PURITY is a multicentre, randomized adaptive phase II/III trial aimed at comparing the triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment (ARM A) versus standard upfront surgery (ARM B) in terms of 12-month PFS rate (phase II part) and PFS (phase III part) in patients with resectable BTC at high risk for recurrence.
PURITY is a multicentre, randomized adaptive phase II/III trial aimed at comparing the triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment (ARM A) versus standard upfront surgery (ARM B) in terms of 12-month PFS rate (phase II part) and PFS (phase III part) in patients with resectable BTC at high risk for recurrence. High risk for recurrence, for which patients will be eligible for study, is defined by the presence of at least one of the following risk features, as evaluated at baseline (pre-surgery): 1. For cholangiocarcinoma: * Suspected or definite locoregional lymph node involvement in the absence of jaundice (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 MTD discussion (eg. short axis \> 1.5 cm, contrast enhancement uptake, round shape, restriction at DWI). * Macrovascular invasion at preoperative CT scan. * Expected R1 resection due to proximity to major intrahepatic vascular and biliary structures. * 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
300
◦ Gemcitabine 800 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles
◦ Nab-paclitaxel 100 mg/mq, day 1 and 8 of 21-day cycles, for 3 cycles
◦ Cisplatin 25 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles
Curative surgery on primary tumor
1250 mg/m2 given orally twice daily on days 1 to 14 of a 3 weekly cycle for a total of 8 cycles
Ospedali Riuniti di Ancona
Ancona, Italy
NOT_YET_RECRUITINGASST Papa Giovanni XXIII
Bergamo, Italy
NOT_YET_RECRUITINGOncologia Medica Policlinico Sant'Orsola - Malpighi
Bologna, Italy
NOT_YET_RECRUITINGASST Spedali Civili
Brescia, Italy
NOT_YET_RECRUITINGAzienda Ospedaliera S. Croce e Carle
Cuneo, Italy
NOT_YET_RECRUITINGIRST Dino Amadori
Meldola, Italy
NOT_YET_RECRUITINGFondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
RECRUITINGHumanitas Cancer Center
Milan, Italy
NOT_YET_RECRUITINGOspedale Niguarda Cancer Center
Milan, Italy
NOT_YET_RECRUITINGOspedale San Raffaele
Milan, Italy
NOT_YET_RECRUITING...and 9 more locations
12-month progression-free survival (PFS) rate
the proportion of patients alive and free from progression/post-resection recurrence by 12-months timepoint from randomization (to be considered as primary endpoint in the phase II part of the study and as secondary endpoint in the phase III part of the study).
Time frame: 12 months
median PFS
i.e. the time from randomization to disease progression, post-resection recurrence or death from any cause (to be considered as secondary endpoint in the phase II part of the study and as primary endpoint in the phase III part of the study).
Time frame: From date of randomization until the date of first documented progression (as assessed by radiological evaluation and clinical examination) or date of death from any cause, whichever came first, assessed up to 120 months
Median event free survival
i.e. the time from randomization to disease progression that precludes definitive surgery, treatment discontinuation for any reason, post-resection recurrence, a second primary cancer, or death from any cause.
Time frame: from date of randomization to disease progression that precludes definitive surgery, treatment discontinuation for any reason, post-resection recurrence, diagnosis of second cancer, or death from any cause, assessed up to 120 months
Median relapse free survival
i.e. the time from surgery to disease recurrence or death in patients who undergo to surgery with curative intent.
Time frame: from date of surgery to date of disease recurrence or date of death, whichever came first, in patients who undergo surgery with curative intent, assessed up to 120 months.
Median Overall survival
i.e. the time from randomization to death or last follow-up for alive patients.
Time frame: from date of randomization to date of death (or last follow up for alive patients), assessed up to 120 months.
R0 resection rate
i.e. the percentage of patients, relative to the total of randomized patients, for whom a R0 resection is achieved.
Time frame: At surgery
R0+R1 resection rate
i.e. the percentage of patients, relative to the total of randomized patients, for whom the tumor was macroscopically removed and the intent of surgery is considered curative.
Time frame: At surgery
Quality of life EORTC QLQ-C30 scores
QoL will be estimated with EORTC QLQ-C30; mean score changes from baseline, proportion of patients with improved, stable, or deteriorated scores from baseline and time to deterioration in the EORTC QLQ-C30 scores will be compared between the two arms. Time to deterioration will be defined as the time from baseline to the first onset of a 10-point or greater decrease (for functional scales)/increase (for symptoms scale) from baseline, with confirmation under the right-censoring rule. All available observations will be used to calculate time to deterioration.
Time frame: Quality of life questionnaires will be compiled during screening (28 days before randomisation) and at restaging before (week 8 to 10 after randomisation) and after surgery (week 6 to 16 after surgery)
Quality of life BIL21 scores
QoL will be estimated with the module BIL21; mean score changes from baseline, proportion of patients with improved, stable, or deteriorated scores from baseline and time to deterioration in the BIL21 physical functioning, social functioning, and fatigue scores will be compared between the two arms. Time to deterioration was defined as the time from baseline to the first onset of a 10-point or greater decrease from baseline for functional scales or a 10-point or greater increase for symptom scales, with confirmation under the right-censoring rule. All available observations will be used to calculate time to deterioration.
Time frame: Quality of life questionnaires will be compiled during screening (28 days before randomisation) and at restaging before (week 8 to 10 after randomisation) and after surgery (week 6 to 16 after surgery)
Overall response rate
of neoadjuvant therapy as per investigator assessment and central review, i.e. the percentage of patients, relative to the total of enrolled subjects receiving neoadjuvant treatment, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria.
Time frame: At radiological evaluation as performed at restaging before surgery (week 8 to 10 after randomisation)
Resectability rate of primary tumor
i.e. the retrospective evaluation of patients with unresectable disease, as assessed by the central review committee, in the two arms, and of the rate of conversion to resectability in the neoadjuvant arm.
Time frame: Resectability rate will be assessed before surgery (after the 3 cycles of neoadjuvant chemotherapy for the experimental treatment arm)
Toxicity rates
.e. the percentage of patients, relative to the total of subjects randomized to neoadjuvant treatment, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0).
Time frame: Through study completion, an average of 1 year for each patient
Perioperative morbidity and mortality
i.e. the percentage of patients, relative to the total of enrolled subjects undergoing surgery, with any serious perioperative morbidity or mortality according to Clavien-Dindo classification.
Time frame: At surgery
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