Ovarian CancerPhase 2NewtonNCT03891576
Newton Study (NEW Dosing MainTenance Therapy Ovarian CaNcer)
A Phase 2 study testing Niraparib in people with Ovarian Cancer and Fallopian Tube Cancer, run by Mario Negri Institute for Pharmacological Research at 12 sites in 2 countries.
Trial summary
This study evaluates whether the adoption of the RADAR dosing strategy could further reduce treatment related toxicities improving the safety profile of niraparib. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma
- What is being tested?
- Niraparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 13 Nov 2019to 31 Aug 2024
- 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 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 years of age or older, female, any race
- Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
- High grade (or grade 3) serous histology or known to have gBRCAmut
- Has received at least 2 previous lines of platinum-containing therapy (not necessarily consecutive), and has disease that was considered platinum sensitive following the penultimate platinum line (more than 6-months period between penultimate platinum regimen and progression of disease)
- Has responded to the last platinum line (PR or CR)
- No more than 8 weeks have elapsed from completion of the last platinum regimen and the patient is still not progressing after response
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- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- Adequate bone marrow, kidney and liver function, defined as follows:
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9 g/dL
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
- Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
- Patient receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
- Patient must have a negative urine or serum pregnancy test within 7 days prior to taking study treatment if childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment or use adequate barrier methods throughout the study. Non-childbearing potential is defined as follows (by other than medical reasons): ≥45 years of age and has not had menses for >1 year; patients with amenorrhea for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation; Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment.
- Patient must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
- Patient must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
- Patients must have normal blood pressure or adequately treated and controlled hypertension. (i.e. systolic BP ≤ 140 mmHg and diastolic BP ≤ 90 mmHg)
Who cannot join
- Patient simultaneously enrolled in any interventional clinical trial
- Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
- Patient with known, symptomatic brain or leptomeningeal metastases
- Patient with immunocompromised status
- Patient with known active hepatic disease
- Prior treatment with a known PARP inhibitor
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- Patient who has had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
- Patient who has received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
- Patient has had radiation therapy encompassing >20% of the bone marrow within 2 weeks prior to day 1 of protocol therapy
- Patient has had any radiation therapy within 1 week prior to day 1 of protocol therapy.
- Patient with known hypersensitivity to niraparib components or excipients.
- Patient has received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
- Patient has received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
- Patient has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
- Patient with any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
- Patient with a serious, uncontrolled medical disorder. Examples include, but are not limited to, nonmalignant systemic disease, active, uncontrolled infection, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Italy9 sites
ASST degli Spedali Civili di Brescia
Brescia
Istituto Europeo di Oncologia
Milan
Istituto Nazionale dei Tumori
Milan
Ospedale San Gerardo
Monza
Istituto Oncologico Veneto (IOV)
Padova
AO Arcispedale Santa Maria Nuova
Reggio Emilia
Policlinico Umberto I, Università di Roma "La Sapienza"
Roma
AO Ordine Mauriziano
Torino
AOU Città della Salute e della Scienza di Torino - Ospedale Sant'Anna
Torino
Germany3 sites
Charité - Universitätsmedizin Berlin
Berlin
University Hospital Dresden
Dresden
Kliniken Essen Mitte
Essen
About this study
Official title: A Multicenter, Open-label Phase II Trial of a New Customized Dosing (RADAR Dosing) of Niraparib As Maintenance Therapy in Platinum Sensitive Ovarian, Fallopian Tube or Primary Peritoneal Recurrent Cancer Patients
This study evaluates whether the adoption of the RADAR dosing strategy could further reduce treatment related toxicities improving the safety profile of niraparib.
- Being tested
- Niraparib
- Keywords
- Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Platinum Senitive, Recurrent Cancer, Niraparib, Thrombocytopenia, Neutropenia, Anemia, RADAR dosing, Maintenance Therapy, PARP-inhibitor
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms, Recurrence, Thrombocytopenia, Neutropenia, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors.
| Study group | Role | What they receive |
|---|---|---|
| Niraparib 200 mg | Experimental | Niraparib will be administered every day as oral at a fixed dose of 200 mg Receives: Drug: Niraparib |
| Niraparib 300 mg | Active comparator | Niraparib will be administered every day as oral at a fixed dose of 300 mg Receives: Drug: Niraparib |
| Niraparib 200mg/300mg | Other | Niraparib will be administered every day as oral at a fixed dose of 200 mg or 300 mg Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Occurrence of grade ≥3 thrombocytopenia
Rate of patients experiencing a grade ≥3 thrombocytopenia during the first three cycles
Measured: 3 months
Secondary outcomes (14)
Safety: Occurrence of grade ≥ 3 thrombocytopenia
Rate of patients experiencing a grade ≥3 thrombocytopenia during the first six cycles
Measured: 6 months
Safety: Maximum toxicity grade
Maximum toxicity grade experienced by each patient, for each toxicity, according to NCI-CTCAE v. 4.03
Measured: Up to two years after the last patient enrolled
Safety: Grade 3-4 toxicities
Patient experiencing grade 3-4 for each toxicity
Measured: Up to two years after the last patient enrolled
Safety: SAE
Type, frequency and nature of SAEs
Measured: Up to two years after the last patient enrolled
Safety: Number of patients with at least a SAE
Number of patients with at least a SAE
Measured: Up to two years after the last patient enrolled
Safety: Number of patients with at least a SADR
Number of patients with at least a SADR
Measured: Up two years after last patient enrolled
Safety: Number of patients with at least a SUSAR
Number of patients with at least a SUSAR
Measured: Up two years after last patient enrolled
Efficacy: PFS-6
PFS rate at 6 months, defines as the proportion of patients alive and free from progression at 6 months after randomization
Measured: 6 months
Efficacy: PFS
PFS, defined as the time from the date of treatment randomization to the date of first documentation of progression or death whichever occurs first
Measured: Up two years after last patient enrolled
Efficacy: OS
OS at 24 months, defined as the rate of patients who are alive at 24 months from randomization
Measured: Up two years after last patient enrolled
Pharmacokinetic
Trough level of niraparib concentration at steady state (Css) and peak level at 2 hours after dosing
Measured: Up to two years after the last patient enrolled
Compliance
Number of administered cycles
Measured: Up to two years after the last patient enrolled
Compliance
Frequency and reasons for drug discontinuation and treatment modification
Measured: Up to two years after the last patient enrolled
Compliance
Dose intensity
Measured: Up to two years after the last patient enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2019
- Study start13 Nov 2019
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Why it stopped: Low accrual rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe sponsor's other registered studies.
- 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
- This is a study built up by a randomized and a no-randomized part. Randomized part: Patients who either have a baseline body weight ≥58 and \<77kg, or have a baseline body weight ≥77kg and baseline platelet count \<150,000/µL (named as restricted population) will be randomly assigned to receive RADAR dosing or the SmPC dosing. Randomization ratio will be 1:1 and will be based on a minimization procedure accounting for the following factors: i. platinum sensitivity; ii. use of bevacizumab in conjunction with the penultimate platinum based therapy; iii. best response (complete or partial) during the last platinum regimen. No-randomized part: Patients with weight \<58 or ≥77kg and baseline platelet count ≥150,000/µL will be enrolled into the study but not randomized.
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- North Eastern German Society of Gynaecological Oncology
- Responsible party
- Sponsor
- Investigators
- Nicoletta Colombo, MD, Principal investigator, Istituto Europeo di Oncologia (IEO) - Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03891576
- Sponsor's protocol ID
- IRFMN-OVA-7814
- Acronym
- Newton
- Status last verified
- Jan 2025
- First submitted
- 25 Mar 2019
- Last updated
- 17 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Colombo N, Parma G, Tasca G, Di Palma MP, Tognon G, Lissoni AA, Fossati R, Carlucci L, Zucchetti M, Matteo C, Ferrero A, Bologna A, Mantiero M, Wimberger P, Katsaros D, Tomao F, Galli F, Lapresa M, Guarneri V, Ficarelli S, Canova S, Derio S, Girardi F, Zizioli V, Katrini J, Massa D, Rulli E, Biagioli E; NEWTON study group. Rational adjustment of dose to reduce adverse reactions (RADAR) in patients with platinum-sensitive recurrent ovarian cancer: Results from the phase II NEWTON trial (ENGOT-ov49). Eur J Cancer. 2026 May 15;239:116685. doi: 10.1016/j.ejca.2026.116685. Epub 2026 Mar 27.
PubMed 41950571
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label Phase II Trial of a New Customized Dosing (RADAR Dosing) of Niraparib As Maintenance Therapy in Platinum Sensitive Ovarian, Fallopian Tube or Primary Peritoneal Recurrent Cancer Patients
- ClinicalTrials.gov ID
- NCT03891576
- Acronym / sponsor ID
- Newton / IRFMN-OVA-7814
- Keywords
- Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Platinum Senitive, Recurrent Cancer, Niraparib, Thrombocytopenia, Neutropenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual rate
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Collaborators
- North Eastern German Society of Gynaecological Oncology
- Study start
- 13 Nov 2019 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 27 Mar 2019 (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.
This study evaluates whether the adoption of the RADAR dosing strategy could further reduce treatment related toxicities improving the safety profile of niraparib.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is a study built up by a randomized and a no-randomized part. Randomized part: Patients who either have a baseline body weight ≥58 and <77kg, or have a baseline body weight ≥77kg and baseline platelet count <150,000/µL (named as restricted population) will be randomly assigned to receive RADAR dosing or the SmPC dosing. Randomization ratio will be 1:1 and will be based on a minimization procedure accounting for the following factors: i. platinum sensitivity; ii. use of bevacizumab in conjunction with the penultimate platinum based therapy; iii. best response (complete or partial) during the last platinum regimen. No-randomized part: Patients with weight <58 or ≥77kg and baseline platelet count ≥150,000/µL will be enrolled into the study but not randomized.
| Arm | Type | Receives |
|---|---|---|
| Niraparib 200 mg | Experimental | Drug: NiraparibNiraparib will be administered every day as oral at a fixed dose of 200 mg |
| Niraparib 300 mg | Active comparator | Drug: NiraparibNiraparib will be administered every day as oral at a fixed dose of 300 mg |
| Niraparib 200mg/300mg | Other | Drug: NiraparibNiraparib will be administered every day as oral at a fixed dose of 200 mg or 300 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 18 years of age or older, female, any race
- Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
- High grade (or grade 3) serous histology or known to have gBRCAmut
- Has received at least 2 previous lines of platinum-containing therapy (not necessarily consecutive), and has disease that was considered platinum sensitive following the penultimate platinum line (more than 6-months period between penultimate platinum regimen and progression of disease)
- Has responded to the last platinum line (PR or CR)
Key exclusion criteria (16 listed)
- Patient simultaneously enrolled in any interventional clinical trial
- Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
- Patient with known, symptomatic brain or leptomeningeal metastases
- Patient with immunocompromised status
- Patient with known active hepatic disease
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 |
|---|---|---|
| NiraparibAlso: ZejulaNiraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors. | Drug | Niraparib 200 mg, Niraparib 200mg/300mg, Niraparib 300 mg |
Primary outcome
Safety: Occurrence of grade ≥3 thrombocytopenia
Time frame: 3 months
Rate of patients experiencing a grade ≥3 thrombocytopenia during the first three cycles
14 secondary outcomes
Safety: Occurrence of grade ≥ 3 thrombocytopenia
Time frame: 6 months
Safety: Maximum toxicity grade
Time frame: Up to two years after the last patient enrolled
Safety: Grade 3-4 toxicities
Time frame: Up to two years after the last patient enrolled
Safety: SAE
Time frame: Up to two years after the last patient enrolled
Safety: Number of patients with at least a SAE
Time frame: Up to two years after the last patient enrolled
Safety: Number of patients with at least a SADR
Time frame: Up two years after last patient enrolled
Safety: Number of patients with at least a SUSAR
Time frame: Up two years after last patient enrolled
Efficacy: PFS-6
Time frame: 6 months
Efficacy: PFS
Time frame: Up two years after last patient enrolled
Efficacy: OS
Time frame: Up two years after last patient enrolled
Pharmacokinetic
Time frame: Up to two years after the last patient enrolled
Compliance
Time frame: Up to two years after the last patient enrolled
Compliance
Time frame: Up to two years after the last patient enrolled
Compliance
Time frame: Up to two years after the last patient enrolled
Results and safety
The study was stopped early (reason given: Low accrual rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2025.
- Derived from this study: PubMed 41950571Colombo N, Parma G, Tasca G, Di Palma MP, Tognon G, Lissoni AA, Fossati R, Carlucci L, Zucchetti M, Matteo C, Ferrero A, Bologna A, Mantiero M, Wimberger P, Katsaros D, Tomao F, Galli F, Lapresa M, Guarneri V, Ficarelli S, Canova S, Derio S, Girardi F, Zizioli V, Katrini J, Massa D, Rulli E, Biagioli E; NEWTON study group. Rational adjustment of dose to reduce adverse reactions (RADAR) in patients with platinum-sensitive recurrent ovarian cancer: Results from the phase II NEWTON trial (ENGOT-ov49). Eur J Cancer. 2026 May 15;239:116685. doi: 10.1016/j.ejca.2026.116685. Epub 2026 Mar 27.
- Individual participant dataSharing planned: No
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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.
Nicoletta Colombo, MD principal investigator
Istituto Europeo di Oncologia (IEO) - Milan
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib in people with Ovarian Cancer and Fallopian Tube Cancer, run by Mario Negri Institute for Pharmacological Research at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. 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: stopped early, as of the sponsor's last update on 17 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Italy, 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 was stopped early (reason given: Low accrual rate). Results are not available in the source record.
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?
Safety: Occurrence of grade ≥3 thrombocytopenia (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03891576, which also lists 1 linked publication.
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 17 Jan 2025.