In short
- Patients with bladder cancer face limited treatment options when the standard of care fails. Recurrence is common, and patients require repeated surgical interventions, local chemotherapy, or immunotherapy that may result in complications; all taking a toll on patients and their families
- The need for effective alternative therapies is urgent. Each delay can mean lost time for patients waiting for a new chance at remission
- Determined to accelerate access to a new therapy for bladder cancer, a sponsor launched a program and partnered with PSI to help bring it to patients as swiftly and safely as possible
- The close collaboration and shared determination between the sponsor and PSI ensured every obstacle that arose was overcome
- The result: FDA approval for an innovative bladder cancer therapy and a meaningful advancement for patients
- True partnerships go beyond contracts. They’re built on mutual commitment, shared goals, and continuous learning — bringing out the best in both the sponsor and the CRO, and ultimately, delivering hope to patients who need it most
Background
The main types of bladder cancer are urothelial carcinoma (the most prevalent), squamous cell carcinoma and adenocarcinoma. Urothelial carcinoma is classified by invasiveness:
- Non-muscle invasive bladder cancer (NMIBC) its heterogeneous nature results in significant variation in risk of recurrence, prognosis, and progression [1]. While the gold standard treatment, TURBT followed by BCG therapy, is well-established and is effective in patients who respond, NMIBC’s high rates of recurrence and progression mean this vulnerable patient population requires alternative treatment options. Regular, and potentially increasing, visits to the hospital for invasive monitoring and surgeries [2] are burdensome for those patients with recurrence.
- Muscle-invasive bladder cancer (MIBC) arise through pathways distinct to NMIBC [3]. Treatment for MIBC generally consists of TURBT (to determine extent of metastasis) and radical cystectomy with prior neoadjuvant chemotherapy; following cystectomy, treatment consists of adjuvant chemotherapy or promising immune checkpoint inhibitors [3].
A significant drive to develop treatments for patients with bladder cancer, and those at risk of recurrence, has led to advances; however, a substantial proportion of patients remain underserved. Additionally, while single-arm trials for patients with bladder cancer are common, due to ethical concerns and the alternative to placebo being a radical cystectomy (and associated QoL reductions), these trial designs also have their own difficulties – paramount being the ability to generate appropriate data so new drugs can be approved [2]. Patients with bladder cancer need new, effective, alternative therapies to the SoC, and it is important that these therapies are approved for use as soon as possible.
The program
A biopharma sponsor needed a reliable partner to run their bladder cancer program. PSI quickly completed patient recruitment; however, alternative development plans were needed following positive data. The sponsor and PSI quickly pivoted to ensure the program remained on track.
Challenges along the way
Challenge 1: Difficulties enrolling patients from certain regions – unresolved at first, but then resolved
While one region was originally targeted, extensive discussion with regulatory authorities and sites revealed that it wasn’t the optimal choice at the time. Consequently, the sponsor and PSI pivoted, refocusing recruitment efforts on other global sites, thus ensuring timely enrollment despite this initial setback.
At a later stage of the program, the sponsor capitalized on PSI’s expertise and revisited the previously challenging option, which had since become less challenging following changes in eligibility and a change in the region’s regulatory requirements. With PSI’s recent experience in similar studies, and strong relationships with sites and local authorities, enrollment was much more straightforward this time around. Ultimately, the strategic approach and tenacity from the sponsor and PSI led to successful enrollment – with one site from the region becoming the top performing recruiter overall.
Challenge 2: Data challenges – resolved
Following communication with the FDA, the sponsor initiated a structural change to collect additional data, which necessitated additional training for sites. PSI provided individual CRA support to sites to communicate these changes in person. Supervised monitoring visits, training sessions, and one-on-one guidance meetings drove sites to quickly understand and adopt the new EDC and ensured that data entry remained accurate and valid.
Challenge 3: Site inspections – resolved
During the program, the FDA selected three top-enrolling sites for inspection. To support the sites with their inspection, PSI proactively provided additional on-site support, including mentorship to ensure that sites were comfortable with what was expected of them during the inspection, and training to maintain the standards at the sites. Consequently, one site received no comments (NAI) from the FDA, and the other two sites had voluntary actions (VAI).
The outcome
The approach that the sponsor and PSI employed to ensure the program’s continuous success meant that PSI was not only able to meet the prespecified milestones on time across the program but was also able to adapt and be flexible when the sponsor identified opportunities where updating the milestones was beneficial. The results-oriented and consistent team at PSI shared the sponsor’s drive in ensuring the on-time delivery at all stages of the trials. The sponsor’s treatment for bladder cancer was approved by the FDA.
Your unwavering focus on quality and partnership has made a meaningful and lasting impact, and we feel privileged to have worked alongside you.
As a result, the sponsor also decided to move another clinical development program from another CRO to PSI.
Key takeaways
Committing to a long-term program of trials with a single CRO can be daunting, especially in challenging indications. The traditional advice is that diversification is safer, but, sometimes concentrating all efforts on a single, proven, experienced, high-potential opportunity can lead to a greater reward than spreading time and resources across lesser opportunities. Committing with the right CRO enables continuous support, the proactive implementation of lessons learned, and on-time delivery from trial setup and initiation, all the way to DBL, CSR, and FDA approval. Having to build experience and expertise over and over across multiple CROs takes time away from important research and development. Choose wisely.
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Abbreviations
BCG, Bacillus Calmette-Guérin;
CRA, clinical research associate;
CRO, contract research organization;
, Clinical Study Report,
CTR, Clinical Trials Regulation;
DBL, database lock;
EDC, electronic data capture;
FDA, Food and Drug Administration;
MIBC, muscle-invasive bladder cancer;
NAI, No Action Indicated;
NMIBC, non-muscle invasive bladder cancer;
QoL, quality of life;
SoC, standard of care;
TURBT, Transurethral Resection of Bladder Tumor;
VAI, Voluntary Action Indicated.
References
1. Matulewicz, R.S. and Steinberg, G.D., Non-muscle-invasive Bladder Cancer: Overview and Contemporary Treatment Landscape of Neoadjuvant Chemoablative Therapies. Rev Urol, 2020. 22(2): p. 43–51.
2. Dobruch, J. and Oszczudłowski, M., Bladder Cancer: Current Challenges and Future Directions. Medicina (Kaunas), 2021. 57(8).
3. Lopez-Beltran, A., et al., Advances in diagnosis and treatment of bladder cancer. Bmj, 2024. 384: p. e076743.
