Newton Study (NEW Dosing MainTenance Therapy Ovarian CaNcer)

NCT03891576 | Terminated Phase 2 FDA Drug

• 1 other identifier: IRFMN-OVA-7814
• Study Type: interventional
• Target: 83
• Locations: 2 countries
• Sites: 12

Brief Summary

This study evaluates whether the adoption of the RADAR dosing strategy could further reduce treatment related toxicities improving the safety profile of niraparib.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Keywords

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Platinum Senitive; Recurrent Cancer; Niraparib; Thrombocytopenia; Neutropenia; Anemia; RADAR dosing; Maintenance Therapy; PARP-inhibitor

Outcome Measures

Primary Outcomes (1)

• Safety: Occurrence of grade ≥3 thrombocytopenia

  Rate of patients experiencing a grade ≥3 thrombocytopenia during the first three cycles

  3 months

Secondary Outcomes (14)

• Safety: Occurrence of grade ≥ 3 thrombocytopenia

  6 months

• Safety: Maximum toxicity grade

  Up to two years after the last patient enrolled

• Safety: Grade 3-4 toxicities

  Up to two years after the last patient enrolled

• Safety: SAE

  Up to two years after the last patient enrolled

• Safety: Number of patients with at least a SAE

  Up to two years after the last patient enrolled

Study Arms (3)

Niraparib 200 mg

EXPERIMENTAL

Niraparib will be administered every day as oral at a fixed dose of 200 mg

Drug: Niraparib

Niraparib 300 mg

ACTIVE COMPARATOR

Niraparib will be administered every day as oral at a fixed dose of 300 mg

Drug: Niraparib

Niraparib 200mg/300mg

OTHER

Niraparib will be administered every day as oral at a fixed dose of 200 mg or 300 mg

Drug: Niraparib

Interventions

Niraparib DRUG

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.

Also known as: Zejula

Niraparib 200 mg; Niraparib 200mg/300mg; Niraparib 300 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• North Eastern German Society of Gynaecological Oncology: collaborator

Study Sites (12)

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

University Hospital Dresden

Dresden, Germany

Location

Kliniken Essen Mitte

Essen, Germany

Location

ASST degli Spedali Civili di Brescia

Brescia, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Istituto Nazionale dei Tumori

Milan, Italy

Location

Ospedale San Gerardo

Monza, Italy

Location

Istituto Oncologico Veneto (IOV)

Padua, Italy

Location

AO Arcispedale Santa Maria Nuova

Reggio Emilia, Italy

Location

Policlinico Umberto I, Università di Roma "La Sapienza"

Roma, Italy

Location

AO Ordine Mauriziano

Torino, Italy

Location

AOU Città della Salute e della Scienza di Torino - Ospedale Sant'Anna

Torino, Italy

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Recurrence; Thrombocytopenia; Neutropenia; Anemia

Interventions

niraparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Agranulocytosis; Leukopenia; Leukocyte Disorders

Study Officials

• Nicoletta Colombo, MD

  Istituto Europeo di Oncologia (IEO) - Milan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 27, 2019
• Study Start: November 13, 2019
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: January 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); IT (9)