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

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ClinicalTrials.gov Identifier: NCT03127215
Recruitment Status : Recruiting
First Posted : April 25, 2017
Last Update Posted : November 7, 2018
Sponsor:
Collaborators:
AstraZeneca
PharmaMar
Information provided by (Responsible Party):
National Center for Tumor Diseases, Heidelberg

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.

Condition or disease Intervention/treatment Phase
Cancers With DNA Repair-Deficiency Drug: Olaparib Drug: Physician's choice Drug: Trabectedin Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized
Masking: None (Open Label)
Masking Description: open label
Primary Purpose: Treatment
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
Actual Study Start Date : October 25, 2018
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm E: Olaparib / Trabectedin
Olaparib / Trabectedin
Drug: Olaparib
Olaparib 150 mg tablet

Drug: Trabectedin
Trabectedin 1.1mg/m² infusional solution

Arm C: Physician's choice
Physician's choice
Drug: Physician's choice
treatment according to current guidelines




Primary Outcome Measures :
  1. Disease Control Rate [ Time Frame: At week 16 (after 5 cycles of study medication) ]
    Randomized, open-label, multicenter phase-II study comparing olaparib in combination with trabectedin versus physician's choice. Primary efficacy endpoint is the disease control rate after 5 cycles.

  2. Tumor response rate [ Time Frame: At week 16 (after 5 cycles of study medication) ]
    Defined as the sum of complete remission (CR) and partial remission (PR) according to RECIST version 1.1 after 5 cycles of study medication


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Time from first administration of the IMP to time death from any cause until end of study (2.5 years) ]
    defined as the time from first administration of the IMP to time of death from any cause

  2. Incidence of Treatment-Emergent Adverse Events (toxicity, tolerability) [ Time Frame: Time from first administration of the IMP to subjects end of trial (approximately month 6) ]
    This endpoint includes all AEs, their severity, SAEs, the relation of AEs to the study treatment, dose modifications for toxicity and discontinuation of study treatment during the trial phase. Toxic effects will be graded according to the National Cancer Institute Common Toxicity Criteria

  3. Quality of life [ Time Frame: Before the first (week 0), at the third (week 8), and after the fifth treatment cycle (week 16) ]
    QoL will be assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases and demographics



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Written informed consent
  • Diagnosis of locally advanced or metastatic malignancy
  • Prior administration of standard treatment for primary and relapsed malignancy
  • Eastern Cooperative Oncology Group Performance Status ≤1
  • 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

Main Exclusion Criteria:

  • Hematological malignancies and primary brain tumors.
  • Concurrent treatment in another interventional clinical trial
  • Prior treatment with PARP inhibitors
  • Persistent toxicity (≥Grade 2 according to CTCAE 4.03)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03127215


Contacts
Contact: Richard Schlenk, MD +49622156 ext 6228 studienzentrale@nct-heidelberg.de

Locations
Germany
National Center for Tumordiseases (NCT) Recruiting
Heidelberg, Germany, 69120
Contact: R. Schlenk, MD    +49622156 ext 6228    studienzentrale@nct-heidelberg.de   
Sponsors and Collaborators
National Center for Tumor Diseases, Heidelberg
AstraZeneca
PharmaMar
Investigators
Principal Investigator: Stefan Froehling, MD NCT / DKFZ Heidelberg

Responsible Party: National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier: NCT03127215     History of Changes
Other Study ID Numbers: NCT-2017-0417
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
DNA Repair-Deficiency Disorders
Metabolic Diseases
Olaparib
Trabectedin
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents