Cancers With DNA Repair-DeficiencyPhase 2NCT-PMO-1603NCT03127215
Study of Olaparib/Trabectedin vs. Doctor's Choice in Solid Tumors
A Phase 2 study testing Olaparib, Physician's choice and Trabectedin in people with Cancers With DNA Repair-Deficiency, run by National Center for Tumor Diseases, Heidelberg at 9 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cancers With DNA Repair-Deficiency
- What is being tested?
- Olaparib, Physician's choice and Trabectedin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 9 sitesGermany
- Study dates
- 25 Oct 2018to 19 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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 locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Medizinische Fakultät der TU Dresden
Dresden, 01307
Universitätsklinikum Essen
Essen, 45147
Universitätsklinikum Frankfurt
Frankfurt, 60590
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
National Center for Tumordiseases (NCT)
Heidelberg, 69120
Universitätsmedizin der Johannes-Gutenberg-Universität Mainz
Mainz, 55131
Klinikum der Universität München-Großhadern
München, 81377
Klinik Schillerhöhe
Stuttgart, 70376
Universitätsklinikum Tübingen
Tübingen, 72076
About this study
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
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.
- Conditions
- Cancers With DNA Repair-Deficiency
- Being tested
- Olaparib, Physician's choice, Trabectedin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Olaparib 150 mg tablet
Physician's choiceDrug
treatment according to current guidelines
TrabectedinDrug
Trabectedin 1.1mg/m² infusional solution
| Study group | Role | What they receive |
|---|---|---|
| Arm E: Olaparib / Trabectedin | Experimental | Olaparib / Trabectedin Receives: Drug: Olaparib; Drug: Trabectedin |
| Arm C: Physician's choice | Other | Physician's choice Receives: Drug: Physician's choice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Control Rate
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.
Measured: At week 16 (after 5 cycles of study medication)
Secondary outcomes (4)
Overall survival
defined as the time from first administration of the IMP to time of death from any cause
Measured: Time from first administration of the IMP to time death from any cause until end of study (2.5 years)
Incidence of Treatment-Emergent Adverse Events
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.
Measured: Time from first administration of the IMP to subjects end of trial (approximately month 6)
Patient reported outcomes
Patient reported outcomes (PROs) including health-related quality of life (QoL) are calculated as the new European Organization for Research and Treatment of Cancer (EORTC). QLQ-C30 summary score recommended by teh EORTC Quality of Life Group. In addition, the EORTC QLQ function and symptom scores are calculated according to the actual EORTC Scoring Manual.
Measured: Before the first (week 0), at the third (week 8), and after the fifth treatment cycle (week 16)
Tumor response rate
Defined as the sum of complete remission (CR) and partial remission (PR) according to RECIST version 1.1 after 5 cycles of study medication
Measured: At week 16 (after 5 cycles of study medication)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2017
- Study start25 Oct 2018
- Primary completion19 Dec 2023
- Study completion19 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancers With DNA Repair-DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Center for Tumor Diseases, Heidelberg
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, PharmaMar, German Cancer Research Center
- Responsible party
- Sponsor
- Investigators
- Stefan Froehling, MD, Principal investigator, NCT / DKFZ Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03127215
- Sponsor's protocol ID
- NCT-2017-0417
- Acronym
- NCT-PMO-1603
- Status last verified
- Aug 2023
- First submitted
- 31 Mar 2017
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03127215
- Acronym / sponsor ID
- NCT-PMO-1603 / NCT-2017-0417
- Conditions
- Cancers With DNA Repair-Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- National Center for Tumor Diseases, HeidelbergUniversity, hospital or other
- Collaborators
- AstraZeneca, PharmaMar, German Cancer Research Center
- Study start
- 25 Oct 2018 (actual)
- Primary completion
- 19 Dec 2023 (actual)
- Study completion
- 19 Dec 2023 (actual)
- First posted
- 25 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized
| Arm | Type | Receives |
|---|---|---|
| Arm E: Olaparib / Trabectedin | Experimental | Drug: Olaparib, Drug: TrabectedinOlaparib / Trabectedin |
| Arm C: Physician's choice | Other | Drug: Physician's choicePhysician's choice |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaparibOlaparib 150 mg tablet | Drug | Arm E: Olaparib / Trabectedin |
| Physician's choicetreatment according to current guidelines | Drug | Arm C: Physician's choice |
| TrabectedinTrabectedin 1.1mg/m² infusional solution | Drug | Arm E: Olaparib / Trabectedin |
Primary outcome
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.
4 secondary outcomes
Overall survival
Time frame: Time from first administration of the IMP to time death from any cause until end of study (2.5 years)
Incidence of Treatment-Emergent Adverse Events
Time frame: Time from first administration of the IMP to subjects end of trial (approximately month 6)
Patient reported outcomes
Time frame: Before the first (week 0), at the third (week 8), and after the fifth treatment cycle (week 16)
Tumor response rate
Time frame: At week 16 (after 5 cycles of study medication)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Froehling, MD principal investigator
NCT / DKFZ Heidelberg
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Olaparib, Physician's choice and Trabectedin in people with Cancers With DNA Repair-Deficiency, run by National Center for Tumor Diseases, Heidelberg at 9 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Control Rate (time frame: At week 16 (after 5 cycles of study medication)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.