Newton Study (NEW Dosing mainTenance Therapy Ovarian caNcer) (Newton)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma
• Intervention / Treatment: Drug: Niraparib

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elena Biagioli; Phone Number: +390239014650; Email: newton@marionegri.it
• Study Contact Backup: Name: Roldano Fossati; Email: newton@marionegri.it

Study Locations

• Germany
  • Berlin, Germany
    • Charite - Universitatsmedizin Berlin
  • Dresde, Germany
    • University Hospital Dresden
  • Essen, Germany
    • Kliniken Essen Mitte
• Italy
  • Brescia, Italy
    • ASST degli Spedali Civili di Brescia
  • Lecco, Italy
    • ASST di Lecco
  • Milan, Italy
    • Istituto Europeo di Oncologia
  • Monza, Italy
    • Ospedale San Gerardo
  • Padova, Italy
    • Istituto Oncologico Veneto (IOV)
  • Reggio Emilia, Italy
    • AO Arcispedale Santa Maria Nuova
  • Roma, Italy
    • Policlinico Umberto I, Università di Roma "La Sapienza"
  • Torino, Italy
    • AO Ordine Mauriziano
  • Torino, Italy
    • AOU Città della Salute e della Scienza di Torino - Ospedale Sant'Anna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 18 years of age or older, female, any race
2. Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
3. High grade (or grade 3) serous histology or known to have gBRCAmut
4. 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)
5. Has responded to the last platinum line (PR or CR)
6. No more than 8 weeks have elapsed from completion of the last platinum regimen and the patient is still not progressing after response
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1

8. Adequate bone marrow, kidney and liver function, defined as follows:

   1. Absolute neutrophil count ≥ 1,500/µL
   2. Platelets ≥ 100,000/µL
   3. Hemoglobin ≥ 9 g/dL
   4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
   5. Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
   6. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
9. Patient receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
10. 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.
11. Patient must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
12. Patient must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
13. Patients must have normal blood pressure or adequately treated and controlled hypertension. (i.e. systolic BP ≤ 140 mmHg and diastolic BP ≤ 90 mmHg)

Exclusion Criteria:

1. Patient simultaneously enrolled in any interventional clinical trial
2. Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
3. Patient with known, symptomatic brain or leptomeningeal metastases
4. Patient with immunocompromised status
5. Patient with known active hepatic disease
6. Prior treatment with a known PARP inhibitor
7. Patient who has had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
8. 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.
9. Patient has had radiation therapy encompassing >20% of the bone marrow within 2 weeks prior to day 1 of protocol therapy
10. Patient has had any radiation therapy within 1 week prior to day 1 of protocol therapy.
11. Patient with known hypersensitivity to niraparib components or excipients.
12. Patient has received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
13. 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.
14. 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.
15. Patient with any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
16. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Niraparib 200 mg; Niraparib will be administered every day as oral at a fixed dose of 200 mg	Drug: Niraparib; 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.; Other Names: Zejula
Active Comparator: Niraparib 300 mg; Niraparib will be administered every day as oral at a fixed dose of 300 mg	Drug: Niraparib; 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.; Other Names: Zejula
Other: Niraparib 200mg/300mg; Niraparib will be administered every day as oral at a fixed dose of 200 mg or 300 mg	Drug: Niraparib; 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.; Other Names: Zejula

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Occurrence of grade ≥3 thrombocytopenia	Rate of patients experiencing a grade ≥3 thrombocytopenia during the first three cycles	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Occurrence of grade ≥ 3 thrombocytopenia	Rate of patients experiencing a grade ≥3 thrombocytopenia during the first six cycles	6 months
Safety: Maximum toxicity grade	Maximum toxicity grade experienced by each patient, for each toxicity, according to NCI-CTCAE v. 4.03	Up to two years after the last patient enrolled
Safety: Grade 3-4 toxicities	Patient experiencing grade 3-4 for each toxicity	Up to two years after the last patient enrolled
Safety: SAE	Type, frequency and nature of SAEs	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	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	Up two years after last patient enrolled
Safety: Number of patients with at least a SUSAR	Number of patients with at least a SUSAR	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	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	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	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	Up to two years after the last patient enrolled
Compliance	Number of administered cycles	Up to two years after the last patient enrolled
Compliance	Frequency and reasons for drug discontinuation and treatment modification	Up to two years after the last patient enrolled
Compliance	Dose intensity	Up to two years after the last patient enrolled

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: North Eastern German Society of Gynaecological Oncology
• Investigators: Principal Investigator: Nicoletta Colombo, MD, Istituto Europeo di Oncologia (IEO) - Milan

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Anemia; Niraparib; Ovarian Cancer; Recurrent Cancer; Neutropenia; Maintenance Therapy; PARP-inhibitor; Thrombocytopenia; Fallopian Tube Cancer; Primary Peritoneal Cancer; Platinum Senitive; RADAR dosing
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Niraparib
• Other Study ID Numbers: IRFMN-OVA-7814

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes