Open, non-controlled, parallel cohorts, multicenter, phase 2a trial for the evaluation of the antitumor activity of an IMP single agent and in combination with chemotherapy in patients with locally advanced or metastatic colorectal cancer.
CASE STUDY TYPE
Interventional clinical trial in Oncology (Phase II)
BACKGROUND
Colorectal Cancer (CRC) is the second most commonly diagnosed cancer in Europe. Advanced and metastatic CRC remain unmet need diseases, with few therapeutic options beyond 2-3 lines of therapy. The median survival for patients with metastatic CRC is around 30 months. Anti-Müllerian hormone receptor II (AMHRII) expression is restricted to really small number of normal tissues, but has been shown to be over-expressed in around two thirds of gynecological tumors.
This has led to the development a new investigational medicinal product (IMP), an antibody targeting the AMHRII that had demonstrated in a phase I study in advanced gynecological cancers excellent tolerability profile associated with hints of activity. Recently it has been suggested that more than three quarters of colorectal tumors bear the AMHRII receptor at the tumoral cell membrane.
The aim of this phase 2a trial was to evaluate the antitumor activity of the new IMP as single agent and in combination with trifluridine/tipiracil in previously treated patients suffering from refractory advanced or metastatic colorectal cancer.
METHODS
This was a multinational, multicenter, open, non-controlled trial with a parallel group design. Patients suffering from confirmed locally advanced or metastatic colorectal cancer were considered for inclusion and include in either Cohort I (IMP alone) or Cohort II (IMP in combination with Trifluridine/Tipiracil).
OBJECTIVES
CO-PRIMARY OBJECTIVES
- To evaluate the anti-tumor activity of the IMP single agent and in combination with trifluridine/tripiracil in locally advanced and metastatic colorectal cancers (CRC).
EXPLORATORY OBJECTIVES
- Document potential pharmacodynamics effect of the IMP in immune blood cells;
- Investigate potential relationship between AMRHII levels and clinical outcomes;
- Identify potential other biomarkers predictive of tumor response to the IMP.
SECONDARY OBJECTIVES
- Assess the pharmacokinetic parameters;
- Characterize the safety profile in monotherapy and in combination with chemotherapy;
- Evaluate anti-tumor activity;
- Assess the potential immunogenicity.
SCIENTIFIC and DATA vALORISATION
- Poster presentation at ASCO 2019
- Poster presentation at WCGIC 2019
Key factors of success
- ICTA’s expertise in risk management and site contract management
- ICTA’s capability to propose innovative solutions for uncommon projects
- ICTA’s ability to manage several stakeholders to accurately perform all study procedures and exams aligned with the study protocol
LESSONS LEARNED to speed up the start-up phase of the next study
- The importance of close collaboration and communication between ICTA, Sponsor and all key stakeholders, including a commonly agreed communication plan
- The value of optimal project coordination, with careful attention given to agreed timelines
- Close management of ICTA resources to allow proactive and reactive actions/responses, including trial status progress report.
CHALLENGES
| KEY CHALLENGES | ICTA’s SOLUTIONS | ICTA’s ACHIEVEMENTS |
|---|---|---|
| Short recruitment period | Feasibility handled in 2 countries and focused on KoL. Patients potential per site endorsed at the earliest in order to increase the number of sites if needed | Targeted patient sample size achieved before the end of 6-month recruitment period |
| Several stakeholders involved in the laboratory sample handling (sites, CRO, logistician, 5 central labs) High risk of misunderstanding and errors | Communication plan validated by each stakeholder at the start-up phase Regular reminders to the sites about the request of pick-up of samples | Set up of adequate logistics and related trackers with all central labs |
| Financial contract backlog Huge delay in contract negotiation due to site burden. High risk of postponing SIV and patient recruitment start | Contract negotiations started at the earliest. Flexible and fast in the negotiations. Contract negotiations to be started in parallel of preparation of regulatory submissions. | 100% of active sites within planned timelines |
| Risk of material incompatibility for IMP infusion (pump, tubing, bags,… | Provision of uniform infusion pumps to sites. | Material available on site checked from PSV phase |