* Written informed consent
* Progressive locally advanced or metastatic malignancy
* Prior administration of standard treatment for primary and relapsed malignancy
* Eastern Cooperative Oncology Group Performance Status ≤1
* Patients with central venous access device in place (central venous catheter or porta-cath)
* Age ≥18 and ≤70 years
* Identification of defective DNA repair via HR
* Adequate bone marrow, renal, and hepatic function
* Hemoglobin ≥10 g/dl
* Neutrophil count ≥1,500/mm3
* Platelet count ≥100,000/µl
* Bilirubin ≤1.5 x upper limit of normal (ULN)
* ALT and AST ≤2.5 x ULN (≤5 x ULN in patients with hepatic tumor involvement)
* Alkaline phosphatase ≤2.5 x ULN
* PT-INR/PTT ≤1.5 x ULN
* Albumin ≥25 g/l
* Creatine kinase ≤2.5 x ULN
* Serum creatinine 1.5 mg/dl or creatinine clearance 51 ml/min

Main Exclusion Criteria:

* Hematological malignancies and primary brain tumors.
* Concurrent treatment in another interventional clinical trial
* Prior treatment with PARP Inhibitors
* Patients with platinum-refractory disease, defined as progressive disease during or immediately after treatment with platinum based chemotherapy
* Persistent toxicity (\> Grade 2 according to CTCAE 5.0)
* Dementia or significant impairment of cognitive state
* History of HIV infection
* Clinical signs of active infection (\>Grade 2 according to CTCAE 4.03)
* History of viral hepatitis (HBV or HCV)
* Epilepsy requiring pharmacologic treatment
* Pregnancy
* Major surgical intervention 4 weeks prior to study inclusion
* Known hypersensitivity to any of the study drugs
* Hematologic malignancy
* QTc time prolongation \>500 ms or history of familial long-QT-syndrome
* Heart failure NYHA III/IV
* Severe obstructive or restrictive ventilation disorder
* Concomitant use of known strong CYP3A Inhibitors
* Concomitant use of known strong CYP3A inducers

Primary outcomes:
measure: Disease Control Rate
timeFrame: At week 16 (after 5 cycles of study medication)
Secondary outcomes:
measure: Overall survival
timeFrame: Time from first administration of the IMP to time death from any cause until end of study (2.5 years)
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Time from first administration of the IMP to subjects end of trial (approximately month 6)
measure: Patient reported outcomes
timeFrame: Before the first (week 0), at the third (week 8), and after the fifth treatment cycle (week 16)
measure: Tumor response rate
timeFrame: At week 16 (after 5 cycles of study medication)
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Medizinische Fakultät der TU Dresden
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Heidelberg
country: Germany
facility: National Center for Tumordiseases (NCT)
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes-Gutenberg-Universität Mainz
city: München
country: Germany
facility: Klinikum der Universität München-Großhadern
city: Stuttgart
country: Germany
facility: Klinik Schillerhöhe
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen
Study officials:
affiliation: NCT / DKFZ Heidelberg
name: Stefan Froehling, MD
role: PRINCIPAL_INVESTIGATOR
References: