Study of Olaparib/Trabectedin vs. Doctor's Choice in Solid Tumors (NCT-PMO-1603)

National Center for Tumor Diseases, Heidelberg

Status and phase: Completed; Phase 2

Conditions: Cancers With DNA Repair-Deficiency

Treatments: Drug: Physician's choice; Drug: Trabectedin; Drug: Olaparib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03127215

NCT-2017-0417

Details and patient eligibility

About

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.

Enrollment: 102 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

Arm E: Olaparib / Trabectedin

Experimental group

Description:

Olaparib / Trabectedin

Treatment:

Drug: Olaparib

Drug: Trabectedin

Arm C: Physician's choice

Other group

Description:

Physician's choice

Treatment:

Drug: Physician's choice