NCT03945084

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

A Phase II, Randomized, Trial of Niraparib Versus Best Supportive Care as Maintenance Treatment In Patients With Locally Advanced Or Metastatic Urothelial Cancer Whose Disease Did Not Progress After First-line Platinum-based Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: University of Turin, Italy · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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. Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors sensitivity is based on the presence of truncating and missense mutations in genes associated with the homologous recombination pathways. In The Cancer Genome Atlas dataset approximately 34% of bladder urothelial carcinoma harbored these mutations. Furthermore, in this study we plan to select a population potentially sensible to niraparib, by enrolling patients responding to platinum, indeed we know that there is a cross-sensitivity and a cross-resistance between platinum drugs and PARP inhibitors in urothelial carcinoma. PFS is commonly adopted as primary endpoint in randomized phase II trials. Randomized design for phase II trials has been increasingly adopted in recent years, to allow a formal comparison between experimental and standard treatment. This should lead to a better interpretation of the results obtained with the experimental treatment, that are in most cases difficult to interpret in the absence of controls. The sample size of the study is calculated with "relaxed" statistical criteria. The study design will verify if the experimental treatment (Niraparib) is promising enough to warrant a phase 3 trial for efficacy compared to observation. A total of 65 PFS events are needed to provide 80% power to detect an hazard ratio (HR) of 0.57 (1.75), corresponding to a median increase in progression-free survival from 4 to 7 months, with one-tailed alpha 0.1. With an accrual duration of 24 months, and additional 6 months of follow up after the completion of recruitment, 77 patient need to be randomized (26 assigned to control arm and 51 assigned to experimental arm) to obtain the 65 events needed. Sample size of the phase II trial is too small to plan a formal analysis of interaction of treatment efficacy with type of response at first line treatment (i.e. objective response vs. stable disease). However, type of response to first line treatment will be among stratification factor for randomization, so the 2 treatment groups will be balanced. Exploratory subgroup analysis of treatment efficacy in patient who have obtained objective response with first line and in patients who have obtained stable disease with first line will be performed.

Conditions

• Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Niraparib	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
OTHER	Best supportive care	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.

Timeline

• Start date: 2019-08-27
• Primary completion: 2021-09-01
• Completion: 2021-09-01
• First posted: 2019-05-10
• Last updated: 2022-05-23

Locations

20 sites across 1 country: Italy

Regulatory

• FDA-regulated drug study