NCT06569225

Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig in Resectable iCCA

Perioperative Therapy With Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig for Patients With Resectable Intrahepatic Cholangiocarcinoma (iCCA) - A Phase II Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: University Health Network, Toronto · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Biliary tract cancer is a highly aggressive and heterogeneous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (CCA), or the gallbladder (GBC)(1-3). While it accounts for only 0.7% of all malignant tumors and 3% of all gastrointestinal malignancies in adults, both incidence and mortality are increasing. Biliary tract cancers usually present at an advanced stage, with only approximately 20% of patients being diagnosed with an early-stage disease (1, 2, 4). There is a high risk of recurrence post curative radical resection, with 60-70% of patients recurring within 5 years, with 5-year survival of around 25% (1, 2, 5). There is evidence for use of adjuvant chemotherapy with fluoropyrimidine- based regimens as per the BILCAP and ASCOT phase III trials \[(5-7).However, despite advances in adjuvant treatment, recurrence rates after resection of BTC remain high even with adjuvant chemotherapy. For example, in the BILCAP study, 5-year RFS was reported as 33.9% (95% CI: 27.6 to 40.2) (1). Therefore, an unmet need exists to optimize peri-operative treatment to reduce recurrence and improve outcomes in patients with resectable BTC.

Detailed description

The only curative management for iCCA is radical surgical resection. However, less than 35% of patients present with resectable disease at diagnosis, and postoperative recurrence and relapse rates are around 50-70%. Despite advances in diagnostics and therapeutic interventions, prognosis remains poor with an overall 5-year survival of less than 20%.1 The results of the TOPAZ-12 and KEYNOTE-9663 study have established PD-L1 (durvalumab) and PD-1 (pembrolizumab) inhibition in combination with gemcitabine and cisplatin as a new standard of care highlighting the role of immune checkpoint inhibition in advanced biliary tract cancer (BTC). In addition, the combination of Nab-Paclitaxel and gemcitabine, cisplatin has demonstrated efficacy in advanced BTC4. Several clinical trials evaluating the efficacy of neoadjuvant combinational therapy with gemcitabine, cisplatin and PD-L1 inhibition are ongoing (NCT04989218, NCT06050252, NCT04308174). Neoadjuvant treatment in iCCA allows for delivery of treatment pre surgery and can induce pathological responses and thereby improve survival. Rilvegostomig is a novel anti-TIGIT/anti-PD-1 bispecific antibody that is currently investigated in a Phase I/II clinical trial (ARTEMIDE-01, NCT04995523) for advanced or metastatic PD-L1-positive non-small cell lung cancer. The study provided promising preliminary evidence on the safety and efficacy of Rilvegostomig.5,6 Furthermore, a Phase III clinical trial (ARTEMIDE-Biliary01) using Rilvegostomig in combination with Capecitabine or Gemcitabine/Cisplatin or S-1 as adjuvant therapy for BTC after resection is underway. The efficacy of Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig as neoadjuvant treatment in resectable iCCA has yet to be established. This is a phase II, open-label multi-centre study to assess efficacy of Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig treatment in pre-surgical setting for upfront resectable iCCA, followed by adjuvant Gemcitabine/Cisplatin and Rilvegostomig. 40 patients are expected to enrol with resectable iCCA at three sites. Patients will receive prior to surgery: 2 cycles of combinational therapy with Gemcitabine (800mg) /Cisplatin (25mg) /Nab-Paclitaxel (100mg) and Rilvegostomig (Q3W). Post-surgical resection, adjuvant therapy will consist of 4 cycles of Gemcitabine (1000mg) /Cisplatin (25mg) and Rilvegostomig (Q3W). Rilvegostomig (Q3W) will be continued for a total of 12 months in the adjuvant phase. All participants will be followed for survival until the end of study. Dosing of Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig may be delayed per the trial management group's discretion but dose reduction will not be allowed. Toxicity management for Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig-related toxicity, including management of immune-mediated reactions, infusion-related reactions, and non-immune-mediated reactions will be provided in the Toxicity Management Guidelines

Conditions

• Cholangiocarcinoma Resectable

Interventions

Type	Name	Description
DRUG	Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig	: Patients will receive prior to surgery: 2 cycles of combinational therapy with Gemcitabine (800mg) /Cisplatin (25mg) /Nab-Paclitaxel (100mg) and Rilvegostomig (Q3W). Post-surgical resection, adjuvant therapy will consist of 4 cycles of Gemcitabine (1000mg) /Cisplatin (25mg) and Rilvegostomig (Q3W). Rilvegostomig (Q3W) will be continued for a total of 12 months in the adjuvant phase

Timeline

• Start date: 2024-12-15
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2024-08-26
• Last updated: 2024-08-26

Locations

1 site across 1 country: Canada