PURITY

Biliary tract cancers (BTCs) are rare and highly lethal cancers, with a 5-year survival inferior to 20%1-3. The only potential curative treatment is surgical resection. However, despite the high surgical effort, the 5-year survival rate after radical surgery (R0) is 20-40% and recurrence rates are up to ~75%4-6. Overall, up to ~40% of patients relapse within 12 months after resection, and half of these patient will recur systemically4-6. Currently, there is no standard of care or prospective data for neoadjuvant chemotherapy in resectable BTC, but retrospective reports suggest the potential benefit of a pre-operative treatment8,9.

Key Inclusion criteria

1. Female and male patients ≥18 years and <75 years, ECOG PS 0-1.
2. Histologically or cytologically confirmed non metastatic resectable carcinoma of biliary tract (BTC), including gallbladder carcinoma (GBC), intrahepatic, periperihilar or distal Cholangiocarcinoma (CCA). Mixed tumor entities with hepatocellular carcinoma and ampullary cancers are excluded.
3. Availability of a tumoral sample
4. No prior tumor resection for BTC.
5. Technically resectable BTC as per local Multidisciplinary Team (MDT) assessment
6. High risk for recurrence defined as the presence of at least one of the following at baseline:
   1. For cholangiocarcinoma:
      • Suspected or definite locoregional lymph node involvement (at least one of the following):
        • positive FNA cytology (obtained by EUS).
        • positive locoregional lymph nodes at PET-CT.
        • suspected positive locoregional lymph nodes at imaging (CT or MRI scan) according to local MDT discussion (eg. short axis > 1.5 cm, contrast enhancement uptake, round shape, restriction at DWI).
      • Macrovascular invasion at preoperative CT scan.
      • Expected R1 resection
      • For iCCA, presence of satellitosis or multifocal disease or radiological suspicion of tumoral diaphragmatic adhesion.
      • For iCCA, size of the liver lesion >5 cm.
      • For eCCA, size of the primary lesion > 3cm.
      • Ca19.9 >100 U/mL.
   2. For GBC:
      • Incidentally Detected Gallbladder Carcinoma (IGBC) after simple cholecystectomy with indication for radical second surgery (>pT2) or newly diagnosed GBC.
7. Adequate baseline hematologic, liver, renal and coagulation function

Key Exclusion criteria

1. Tumors requiring multi-step surgical procedures such as two-stage hepatectomy or Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) due to liver volumetry-based assessment of anticipated inadequate future liver remnant.
2. Child-Pugh B (or worse) cirrhosis or cirrhosis (any degree) and a history of hepatic decompensation in the year before enrolment.
3. Know active uncontrolled hepatitis B or hepatitis C.
4. Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment.
5. Known uncontrolled HIV infection.
6. Severe or uncontrolled cardiovascular disease or psychiatric disorder or any serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial

PURITY is a no-profit, multicentre, randomized adaptive phase II/III trial aimed at improving clinical practice by evaluating the efficacy of the combination of gemcitabine, cisplatin and nabpaclitaxel (GAP) as neoadjuvant treatment in patients with resectable BTC at high risk for recurrence.

Primary endpoint:
12-month progression-free survival (PFS) rate

Key secondary endpoints:
Progression Free Survival (PFS), Event Free Survival (EFS), Recurrence Free Survival (RFS), Overall Survival (OS), R0/R0+R1 resection rate, safety, QoL