Maintenance With Niraparib In Patients With Advanced Urothelial Cancer After 1st-line Platinum-based Chemotherapy

NCT03945084 | Completed Phase 2 FDA Drug

• 1 other identifier: Meet-URO 12
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 20

Brief Summary

This is a 2-arm, prospective, randomized (2:1 ratio), open-label, multi-centre, phase II study conducted in patients affected by unresectable, locally advanced or metastatic urothelial cancer receiving niraparib plus best supportive care versus best supportive care as maintenance therapy after a first-line platinum-based chemotherapy. The primary objective of the trial is to evaluate the efficacy of niraparib plus Best Supportive Care (BSC) vs. BSC alone, as maintenance treatment, in terms of prolongation of progression-free survival (PFS), in patients with locally advanced or metastatic urothelial cancer that obtained disease control (objective response or stable disease) with first-line platinum-based chemotherapy.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is defined as the time from the date of randomization to the earlier date of assessment of progression, or death by any cause in the absence of progression. Progression will be assessed following Response Evaluation Criteria In Solid Tumors (RECIST) criteria ( v.1.1 ), using investigator's review.

  Up to 3 years

Secondary Outcomes (6)

• Objective response rate (ORR)

  Up to 3 years

• Duration of response (DoR)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

• Progression-free survival at 6 months

  6 months

• Treatment-emergent adverse events (TEAEs)

  Up to 3 years

Other Outcomes (2)

• BReast CAncer gene (BRCA) mutation status (exploratory)

  Assessed on blood sample collected at baseline

• Homologous Recombination Deficiency (HRD) status (exploratory)

  Assessed on tumor tissue collected at baseline

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Patients assigned to experimental arm will receive Niraparib 300 mg or 200 mg daily (based on weight and platelet count) plus best supportive care (BSC), in 28-day cycles, until disease progression or unacceptable toxicity or death.

Drug: Niraparib; Other: Best supportive care

Control Arm

OTHER

Patients assigned to control arm will receive best supportive care alone, until disease progression or death.

Other: Best supportive care

Interventions

Niraparib DRUG

Niraparib will be administered as a flat-fixed, continuous daily dose: ≥77 kg and ≥150,000 µL: 300 mg (3 X 100 mg capsules) daily \<77 kg or \<150,000 µL: 200 mg (2 X 100 mg capsules) daily\* \* For patients whose starting dose is 2 capsules once daily, escalation to 3 capsules once daily will be permitted if no treatment interruption or discontinuation will be required during the first 2 cycles of therapy

Also known as: Zejula

Experimental Arm

Best supportive care OTHER

In both treatment arms, Best Supportive Care (BSC) is defined as a comprehensive assessment of symptoms, with timely application of symptom control measures, in order to maximize patient's quality of life. BSC does not include any active antitumoral treatment, and will be given according to local guidelines and the normal practice of each participating institution. BSC will include use of opioid analgesics, other supportive drugs, radiotherapy, administered with the exclusive aim of improving tumor symptoms (e.g. pain, haematuria, etc.), according to Investigator's judgment.

Control Arm; Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have histologically/cytologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium (transitional cell carcinoma either pure or mixed histology)
• Measurable disease (per RECIST v1.1) prior to the start of first-line chemotherapy
• Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of platinum containing regimen (cisplatin or carboplatin)
• No evidence of progressive disease following completion of first-line chemotherapy (i.e., ongoing complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1 guidelines )
• Patients must be enrolled within 4 weeks of scans demonstrating stable disease/partial-complete response and no more than 6 weeks after receiving the last standard chemotherapy dose
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Participant must be ≥ 18 years of age
• Participant must have adequate bone marrow and organ 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
• Participant receiving corticosteroids is eligible if their dose is stable for least 4 weeks prior to initiating protocol therapy.

You may not qualify if:

• Participant must not be simultaneously enrolled in any interventional clinical trial
• Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
• Participant must not have 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.
• Participant must not have received radiation therapy encompassing \>20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
• Participant must not have a known hypersensitivity to niraparib components or excipients.
• Participant must not have been treated previously with a known PARP inhibitor agent
• Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
• Participant must not have 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.
• Participant must not have experienced any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks.
• Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, 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
• Participant must not have a diagnosis of any other malignancy within 2 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms.
• Participant must not have history of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan. However treated, stable and asymptomatic brain metastases are allowed.

Sponsors & Collaborators

• University of Turin, Italy: lead
• Tesaro, Inc.: collaborator

Study Sites (20)

Azienda Sanitaria Locale CN2 - Alba e Bra

Alba, Italy

Location

Azienda USL Toscana Sud Est, Ospedale San Donato

Arezzo, Italy

Location

Istituto Tumori Giovanni Paolo II - IRCCS

Bari, Italy

Location

Presidio Ospedaliero Senatore A.Perrino

Brindisi, Italy

Location

Azienda Ospedaliero-Universitaria

Cagliari, Italy

Location

Azienda Ospedaliera Cannizzaro

Catania, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS

Meldola, Italy

Location

Istituto Nazionale Tumori IRCCS

Milan, Italy

Location

Istituto Nazionale Tumori - Fondazione G.Pascale IRCCS

Napoli, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, Italy

Location

ASL Piacenza, Dipartimento Oncologico

Piacenza, Italy

Location

Azienda Ospedaliero-Universitaria Pisana, Ospedale Santa Chiara

Pisa, Italy

Location

Ausl - Irccs

Reggio Emilia, Italy

Location

Irccs Crob

Rionero in Vulture, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Roma, Italy

Location

Campus Biomedico

Roma, Italy

Location

SCDU Oncologia Medica, AO Ordine Mauriziano

Torino, Italy

Location

Presidio Ospedaliero Santa Chiara - APSS

Trento, Italy

Location

AOU Santa Maria della Misericordia

Udine, Italy

Location

Related Links

• Description of the results presented at ASCO GU 2022

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

niraparib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Massimo Di Maio, MD

  Department of Oncology, University of Turin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medical Oncology, Department of Oncology

Model Details: 2-arm, prospective, randomized (2:1 ratio), open-label, multi-centre, phase II study

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 10, 2019
• Study Start: August 27, 2019
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: May 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (20)