## Protocol Section
### Identification Module
**NCT ID:** NCT02959879

**Acronym:** PANACHE01

**Brief Title:** Neo-adjuvant FOLF(IRIN)OX for Resectable Pancreatic Adenocarcinoma

**Official Title:** Resectable Pancreatic Adenocarcinoma Neo-Adjuvant FOLF(IRIN)OX-based CHEmotherapy - A Multicenter, Randomised Phase II Trial (PANACHE01-PRODIGE48 Study)

#### Organization Study ID Info
**ID:** 2014/210/HP
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Rouen
### Status Module
#### Completion Date
**Date:** 2021-12

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2018-04-26

**Type:** ACTUAL

**Last Update Submit Date:** 2018-04-24

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2021-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2017-03-01

**Type:** ACTUAL

**Status Verified Date:** 2018-04

#### Study First Post Date
**Date:** 2016-11-09
**Type:** ESTIMATED
**Study First Submit Date:** 2016-11-03
**Study First Submit QC Date:** 2016-11-07
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** UNICANCER

**Class:** OTHER

**Name:** Federation Francophone de Cancerologie Digestive

**Class:** OTHER

**Name:** Federation of Research in Surgery (FRENCH)

**Class:** OTHER

**Name:** GERCOR - Multidisciplinary Oncology Cooperative Group

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Rouen

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** In patients with resectable pancreatic duct adenocarcinoma (PDAC), curative surgery followed by adjuvant chemotherapy is currently the standard of care. However, the long-term results are still poor, with median disease-free and overall survival of 14 months and 23 months. The corresponding 5-year overall survival rate is 20%.

Chemotherapy before surgery (neoadjuvant chemotherapy) allows identification of patients with rapidly progressive metastatic disease at time of preoperative restaging (surgery is then avoided in these patients), and may increase the rate of free margin resection (R0) and reduce the risk of local recurrence.

Even though single-agent gemcitabine and 5-FU have been validated in adjuvant and metastatic settings, the objective response was low (at around 10%), whereas combination chemotherapy exceeds a response rate of 30% in advanced disease. In metastatic PDAC, palliative FOLFIRINOX chemotherapy has been demonstrated to be effective (in terms of response rates and progression-free survival) and well tolerated. Interestingly, the response rate is increased by using more than two chemotherapeutic agents in advanced pancreatic cancer, justifying the use of an alternative neoadjuvant FOLFOX-based chemotherapy arm.

PANACHE-01 is an open, non-comparative, randomised, multicentre Phase II study designed to assess the safety and efficacy of two modes of neo-adjuvant chemotherapy (FOLFIRINOX \& FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) for resectable PDAC.

Patients with immediately resectable PDAC (definition based on the NCCN's (American National Comprehensive Cancer Network 2014) latest guidelines) will be randomised to either pancreatectomy and adjuvant chemotherapy or 4 cycles of neoadjuvant chemotherapy with either FOLFOX or FOLFIRINOX. The patients in the neoadjuvant chemotherapy arms will receive postoperative chemotherapy for 4 months (8 cycles).

### Conditions Module

**Conditions:**

- Resectable Pancreatic Duct Adenocarcinoma

**Keywords:**

- FOLFOX

- FOLFIRINOX

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 160

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 4 cycles of FOLFOX neoadjuvant chemotherapy are administrated to patient. Curative surgery for resectable pancreatic duct adenocarcinoma will be done after neoadjuvant chemotherapy. 8 cycles of adjuvant chemotherapy are administrated following the surgery

**Intervention Names:**

- Drug: FOLFOX neoadjuvant chemotherapy

- Procedure: curative surgery for resectable pancreatic duct adenocarcinoma

- Drug: adjuvant chemotherapy

**Label:** FOLFOX neoadjuvant chemotherapy

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 4 cycles of FOLFIRINOX neoadjuvant chemotherapy are administrated to patient. Curative surgery for resectable pancreatic duct adenocarcinoma will be done after neoadjuvant chemotherapy. 8 cycles of adjuvant chemotherapy are administrated following the surgery

**Intervention Names:**

- Drug: FOLFIRINOX neoadjuvant chemotherapy

- Procedure: curative surgery for resectable pancreatic duct adenocarcinoma

- Drug: adjuvant chemotherapy

**Label:** FOLFIRINOX neoadjuvant chemotherapy

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Curative surgery for resectable pancreatic duct adenocarcinoma will be done after randomization.

12 cycles of standard adjuvant chemotherapy are administrated following the surgery

**Intervention Names:**

- Procedure: curative surgery for resectable pancreatic duct adenocarcinoma

- Drug: Standard adjuvant chemotherapy

**Label:** standard adjuvant chemotherapy

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- FOLFOX neoadjuvant chemotherapy

**Description:** 4 cycles of FOLFOX neoadjuvant chemotherapy are administrated to patient

**Name:** FOLFOX neoadjuvant chemotherapy

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- FOLFIRINOX neoadjuvant chemotherapy

**Description:** 4 cycles of FOLFIRINOX neoadjuvant chemotherapy are administrated to patient

**Name:** FOLFIRINOX neoadjuvant chemotherapy

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- FOLFIRINOX neoadjuvant chemotherapy

- FOLFOX neoadjuvant chemotherapy

- standard adjuvant chemotherapy

**Description:** curative surgery for resectable pancreatic duct adenocarcinoma

**Name:** curative surgery for resectable pancreatic duct adenocarcinoma

**Type:** PROCEDURE

#### Intervention 4

**Arm Group Labels:**

- standard adjuvant chemotherapy

**Description:** 12 cycles of standard adjuvant chemotherapy are administrated

**Name:** Standard adjuvant chemotherapy

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- FOLFIRINOX neoadjuvant chemotherapy

- FOLFOX neoadjuvant chemotherapy

**Description:** 8 cycles of standard adjuvant chemotherapy are administrated

**Name:** adjuvant chemotherapy

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Number of patients alive is evaluated 12 months after the surgery

**Measure:** Number of patients alive

**Time Frame:** 12 months

**Description:** The number of patients who achieved the complete chemotherapy treatment sequences is evaluated 12 months after the surgery

**Measure:** Number of patients who achieved the complete chemotherapy treatment sequences

**Time Frame:** 12 months

#### Secondary Outcomes

**Description:** Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

**Measure:** Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

**Time Frame:** through end of treatment, an average of 12 months

**Description:** Evaluation of post-operative complications is assessed using Dindo Clavien classification

**Measure:** Number of post-operative complications

**Time Frame:** 1 month after surgery

**Description:** Number of patients alive is evaluated 36 months after the surgery

**Measure:** Number of patients alive and without recurrence

**Time Frame:** 36 months

**Description:** Number of accomplished R0 resection surgery is evaluated by pathologists

**Measure:** Number of accomplished R0 resection surgery

**Time Frame:** Surgery day

**Description:** Evaluation of quality of life is done using EORTC QLQ C30

**Measure:** Evaluation of quality of life

**Time Frame:** 4 weeks after the end of chemotherapy treatment

**Description:** Evaluation of quality of life is done using EORTC QLQ-PAN26

**Measure:** Evaluation of quality of life

**Time Frame:** 4 weeks after the end of chemotherapy treatment

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Histology-proven, adenocarcinoma of the pancreas.
* Resectable adenocarcinoma (according to the NCCN classification 2014): absence of distant organ or distal lymph node metastases, absence of evidence of superior mesenteric vein (SMV) and portal vein distortion, tumour thrombus, or venous encasement, the existence of clear fat planes around the celiac axis, hepatic artery and superior mesenteric artery (SMA). Resectability is evaluated on arterial-phase and portal-phase IV contrast-enhanced multislice CT-scan of the pancreas (slice thickness: 2.5 mm), as evaluated in a multidisciplinary staff meeting including at least one radiologist and one expert surgeon.
* No prior chemotherapy.
* Age 18 years or over.
* Ability to understand and willingness to consent to formal requirements for study participation
* Provision of written informed consent prior to any study-specific screening procedures.

Exclusion Criteria:

* PDAC defined as "borderline", locally advanced, non-resectable or metastatic.
* Prior cancer therapy for PDAC
* Surgical or anaesthesiological contra-indications: non-controlled congestive heart failure - non-treated angina - recent myocardial infarction (in the previous year) - non-controlled arterial hypertension (SBP \>160 mm or DBP \> 100 mm, despite optimal drug treatment), long QT, major non-controlled infection, severe liver failure.
* Any medical, psychological or social situation that (in the investigator's opinion) could limit (i) the patient's compliance with the protocol or (ii) the ability to obtain or interpret data.
* Pregnant or breastfeeding women and women of child-bearing age not using effective means of contraception.
* History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1, according to according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.0.
* Known hypersensitivity reaction to any of the components of study treatments.
* Pregnancy (the absence of which must be confirmed in a ß-hCG test) or breast-feeding.
* Any significant disease which, in the investigator's opinion, would exclude the patient from the study.
* Patients having been included in a clinical trial within the previous 4 weeks or participating in another trial.

**Maximum Age:** 85 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** lilian.schwarz@chu-rouen.fr

**Name:** Lilian SCHWARZ, MD

**Phone:** +3323288

**Phone Ext:** 8265

**Role:** CONTACT

**Contact 2:**

**Email:** julien.blot@chu-rouen.fr

**Name:** Julien BLOT

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Rouen

**Contacts:**

***Contact 1:***

- **Name:** Lilian SCHWARZ, MD

- **Role:** CONTACT

***Contact 2:***

- **Name:** Lilian SCHWARZ, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** France

**Facility:** Rouen University Hospital

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** Rouen University Hospital

**Name:** Lilian SCHWARZ, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Schwarz L, Vernerey D, Bachet JB, Tuech JJ, Portales F, Michel P, Cunha AS. Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study). BMC Cancer. 2018 Jul 24;18(1):762. doi: 10.1186/s12885-018-4663-4. Erratum In: BMC Cancer. 2020 Mar 3;20(1):168.

**PMID:** 30041614

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000002277

- Term: Carcinoma

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000018299

- Term: Neoplasms, Ductal, Lobular, and Medullary

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M25356

- Name: Carcinoma, Ductal

- Relevance: HIGH

- As Found: Duct Adenocarcinoma

- ID: M3585

- Name: Adenocarcinoma

- Relevance: HIGH

- As Found: Adenocarcinoma

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000044584

- Term: Carcinoma, Ductal

### Intervention Browse Module - Ancestors

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M271136

- Name: Folfirinox

- Relevance: HIGH

- As Found: Indocyanine Green

### Intervention Browse Module - Meshes

- ID: C000627770

- Term: Folfirinox

### Misc Info Module

- Version Holder: 2024-05-24
