Clinical trial NCT03891576: Newton Study (NEW Dosing MainTenance Therapy Ovarian CaNcer)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: North Eastern German Society of Gynaecological Oncology
First posted: 2019-03-27
Enrollment: 83
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety: Occurrence of grade ≥3 thrombocytopenia
timeFrame: 3 months
Secondary outcomes:
measure: Safety: Occurrence of grade ≥ 3 thrombocytopenia
timeFrame: 6 months
measure: Safety: Maximum toxicity grade
timeFrame: Up to two years after the last patient enrolled
measure: Safety: Grade 3-4 toxicities
timeFrame: Up to two years after the last patient enrolled
measure: Safety: SAE
timeFrame: Up to two years after the last patient enrolled
measure: Safety: Number of patients with at least a SAE
timeFrame: Up to two years after the last patient enrolled
measure: Safety: Number of patients with at least a SADR
timeFrame: Up two years after last patient enrolled
measure: Safety: Number of patients with at least a SUSAR
timeFrame: Up two years after last patient enrolled
measure: Efficacy: PFS-6
timeFrame: 6 months
measure: Efficacy: PFS
timeFrame: Up two years after last patient enrolled
measure: Efficacy: OS
timeFrame: Up two years after last patient enrolled
measure: Pharmacokinetic
timeFrame: Up to two years after the last patient enrolled
measure: Compliance
timeFrame: Up to two years after the last patient enrolled
measure: Compliance
timeFrame: Up to two years after the last patient enrolled
measure: Compliance
timeFrame: Up to two years after the last patient enrolled
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Dresde
country: Germany
facility: University Hospital Dresden
city: Essen
country: Germany
facility: Kliniken Essen Mitte
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Monza
country: Italy
facility: Ospedale San Gerardo
city: Padova
country: Italy
facility: Istituto Oncologico Veneto (IOV)
city: Reggio Emilia
country: Italy
facility: AO Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Policlinico Umberto I, Università di Roma "La Sapienza"
city: Torino
country: Italy
facility: AO Ordine Mauriziano
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino - Ospedale Sant'Anna
Study officials:
affiliation: Istituto Europeo di Oncologia (IEO) - Milan
name: Nicoletta Colombo, MD
role: PRINCIPAL_INVESTIGATOR
References: