CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence

NCT06037980 | Recruiting Phase 2 DMC

• 1 other identifier: PURITY
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 19

Brief Summary

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.

Conditions

Biliary Tract Cancer; Cholangiocarcinoma

Keywords

Biliary Tract Cancers; Cholangiocarcinoma; Neoadjuvant Chemotherapy; Cisplatin Gemcitabine Nabpaclitaxel

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  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

Secondary Outcomes (11)

• Median event free survival

  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

  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

  from date of randomization to date of death (or last follow up for alive patients), assessed up to 120 months.

• R0 resection rate

  At surgery

• R0+R1 resection rate

  At surgery

Study Arms (2)

Preoperative chemotherapy

EXPERIMENTAL

Triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment followed by surgery and adjuvant chemotherapy

Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: Cisplatin; Procedure: Curative Surgery; Drug: Capecitabine

Upfront surgery

ACTIVE COMPARATOR

Standard upfront surgery and adjuvant chemotherapy

Procedure: Curative Surgery; Drug: Capecitabine

Interventions

Gemcitabine DRUG

◦ Gemcitabine 800 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles

Preoperative chemotherapy

Nab paclitaxel DRUG

◦ Nab-paclitaxel 100 mg/mq, day 1 and 8 of 21-day cycles, for 3 cycles

Also known as: Abraxane

Preoperative chemotherapy

Cisplatin DRUG

◦ Cisplatin 25 mg/mq iv, day 1 and 8 of 21-day cycles, for 3 cycles

Preoperative chemotherapy

Curative Surgery PROCEDURE

Curative surgery on primary tumor

Preoperative chemotherapy; Upfront surgery

Capecitabine DRUG

1250 mg/m2 given orally twice daily on days 1 to 14 of a 3 weekly cycle for a total of 8 cycles

Preoperative chemotherapy; Upfront surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures.
• Female and male patients ≥18 years and \<75 years.
• 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.
• Availability of a tumoral sample
• ECOG performance status of 0-1.
• No prior tumor resection for BTC.
• Technically resectable BTC as per local Multidisciplinary Team (MDT) assessment, including a core team with at least one medical oncologist, one surgeon, one radiologist, one endoscopist/gastroenterologist and one pathologist, all with expertise \> 3 years on biliary tract cancer and hepatobiliary oncology.
• High risk for recurrence defined as the presence of at least one of the following risk features, as evaluated at baseline (pre-surgery):
• 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 due to proximity to major intrahepatic vascular and biliary structures.

You may not qualify if:

• Known allergy or hypersensitivity to any of the study drugs.
• Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer.
• Locally unresectable tumor according to local MDT (including radiological evidence suggesting inability to resect with curative intent whilst maintaining adequate vascular inflow and outflow, and sufficient future liver remnant).
• Evidence of distant metastases at any site.
• 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.
• Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic decompensation in the year before enrolment.
• Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved HBV infection are eligible. Patients with chronic disease controlled by antiviral therapy or requiring prophylactic treatment are eligible.
• Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment.
• Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable per standard of care assay, and they must be compliant with antiretroviral treatment.
• Pregnant or breast-feeding patient, or patient is planning to become pregnant within 7 months after the end of treatment.
• Any other concurrent antineoplastic treatment including radiotherapy.
• Previous or concurrent systemic (eg cytotoxic or targeted or other experimental drugs) therapy for BTC.
• Prior surgery or locoregional therapy for BTC.
• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last three months, significant arrhythmia).
• Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent.

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (19)

Ospedali Riuniti di Ancona

Ancona, Italy

NOT YET RECRUITING

ASST Papa Giovanni XXIII

Bergamo, Italy

NOT YET RECRUITING

Oncologia Medica Policlinico Sant'Orsola - Malpighi

Bologna, Italy

NOT YET RECRUITING

ASST Spedali Civili

Brescia, Italy

NOT YET RECRUITING

Azienda Ospedaliera S. Croce e Carle

Cuneo, Italy

NOT YET RECRUITING

IRST Dino Amadori

Meldola, Italy

NOT YET RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Humanitas Cancer Center

Milan, Italy

NOT YET RECRUITING

Ospedale Niguarda Cancer Center

Milan, Italy

NOT YET RECRUITING

Ospedale San Raffaele

Milan, Italy

NOT YET RECRUITING

Università di Modena

Modena, Italy

NOT YET RECRUITING

Ospedale S. Gerardo

Monza, Italy

NOT YET RECRUITING

IOV

Padua, Italy

NOT YET RECRUITING

Policlinico San Matteo

Pavia, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Pisa

Pisa, Italy

RECRUITING

IRST (Cesena-Forlì-Meldola)

Ravenna, Italy

NOT YET RECRUITING

Policlinico Gemelli

Rome, Italy

NOT YET RECRUITING

Azienda Ospedaliera Ordine Mauriziano

Turin, Italy

NOT YET RECRUITING

AOUI Verona - Policlinico "G.B. Rossi"

Verona, Italy

NOT YET RECRUITING

Related Publications (4)

• Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis. Eur J Surg Oncol. 2019 Aug;45(8):1432-1438. doi: 10.1016/j.ejso.2019.03.023. Epub 2019 Mar 21.

  PMID: 30914290 RESULT

• Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, Raghav KPS, Iwasaki M, Masci P, Ramanathan RK, Ahn DH, Bekaii-Saab TS, Borad MJ. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):824-830. doi: 10.1001/jamaoncol.2019.0270.

  PMID: 30998813 RESULT

• Maithel SK, Keilson JM, Cao HST, Rupji M, Mahipal A, Lin BS, Javle MM, Cleary SP, Akce M, Switchenko JM, Rocha FG. NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2023 Oct;30(11):6558-6566. doi: 10.1245/s10434-023-13809-5. Epub 2023 Jun 27.

  PMID: 37368098 RESULT

• Niger M, Nichetti F, Fornaro L, Pircher C, Morano F, Palermo F, Rimassa L, Pressiani T, Berardi R, Gardini AC, Sperti E, Salvatore L, Melisi D, Bergamo F, Siena S, Mosconi S, Longarini R, Arcangeli G, Corallo S, Delliponti L, Tamberi S, Fea E, Brandi G, Rapposelli IG, Salati M, Baili P, Miceli R, Ljevar S, Cavallo I, Sottotetti E, Martinetti A, Busset MDD, Sposito C, Di Bartolomeo M, Pietrantonio F, de Braud F, Mazzaferro V. A phase II/III randomized clinical trial of CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative chemotherapy versus immediate resection in patIents with resecTable BiliarY Tract Cancers (BTC) at high risk for recurrence: PURITY study. BMC Cancer. 2024 Apr 8;24(1):436. doi: 10.1186/s12885-024-12225-6.

  PMID: 38589856 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma

Interventions

Gemcitabine; Taxes; Albumin-Bound Paclitaxel; Cisplatin; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Monica Niger, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

• Monica Niger, MD

  02 2390 2919

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Niger, MD

CONTACT

02 2390 2919; monica.niger@istitutotumori.mi.it

Federico Nichetti, MD

CONTACT

02 2390 3586; PURITYstudy@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, open-label, multicenter, randomized phase II-III study

Study Record Dates

• First Submitted: August 9, 2023
• First Posted: September 14, 2023
• Study Start: November 7, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (19)