Neoadjuvant mFolfirinox With or Without Preoperative Concomitant Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Carcinoma (PANDAS-PRODIGE 44)

Pancreatic Carcinoma Clinical Trial

Official title:

Two Arm, Prospective, Multicenter Randomized Phase II Trial of Neoadjuvant Modified Folfirinox Regimen, With or Without Preoperative Concomitant Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02676349
• Other study ID #: 2014-005681-29
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 13, 2016
• Est. completion date: October 2027

Study information

• Verified date: September 2023
• Source: Institut de Cancérologie de Lorraine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, randomized phase II trial. The aim of this study is to assess the efficacy of two therapeutics strategies. Patients with borderline-resectable pancreatic cancer (BRPC) will be randomly in two arms : neoadjuvant mFolfirinox followed with or without preoperative chemoradiotherapy with capecitabine.

Description:

Surgery, especially if followed by adjuvant chemotherapy, offers the only chance of cure of pancreatic cancer. At first diagnosis, after careful assessment, only 10 to 15% of patients are considered to be candidates for surgical resection and about 7% have a potentially resectable disease. These potentially resectable tumors called "borderline resectable pancreatic cancer" (BRPC) are conceptualized as those that involve the mesenteric vasculature to a limited extent and those for which resection, while possible, would likely be compromised by positive surgical margins (R1) in the absence of neoadjuvant treatment. R0 resection is indeed considered as an independent prognostic factor for survival when the surgical procedures, histological examination and definition of microscopic invasion are standardized.

The objectives of neoadjuvant treatments of BRPC is to reduce tumor volume before surgery in order to improve the chances of radical (R0) resection and to reduce the rate of lymph node positivity and recurrences. The primary outcome in published studies is usually R0 resection rate, but these results also depend on the number of margins examined and the definition of microscopic margin involvement. Prospective studies with consistent selection criteria and standardized assessment criteria are needed.

Different neoadjuvant therapeutic strategies have been tested in pilot studies: preoperative chemoradiotherapy or neoadjuvant chemotherapy, followed or not by a preoperative (chemo)radiotherapy. Due to the lack of randomized studies, the best sequence of treatment administration has not been established.

The aim of this prospective, randomized, multicenter, trial is to evaluate the R0 resection rate with neoadjuvant Folfirinox, followed or not by radiochemotherapy for patients with borderline resectable pancreatic cancers.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: October 2027
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• ECOG performance status 0 or 1

• Adult patients = 18 years and = 75 years of age

• Histologic or cytologic proven adenocarcinoma of the pancreas (histologic confirmation of diagnosis is preferred)

• Confirmation by independent multidisciplinary expert review of borderline resectable status, according to NCCN-Clinical Practice Guidelines in Oncology "pancreatic adenocarcinoma", version 1.2015.

• Adequate hematologic function, as follows:

• absolute neutrophil count (ANC) = > 2000/mm3

• platelet count = 100 000/mm3

• haemoglobin = 10 g/dL

• Adequate renal, hepatic and bone marrow function, defined as:

• Calculated creatinine clearance = 50 mL/min according to MDRD formula

• Serum total bilirubin = 1.5 times the institutional upper limit of normal. Patients with a biliary short metal stent due to cancer obstruction may be included provided that high-quality imaging is performed before stenting and bilirubin level after stent insertion decreased to = 20 mg/L (= 34 µmol/l), and there is no cholangitis.

• Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner)

• for male subject: during the treatment and for up to 6 months after the last dose of oxaliplatin or up to 3 months after the last dose of irinotcan.

• for female subject: during the treatment and for up to 4 months after the last dose of oxaliplatin or up to 3 months after the last dose of irinotcan.

• Ability to provide written informed consent before the start of any study specific procedures

• Patient's legal capacity to consent to study participation and to understand and comply with the requirements of the study.

Exclusion Criteria:

• Any previous treatment of the pancreatic cancer except biliary short metal stenting (chemotherapy, targeted tumor therapy, local ablative therapy, previous irradiation within the actual fields of planned radiotherapy)

• Evidence of distant metastases including ascites

• Evidence of extent of pancreatic cancer beyond that defined as "borderline resectable" : suspicious lymphadenopathy outside of the standard field of resection (i.e., aortocaval nodes, distant abdominal nodes)

• Contraindication for pancreas resection

• Pregnant or breast feeding females

• Patients with known Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism

• Uracilemia = 16ng/mL either a partial or complete deficiency in dihydropyrimidine dehydrogenase (DPD)

• Participation in any other clinical trial or treatment with any experimental drug within 28 days before enrolment to the study or during study participation until the end of treatment visit that can be interfering with the objectives of the study

• Previous or concurrent malignant tumor disease other than underlying tumor disease (with the exception of cervical cancer in situ, adequately treated non-melanoma skin cancers, superficial bladder tumors (Ta, Tis, and T1) or any curatively treated without chemotherapy and favourable prognosis tumors without evidence of disease for > 3 years prior to enrolment)

• Any severe and/or uncontrolled medical conditions including but not limited to:

• Clinically significant cardiovascular or vascular disease : angina pectoris (even controlled), previous myocardial infarction, serious uncontrolled cardiac arrhythmia, chronic heart failure, acute or chronic infectious disease requiring general treatment)

• Acute and chronic, active infectious disorders that requires systemic treatment

• Peripheral polyneuropathy > grade 1

• Any previous inflammatory disease of colon or rectum

• Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the study and his/her safety during the study e.g. severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders

• Uncorrected disturbed electrolyte balance, in particular hypokalemia or hypocalcemia

• Hypersensitivity against any of the study drugs (gemcitabine, oxaliplatin, irinotecan, 5-fluorouracil, folinic acid), or the ingredients of these drugs (e.g. fructose).

Related Conditions & MeSH terms

• Carcinoma
• Pancreatic Carcinoma
• Pancreatic Neoplasms

Intervention

Drug:
• mFolfirinox
oxaliplatin folinic acid irinotecan 5FU oxaliplatin

Radiation:
• Chemoradiotherapy
conformational external irradiation (50.4 Gy) + capecitabine

Procedure:
• surgery
1 to 4 weeks after neoadjuvant treatment according to tumour response

Drug:
• Adjuvant chemotherapy
Gemcitabine or modified LV5FU (folinic acid+-bolus fluorouracil+ infusional fluorouracil)

Locations

Country	Name	City	State
France	Institut Bergonié	Bordeaux
France	Polyclinique Bordeaux Nord	Bordeaux
France	Hôpital Beaujon	Clichy
France	Chu Colmar	Colmar
France	Hôpital Henri Mondor (APHP)	Creteil
France	Centre Oscar Lambret	Lille
France	Chru Lille	Lille
France	Infirmerie Protestante de Lyon	Lyon
France	Hôpital Européen Marseille	Marseille
France	Hôpital La Timone	Marseille
France	Institut Paoli CALMETTES	Marseille
France	Institut du Cancer de Montpellier	Montpellier
France	Chu Nantes	Nantes
France	Hôpital Cochin (APHP)	Paris
France	Institut Mutualiste Montsouris	Paris
France	Pitié Salpêtrière (APHP)	Paris
France	Hôpital Haut-Lévêque	Pessac
France	CHU Reims	Reims
France	Centre Eugène Marquis	Rennes
France	Chu Rouen	Rouen
France	CHP Saint Grégoire	Saint Grégoire
France	Institut de Cancérologie de l'Ouest	Saint-Herblain
France	Chru Tours	Tours
France	Chru Nancy	Vandoeuvre-les-nancy
France	Institut de Cancérologie de Lorraine	Vandoeuvre-les-nancy
France	Hôpital Paul Brousse	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Cancérologie de Lorraine

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the efficacy of two neoadjuvant therapies in patients with borderline resectable pancreatic carcinoma evaluated on histological R0 resection margin rate		up to 7.5 months
Secondary	Evaluate the toxicities associated with chemotherapy and chemoradiotherapy		up to 7 years
Secondary	Evaluate the proportion of resected patients		up to 7.5 months
Secondary	Evaluate the response rate to chemotherapy and chemoradiotherapy		up to 7.5 months
Secondary	Evaluate the histological complete response rate in resected patients.		up to 7.5 months
Secondary	Evaluate the perioperative mortality rate		up to 8.5 months
Secondary	Evaluate the perioperative morbidity rate		up to 8.5 months
Secondary	Evaluate the overall survival		up to 7 years
Secondary	Evaluate the quality of life		up to 7.5 months
Secondary	Evaluate the loco-regional relapse-free survival		7 years
Secondary	Evaluate the metastatic Progression Free Survival		7 years
Secondary	Evaluate the progression-free survival		7 years